atrial-natriuretic-factor and Kidney-Failure--Chronic

Patients with advanced chronic kidney disease are at a high risk of cardiovascular events. Patients with end-stage renal disease have a particularly high morbidity and mortality, in part attributed to the complications and dysfunction related to vascular access in this population. Creation of an arteriovenous access for HD is considered standard of care for most patients and has distinct advantages including less likelihood of infections, less need for intervention, and positive impact on survival as compared with usage of a catheter. However, creation of an arteriovenous shunt incites a series of events that significantly impacts cardiovascular and neurohormonal health in both positive and negative ways. This article will review the short- and long-term effects of dialysis access on cardiovascular, neurohormonal, and pulmonary systems as well as a brief review of their effect on survival on HD. Presence of other comorbidities in a patient with dialysis access can amplify these effects, and these considerations are of paramount importance in individualizing the approach to not only the choice of vascular access but also the modality of kidney replacement therapy.

Topics: Arteriovenous Shunt, Surgical; Atrial Natriuretic Factor; Blood Pressure; Blood Volume; Cardiac Output; Cardiovascular Diseases; Comorbidity; Heart Failure; Heart Rate; Humans; Kidney Failure, Chronic; Natriuretic Peptide, Brain; Renal Dialysis; Vascular Resistance

Topics: Atrial Natriuretic Factor; Cost-Benefit Analysis; Disease Progression; Humans; Kidney Failure, Chronic; Kidney Transplantation; Natriuretic Peptide, Brain; Oximetry; Polysomnography; Positive-Pressure Respiration; Sleep Apnea, Obstructive; Sleep Stages; Treatment Outcome

Natriuretic peptides (NPs) are released from the heart in response to pressure and volume overload. B-type natriuretic peptide (BNP) and N-terminal-proBNP have become important diagnostic tools for assessing patients who present acutely with dyspnea. The NP level reflects a compilation of systolic and diastolic function as well as right ventricular and valvular function. Studies suggest that using NPs in the emergency department can reduce the consumption of hospital resources and can lower costs by either eliminating the need for other, more expensive tests or by establishing an alternative diagnosis that does not require hospital stay. Caveats such as body mass index and renal function must be taken into account when analyzing NP levels. Natriuretic peptide levels have important prognostic value in multiple clinical settings, including in patients with stable coronary artery disease and with acute coronary syndromes. In patients with decompensated heart failure due to volume overload, a treatment-induced drop in wedge pressure is often accompanied by a rapid drop in NP levels. Knowing a patient's NP levels might thus assist with hemodynamic assessment and subsequent treatment titration. Monitoring NP levels in the outpatient setting might also improve patient care and outcomes.

Topics: Atrial Natriuretic Factor; Cardiovascular Diseases; Death, Sudden, Cardiac; Heart Diseases; Heart Failure; Hemodynamics; Humans; Kidney Failure, Chronic; Monitoring, Physiologic; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Obesity; Peptide Fragments; Prognosis; Pulmonary Edema; Pulmonary Embolism; Pulmonary Wedge Pressure; Renal Dialysis; Stroke; Weight Loss

Natriuretic peptides are involved in the regulation of volume homeostasis. Their levels generally are increased in the setting of volume expansion and act on multiple effector systems to cause vasodilation and natriuresis in an effort to return volume status back to normal. In patients with end-stage renal disease, the natriuretic capabilities of these peptides are limited. However, there has been much interest in the potential applicability of measurement of these peptides as a surrogate marker of volume status and in the determination of dry weight. Furthermore, atrial natriuretic peptide and brain natriuretic peptide can serve as markers of left ventricular dysfunction and may have utility in determining cardiac prognosis in patients on long-term dialysis therapy.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Blood Volume; Body Weight; Cohort Studies; Heart Failure; Humans; Kidney; Kidney Failure, Chronic; Natriuresis; Natriuretic Peptide, Brain; Natriuretic Peptides; Peritoneal Dialysis; Prognosis; Rats; Receptors, Neuropeptide; Ventricular Dysfunction, Left; Water-Electrolyte Balance

Topics: Atrial Natriuretic Factor; Biomarkers; Diagnostic Techniques, Endocrine; Heart Failure; Humans; Hypertension; Hyperthyroidism; Immunoradiometric Assay; Kidney Failure, Chronic; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Reference Values; Specimen Handling; Tachycardia, Supraventricular

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Humans; Kidney Failure, Chronic; Nephrotic Syndrome; Prognosis; Renal Dialysis; Renin-Angiotensin System

Patients with end-stage renal disease have a deranged sodium and water homeostasis leading to chronic volume overload. Atrial natriuretic peptides (ANPs) are circulating hormones that are involved in the regulation of volume homeostasis, blood pressure control, and electrolyte balance. In hemodialysis patients plasma ANPs are highly elevated and decrease during the dialysis session when fluid is removed. However, hemodialysis treatment never corrects the defect in the metabolism of these peptides and their circulating concentrations do not return to levels found in healthy controls. Besides uremia and chronic volume overload, other factors such as cardiac dysfunction or hypertension may contribute to the elevated plasma concentrations of ANPs. ProANP fragments which derive from the N-terminus of the ANP prohormone have been also found in the circulation and they have biological functions similar to alpha-ANP (ie, the C-terminus of the prohormone). The proANP peptides proANP(1-30), proANP(31-67), and proANP(1-98) are increased in patients undergoing regular hemodialysis treatment, but their decrease during the dialysis procedure is less pronounced than for alpha-ANP or cyclic GMP. Cellulose triacetate dialyzer membrane material lowered the plasma concentrations of proANP(1-30), proANP(31-67), and proANP(1-98) significantly more than polysulfone, whereas alpha-ANP and cyclic GMP were not differently affected. Aside from a variety of factors that influence circulating natriuretic factors in the uremic patient, there is evidence for differences in dialyzer membrane adsorption of these peptides which speculatively may be linked to dialysis-associated symptoms.

Topics: Adsorption; Atrial Natriuretic Factor; Humans; Kidney; Kidney Failure, Chronic; Plasma Volume; Renal Dialysis; Uremia

Topics: Atrial Natriuretic Factor; Blood Pressure; Blood Volume; Body Composition; Cyclic GMP; Electric Impedance; Extracellular Space; Humans; Kidney Failure, Chronic; Renal Dialysis; Ultrasonography; Vena Cava, Inferior

Cyclic GMP mediates regulation of the basic functions in the kidney. The membrane- and cytosolic (soluble) guanylate cyclase systems in the kidney glomeruli modulate reciprocally their activities. In physiological conditions, this compensatory regulation results in maintaining the stable cGMP level.

Topics: Animals; Atrial Natriuretic Factor; Cyclic GMP; Down-Regulation; Guanylate Cyclase; Humans; Kidney Failure, Chronic; Kidney Glomerulus; Signal Transduction

Sodium balance in patients with renal failure varies with the severity and clinical manifestations of renal disease. Progressive chronic renal insufficiency is typified by an adaptive increase in the sodium excretion rate per nephron as the total glomerular filtration rate declines. This increase is caused, at least in part, by the effect of atrial natriuretic peptide and other natriuretic peptides, whose release is augmented in the setting of volume expansion and renal failure. However, exogenous administration of natriuretic peptides in clinical chronic and acute renal disease does not consistently increase renal sodium excretion. As the glomerular filtration rate progressively declines towards end-stage renal disease, total renal sodium excretion eventually decreases, and extracellular volume expansion, hypertension, and edema develop. Sodium removal, induced by high dose diuretics or via convective ultrafiltration during dialysis, is necessary to decrease the extracellular volume to normal.

Topics: Acute Kidney Injury; Animals; Atrial Natriuretic Factor; Diuretics; Edema; Glomerular Filtration Rate; Humans; Hypertension; Kidney Failure, Chronic; Renal Dialysis; Sodium

In recent years, different clinical studies have provided new information on the pathophysiological role and diuretic effectiveness of atrial natriuretic peptide (ANP) in subjects with normal renal function and patients with chronic renal disease. Plasma ANP (pANP) was increased by infusion at the lowest doses ever tested in humans who were on low salt diet to the levels that the same subjects gained when on a normal salt diet; ANP accounted for at least 40% of the increase of natriuresis. Similarly, ANP appeared to be mainly involved in the physiological down-regulation of salt excretion (that is, during the shift from a normal to low-sodium diet). Interestingly, data have been also attained on the efficacy of ANP as diuretic agent when administered at a low nonhypotensive dosage in normals as well as CRF patients. Indeed, low-dose ANP promoted a marked increase of sodium excretion in CRF patients to the same levels observed in normals, likely because the renal patients exhibited a more marked pANP increment secondary to the lower renal catabolism of the infused hormone. Moreover, aldosterone suppression was greater in CRF patients with respect to normals. Furthermore, the fractional urinary excretion of cGMP increased more in CRF patients than in normals. Finally, ANP infusion augmented the urinary losses of the main solutes retained in CRF (urea, potassium, phosphorous) with a significant decrease in the plasma levels. Hence, ANP per se not only plays a significant role in the up- and down-regulation of sodium excretion in healthy state and chronic renal disease, but it may also be considered to be a powerful and unique diuretic agent in CRF at nonhypotensive dosages.

Topics: Animals; Atrial Natriuretic Factor; Diuretics; Humans; Kidney Failure, Chronic; Sodium

A host of abnormalities of renal structure and function accompanies advancing age. An appreciation of methodologic considerations, including population selection, that might confound the assessment of the effects of aging on renal function has prompted a recent reappraisal. Earlier studies assessed the effects of aging by utilizing cross-sectional studies and institutionalized elderly subjects, with their attendant drawbacks. Recent longitudinal studies have utilized appropriate patient cohorts, selected for lock of renal disease, including potential kidney transplant donors. These studies indicate that the morphological and functional changes of aging tend to be less marked than previously thought. The common denominator of these functional changes is a diminution in renal reserve, along with constraints on the kidney's ability to respond appropriately to challenges of either excesses or deficits. Although these alterations are unlikely to be of major clinical consequence under everyday conditions, they attain clinical significance when residual renal function is challenged by the superimposition of an acute illness. Finally, it should be emphasized that elderly patients frequently suffer from comorbid conditions, such as hypertension and heart disease, that may be additive to the changes of aging, thereby amplifying these abnormalities.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aging; Animals; Atrial Natriuretic Factor; Comorbidity; Creatinine; Cross-Sectional Studies; Epidemiologic Methods; Female; Glomerular Filtration Rate; Humans; Kidney; Kidney Failure, Chronic; Kidney Function Tests; Kidney Transplantation; Male; Middle Aged; Natriuresis; Potassium; Renal Circulation; Renal Dialysis; Renin-Angiotensin System; Tissue Donors; Water-Electrolyte Balance

Topics: Atrial Natriuretic Factor; Calcium Channel Blockers; Contrast Media; Endothelin Receptor Antagonists; Hemofiltration; Humans; Kidney Diseases; Kidney Failure, Chronic; Peritoneal Dialysis; Renal Dialysis; Risk Factors; Sorption Detoxification; Theophylline; Time Factors

Renal failure results in the retention of metabolites which may arbitrarily be grouped according to their molecular weight: low (< 300 daltons molecular weight), middle (300-15,000 daltons), and high (> 15,000 daltons). Opinion in respect to the relative importance of these groups varies. Initially it was thought that small molecules were important. In the mid-1970s, investigators identified the possible pathophysiological role of middle molecules. However, since positive identification of such molecules was difficult, opinion has shifted back in favor of small molecules, and little attention, with the exception of beta 2 microglobulin, has been paid to middle molecules and their removal by hemodialysis and related therapies. In this review current knowledge regarding middle molecules identified as uremic toxins and their removal by hemodialysis and associated therapies are discussed.

Topics: Ascorbic Acid; Atrial Natriuretic Factor; beta 2-Microglobulin; Calcitonin Gene-Related Peptide; Chloramines; Endorphins; Glycosylation; Humans; Kidney Failure, Chronic; Molecular Weight; Parathyroid Hormone; Peptides; Renal Dialysis; Toxins, Biological

Topics: Animals; Atrial Natriuretic Factor; Humans; Kidney Failure, Chronic; Sodium

Atrial natriuretic peptide (ANP) is a hormone produced, stored and secreted by atrial muscle cells. By its natriuretic, diuretic and blood pressure lowering activities ANP is possibly an endogenic antagonist for the sodium-retaining, vasopressor renin-angiotensin-aldosterone system (RAAS). In diseases associated with increased intravascular volume ANP plasma concentrations have been found elevated, in those associated with decreased volume ANP has been found decreased. In essential hypertension and chronic heart or renal failure diagnostic conclusions may be drawn from the ANP plasma concentration. This review summarizes the present knowledge about physiology and pathophysiology of ANP and values in addition the diagnostic power of ANP measurements for clinical routine in hypertension, heart and renal failure.

Topics: Atrial Natriuretic Factor; Cardiovascular Diseases; Heart Failure; Humans; Hypertension; Kidney Failure, Chronic; Plasma Volume; Renin-Angiotensin System

Topics: Atrial Natriuretic Factor; Blood Pressure; Humans; Hypertension; Hypotension; Kidney Failure, Chronic; Renal Dialysis

Topics: Atrial Natriuretic Factor; Blood Pressure; Cardiovascular Physiological Phenomena; Cardiovascular System; Humans; Kidney; Kidney Failure, Chronic; Neuropeptides; Octreotide

Topics: Atrial Natriuretic Factor; Heart Failure; Humans; Hypertension; Kidney Failure, Chronic

The discovery of atrial natriuretic peptide (ANP) has modified our current understanding of the regulation of sodium metabolism. This peptide, of which the second messenger is cyclic guanosine monophosphate (cyclic GMP), is released by the atrial myocytes in response to increased atrial stretch and has for essential function to diminish the venous return to the heart. Radioimmunoassays have demonstrated that plasma ANP and cyclic GMP levels are increased in various diseases such as congestive heart failure (CHF), renal insufficiency, and, to a lesser extent, diabetes mellitus and liver cirrhosis with ascites. Plasma ANP is of prognostic value in CHF and reflects the effective central volemia in renal failure so that its assay as well as that of plasma cyclic GMP seem of interest in these diseases. Further studies are needed to assess the pathophysiological significance of ANP in diabetes mellitus and cirrhosis, and to define the indications of the treatment by enkephalinase inhibitors which increase endogenous ANP levels by lowering the catabolism of this hormone.

Topics: Acute Kidney Injury; Animals; Atrial Natriuretic Factor; Diabetes Mellitus; Heart Atria; Humans; Kidney Failure, Chronic; Liver Cirrhosis; Rats

Topics: Acute Kidney Injury; Animals; Atrial Natriuretic Factor; Blood Volume; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Heart Atria; Homeostasis; Humans; Kidney Failure, Chronic; Kidney Glomerulus; Mitral Valve Stenosis; Natriuresis; Pulmonary Circulation; Rats; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface

Topics: Atrial Natriuretic Factor; Endocrine System Diseases; Heart Diseases; Humans; Hypertension; Kidney Failure, Chronic

Atrial natriuretic peptide is a recently discovered cardiac hormone with natriuretic, vasodilatory and hypotensive activities. The role of this hormone in the pathophysiology of hypertension is of particular interest. In contrast to an earlier concept, a deficiency of the atrial peptide could not be found in animal models of hypertension or in patients. ANP plasma levels were elevated in SHR with accelerated hypertension, in salt-sensitive Dahl rats, in rats with DOCA-salt-hypertension and in animals with renovascular hypertension. Elevated ANP levels under these conditions can be explained by an expansion of the intravascular volume or by an elevated atrial wall stretch induced by the hypertension itself. In patients with primary hypertension, plasma levels of the peptide are raised in some patients and are normal in others. Plasma ANP levels correlate with age, blood pressure and signs of left ventricular hypertrophy. A negative correlation is described between ANP and renin. Measurement of plasma ANP levels does not allow a differentiation between primary and secondary forms of hypertension. Elevated ANP levels are also found in primary hyperaldosteronism and in renal failure. Stimulation of ANP secretion by physical exercise and dietary salt loading is maintained in hypertension. Infusion of 1-28-hANP leads to a reduction in systemic arterial pressure in normotensives and hypertensives. The natriuresis induced by exogenous ANP is more pronounced in hypertensives. Stimulation of endogenous ANP secretion does not prevent the rise in blood pressure possibly due to a reduction in ANP receptors in target tissues.

Topics: Acromegaly; Animals; Atrial Natriuretic Factor; Humans; Hyperaldosteronism; Hypertension; Hypertension, Renal; Hypertension, Renovascular; Kidney Failure, Chronic; Male; Rats; Rats, Inbred Strains

Topics: Animals; Atrial Natriuretic Factor; Diuretics; Heart Failure; Humans; Kidney Failure, Chronic; Protein Conformation; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface; Renin-Angiotensin System; Tachycardia, Supraventricular

The atrial hormonal system consists of 126 amino acid-containing prohormone (proANP) stored in the secretory granules of atrial myocytes and 28 amino acid-containing hormone (ANP) that is secreted into the bloodstream in response to raised atrial pressure. ANP participates in the homeostasis of body fluid volume through its main receptor-mediated effects; natriuresis, inhibition of renin and aldosterone secretion, and vasodilation. It counteracts the renin-angiotensin system with the putative primary role of regulating the circulating blood volume. Although in man, the physiologic volume stimuli lead to relatively modest increases of ANP secretion, its plasma level undergoes striking changes in pathology. Marked elevations in conditions accompanied by fluid retention, most conspicuously in heart failure and renal failure, have been explained as a compensatory reaction to volume overload. The recent data suggest a decreased target organ responsiveness as one of the causes of a relative inefficiency of the high circulating levels of ANP in inducing an appropriate natriuresis in these volume overload conditions. The well established radioimmunoassay and the more recent methods of plasma ANP measurement are reviewed, and the authors' results with a commercial RIA are presented.

Topics: Animals; Atrial Natriuretic Factor; Cardiovascular Diseases; Humans; Kidney Failure, Chronic; Liver Cirrhosis; Radioimmunoassay; Radioligand Assay; Specimen Handling

Topics: Atrial Natriuretic Factor; Child; Humans; Kidney Failure, Chronic; Natriuresis

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Cricetinae; Dogs; Guinea Pigs; Humans; Hypertension; Kidney; Kidney Failure, Chronic; Lung Diseases, Obstructive; Natriuresis; Rats

Topics: Amino Acid Sequence; Animals; Atrial Natriuretic Factor; Blood Proteins; Cardenolides; Cattle; Digoxin; Dogs; Edema; Guinea Pigs; Humans; Hypertension; Hypothalamus; Kidney Failure, Chronic; Kidney Tubules; Muscle Proteins; Potassium; Rabbits; Saponins; Sodium; Sodium-Potassium-Exchanging ATPase

This study investigated the efficacy of human atrial natriuretic peptide (hANP, carperitide) for high-risk patients undergoing coronary artery bypass grafting (CABG).. This was a randomized controlled trial of 367 high-risk patients (European System for Cardiac Operative Risk Evaluation above 6) undergoing CABG. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE). Secondary endpoints were (1) postoperative death, (2) MACCE + hemodialysis, and (3) serum creatinine and brain natriuretic peptide (BNP) levels. Logistic regression analysis was conducted to identify preoperative and perioperative factors related to early death and MACCE.. There was no significant difference of survival between the hANP and placebo groups (p = 0.1651), but the MACCE-free rate was significantly higher in the hANP group than in the placebo group (p < 0.0001). No patient from the hANP group started hemodialysis after operation, but 7 patients did in the placebo group, and the dialysis rate was significantly lower in the hANP group (p = 0.0147). Serum creatinine and BNP were also significantly lower in the hANP group at 1 year postoperatively. MACCE were strongly associated with age 75 years or older, chronic kidney disease, hemodialysis, left ventricular dysfunction, and nonuse of carperitide.. In the early postoperative period, carperitide has a cardiorenal protective effect that prevents postoperative MACCE and hemodialysis. Perioperative low-dose carperitide infusion may be useful in high-risk patients undergoing on-pump CABG.

Topics: Aged; Atrial Natriuretic Factor; Cause of Death; Coronary Artery Bypass; Dose-Response Relationship, Drug; Female; Humans; Infusions, Intravenous; Japan; Kidney Failure, Chronic; Male; Postoperative Complications; Preoperative Care; Renal Dialysis; Risk Factors; Stroke; Survival Rate; Treatment Outcome

The purpose of this comparative study is to prove the efficacy of the human atrial natriuretic peptide (hANP) in patients with chronic kidney disease (CKD) undergoing coronary artery bypass graft surgery (CABG).. CKD is an important risk factor for cardiac surgery.. This was a randomized controlled study of 303 patients with CKD who underwent CABG, and were divided into a group who received carperitide infusion and another group without carperitide. The primary endpoints were: 1) the post-operative dialysis-free rate; and 2) serum creatinine (sCr) and estimated glomerular filtration rate. The secondary endpoints were: 1) the early post-operative outcome; 2) outcome at 1 year post-operatively; 3) the maximum sCr, the rate of increase of sCr, and an increase of sCr by ≥ 0.3 mg/dl compared with the pre-operative value; and 4) ANP and cyclic-guanosine monophosphate levels.. The post-operative sCr was significantly lower in the hANP group not only in the post-operative acute stage but also in the first year. The maximum Cr and Cr increase rate were significantly lower in the hANP group (p = 0.00665, p < 0.0001). There was no difference in mortality rate in the first year post-operatively, and fewer cardiac events and patients going on dialysis were found in the hANP group (p < 0.0001 and p = 0.0014, respectively).. In the post-operative acute stage, carperitide showed cardiorenal protective effects that prevented post-operative cardiac events and initiation of dialysis. Thus, perioperative infusion of low-dose carperitide may have a significant role in management of patients with renal dysfunction undergoing on-pump CABG. (Effectiveness of hANP for Cardiac Surgery in Patients With Moderate to Severe Preoperative Renal Dysfunction Without Dialysis [NU-HIT for CRF]; UMIN000001462).

Topics: Aged; Atrial Natriuretic Factor; Cardiovascular Diseases; Coronary Artery Bypass; Double-Blind Method; Female; Hospitals, University; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

Randomized trials have shown that icodextrin reduces the volume of extra-cellular fluid (ECFv) with variable effects on residual renal function. To explore this fluid shift and its possible mechanisms in more detail, prospectively collected data from one such trial, including measures of inflammation (C-reactive protein, tumour necrosis factor-alpha, albumin and low and high molecular weight hyaluronan) ANP (atrial naturetic peptide), an indirect marker of intra-vascular volume, plasma concentrations of icodextrin metabolites and alpha-amylase activity were analysed.. 50 patients were randomized to either 2.27% glucose or icodextrin (n = 28) for a long exchange following a month run in. Blood samples were obtained at -1, 0, 3 and 6 months, coincident with measurements of urine volume and fluid status.. In both randomized groups, a significant correlation between the fall in ECFv and the decline in urine volume was observed (P = 0.001), although the relative drop in urine volume for patients randomized to icodextrin tended to be less. At baseline, ANP was higher in patients with proportionately more ECFv for a given body water or height. Icodextrin patients had non-significantly higher ANP levels at baseline, whereas by 3 (P = 0.026) and 6 months (P = 0.016) these differed between groups due to divergence. There was a correlation between increasing ANP and reduced ECF at 3 months, r = -0.46, P = 0.007, in patients randomized to icodextrin, but not glucose. There were no relationships between fluid status and any inflammatory markers at any point of the study, with the exception of albumin at baseline, r = -0.39, P = 0.007. Amylase activities at -1 month and baseline were highly correlated, r = 0.89, P < 0.0001. Within patients, concentrations of icodextrin metabolites were highly correlated; the only predictor of between-patient variability on multivariate analysis was body weight. There was no relationship between plasma concentrations of icodextrin metabolites and any of the other clinical parameters, including change in daily ultrafiltration, urine volume, fluid or inflammatory status.. This analysis supports observational data that changes in fluid status are associated with changes in urine volume. Icodextrin was not associated with a greater fall in urine output despite its larger effect on ECFv. Changes in fluid status could not be explained or did not appear to influence systemic inflammation. Nor can they be explained by individual variability in plasma concentrations of icodextrin that are in turn inversely proportional to the volume of distribution.

Topics: Amylases; Atrial Natriuretic Factor; Body Weight; C-Reactive Protein; Extracellular Fluid; Glucans; Glucose; Hemodialysis Solutions; Humans; Hyaluronic Acid; Icodextrin; Kidney Failure, Chronic; Multivariate Analysis; Osmolar Concentration; Peritoneal Dialysis; Serum Albumin; Tumor Necrosis Factor-alpha; Ultrafiltration; Urine

Secretion of ANP (atrial natriuretic peptide) and BNP (brain natriuretic peptide) is pulsatile in healthy humans. However, the patterns of secretion of ANP and BNP have not been studied in chronic renal failure. The aim of the present study was to test the hypotheses that ANP and BNP are secreted in pulses in dialysis patients, and that pulsatile secretion is regulated by prostaglandins. Blood samples were drawn every 2 min through an intravenously inserted plastic needle over a period of 1-2 h in 13 dialysis patients and 13 healthy control subjects (Study 1), and in 15 healthy control subjects, who participated in a randomized placebo-controlled cross-over study after treatment with indomethacin and placebo (Study 2). Plasma concentrations of ANP and BNP were determined by RIAs, and the results were analysed for pulsatile behaviour by Fourier transformation. The results from Study 1 showed that the secretion of ANP and BNP was pulsatile in nine patients with chronic renal failure. The maximum amplitude was significantly higher in chronic renal failure compared with control subjects for both ANP and BNP (ANP, 4.3 compared with 0.7 pmol/l; BNP, 2.0 compared with 0.3 pmol/l; values are medians) and correlated positively with the mean plasma level of ANP (rho=0.900, P=0.001; n=9) and BNP (rho=0.983, P=0.000; n=9). The frequency was the same for patients and controls. The results from Study 2 demonstrated pulsatile secretion in all subjects, but both the amplitude and frequency were unaffected by indomethacin. The maximum amplitude correlated positively with the mean plasma level of ANP and BNP during both placebo and indomethacin treatment. It can be concluded that the secretion of ANP and BNP is pulsatile with abnormally high amplitude in chronic renal failure, that prostaglandins apparently are not involved in the secretion of these peptides in healthy subjects and that the high secretion rate in chronic renal failure results in higher ANP and BNP in plasma.

Topics: Adult; Aged; Analysis of Variance; Atrial Natriuretic Factor; Case-Control Studies; Cross-Over Studies; Cyclooxygenase Inhibitors; Female; Heart Rate; Humans; Indomethacin; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Secretory Rate

Short daily hemodialysis (HD) has a protective effect against dialysis-induced hypotension (DIH). We examined whether this effect extends beyond the treatment period.. We analyzed clinical variables in 6 patients (5 with diabetes mellitus) who underwent conventional hemodialysis (CHD) for 4 h three times weekly for 12 weeks; then short daily HD for 2 h six times weekly for 12 weeks, and then 12 more weeks of CHD. All patients had been given vasopressors for severe DIH.. The severe DIH disappeared during the short daily HD. There were significant decreases in body weight (BW), cardiothoracic ratio (CTR), blood pressure (BP), normal saline solution (NSS) amount (62.8 +/- 26.4 vs. 9.8 +/- 7.4 ml/session, p < 0.05), frequency (0.60 +/- 0.26 vs. 0.10 +/- 0.07 infusions/session, p < 0.05) and postdialysis atrial natriuretic peptide (ANP) (176.8 +/- 56.4 vs. 104.8 +/- 42.3 pg/ml, p < 0.05). Weekly ultrafiltration volume (6.3 +/- 0.9 vs. 7.9 +/- 0.7 l, p < 0.05) was significantly higher during the short daily HD period than during the first CHD period. The vasopressor treatment was therefore stopped or reduced in all patients during the short daily HD period. Because DIH recurred in the second CHD period despite a significant increase in BP, the vasopressor treatment was resumed in 5 patients. BW, CTR, NSS infusion amount and frequency, or postdialysis ANP did not differ significantly between the short daily HD and second CHD periods.. The protective effect of short daily HD against DIH lasted more than 12 weeks after the treatment ended. We therefore conclude that temporary short daily HD is useful for preventing DIH.

Topics: Aged; Anemia; Antihypertensive Agents; Appointments and Schedules; Arteriovenous Shunt, Surgical; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Diabetic Nephropathies; Echocardiography; Erythropoietin; Female; Ferritins; Humans; Hypertension, Renal; Hypotension; Iron; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Quality of Life; Recombinant Proteins; Renal Dialysis; Uremia

The concentration of heart-type fatty acid-binding protein (hFABP), a promising novel marker for detection of acute or persistent myocardial damage, is significantly influenced by renal clearance and thus has limitations to its usefulness in patients with renal dysfunction. We evaluated whether the serum ratio of hFABP to myoglobin (F/M) might be a useful marker for assessing cardiac damage in hemodialysis patients.. Serum hFABP and myoglobin were measured, and the value of F/M was calculated in 21 hemodialysis patients. Cardiac markers (cardiac troponin T [cTnT], atrial natriuretic peptide [ANP], and brain natriuretic peptide [BNP]) and echocardiographic indices (left ventricular end-diastolic dimension [LVDd], left ventricular mass index [LVMI], and inferior vena cava [IVC] dimension) were examined and compared with hFABP, myoglobin, and F/M ratios.. Serum hFABP and myoglobin levels were significantly elevated in hemodialysis patients and reduced by 30-40% during hemodialysis. The value of F/M after hemodialysis, but not the concentration of hFABP or myoglobin, had significant linear correlations with ANP, BNP, cTnT, LVDd, LVMI, and IVC.. The value of F/M after hemodialysis, but not the concentration of hFABP itself, might be a newly useful marker for estimation of cardiac damage and volume overload in hemodialysis patients.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Cardiovascular Diseases; Carrier Proteins; Echocardiography; Fatty Acid-Binding Protein 7; Fatty Acid-Binding Proteins; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Myoglobin; Natriuretic Peptide, Brain; Neoplasm Proteins; Renal Dialysis; Troponin T; Tumor Suppressor Proteins; Vena Cava, Inferior

It is hard to decide an accurate value for the so-called dry weight (DW) in hemodialysis patients with cardiac disease. Our objective is to evaluate the efficacy of echocardiography to decide DW.. 115 patients on hemodialysis were divided into 2 groups: the cardiac disease group and non-cardiac disease group. The relationship between atrial natriuretic peptide (ANP) and left ventricular end-diastolic diameter (LVDd) measured by echocardiography was examined.. There was a significant positive relationship between ANP and LVDd in the noncardiac disease group, but no significant relationship was noted in the cardiac disease group. The DW was re-evaluated and transferred into more suitable criteria for the patients who often became unconscious with decreased blood pressure during dialysis. When LVDd slightly increased beyond the new criteria of dry weight, unconsciousness was disappeared and blood pressure became stable.. Echocardiography examination is very beneficial for screening to determine DW for the patients with cardiac disease.

Topics: Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Cardiovascular Diseases; Diastole; Echocardiography; Female; Heart Ventricles; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Reproducibility of Results; Statistics as Topic; Stroke Volume; Treatment Outcome; Vena Cava, Inferior; Ventricular Function

Endothelial dysfunction is common in end-stage renal disease and may contribute to the development of both hypertension and atherosclerosis. Long-slow hemodialysis (HD) has been associated with superior blood pressure control and fewer cardiovascular complications. We hypothesized that long dialysis times would improve endothelial function compared with shorter dialysis times.. Eight long-term hemodialysis patients, not on antihypertensive drugs and with no evidence of vascular disease, were studied in a three-way randomized crossover-controlled trial. Each received, for one week and in randomized sequence, four hours of HD (SD), eight hours of HD, and eight hours of HD using a smaller dialyzer and slower blood pump. The same post-dialysis target weights were used with each treatment. On the third day of each treatment endothelium-dependent (flow mediated) and independent glyceryl trinitrate (GTN) induced vasodilation were measured by forearm strain-gauge plethysmography, and von Willebrand (vW) antigen, plasma homocysteine (tHcy) and neurohormones were measured pre- and post-dialysis.. Despite achieving target post-dialysis weights with all treatments, pre-dialysis weight tended higher on SD. Endothelial dependent vasodilation increased after all HD treatments but did not differ between them. Adrenomedullin, N-terminal brain natriuretic peptide and vW antigen increased similarly across all HD whereas atrial and C-type natriuretic peptide, and endothelin-1 decreased across dialysis and were higher with SD. Pre-dialysis plasma tHcy concentrations were 13% higher during SD treatment.. Hemodialysis improved endothelial-dependent vasodilation but the effect was similar with all three HD treatments. Improved endothelial function might result in part from altered local hormone production (endothelin-1 and adrenomedullin). These data suggest that increasing dialysis time is unlikely, in the short-term, to significantly improve endothelial function in patients with end-stage renal disease, but longer term studies are needed.

Topics: Adrenomedullin; Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Cross-Over Studies; Endothelium, Vascular; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Osmolar Concentration; Peptides; Plethysmography; Renal Dialysis; Time Factors; Vasodilation

Urodilatin (URO) is a natriuretic peptide isolated from human urine which is thought to be produced by distal tubular cells. We measured urinary URO excretion in 50 healthy children and 23 children with acute (ARF), chronic renal failure (CRF), or hereditary tubular disorders, using a specific radioimmunoassay. The mean URO excreted in these four groups was 56, 45, 94, and 121 fmol/min per 1.73 m2, respectively (differences between first three groups not significant). The variation in URO excretion was larger in patients with kidney disease than in controls. There were significant correlations between urinary URO and sodium excretion in controls and CRF, but not in ARF. URO excretion also correlated with urine flow rate in CRF. Although no correlation was found between URO excretion and creatinine clearance, urinary URO was increased in some patients with advanced CRF, which suggests stimulated tubular production to compensate for reduced sodium excretion. In view of the therapeutic potential of URO in renal insufficiency, further study of the renal handling of URO is warranted.

Topics: Acute Kidney Injury; Adolescent; Atrial Natriuretic Factor; Child; Child, Preschool; Female; Humans; Kidney Diseases; Kidney Failure, Chronic; Male; Osmolar Concentration; Peptide Fragments; Reference Values; Sodium

Radiocontrast-induced nephropathy (RCIN) is a common cause of hospital-acquired acute renal failure and is associated with a high mortality rate. RCIN is potentially preventable, because administration of the radiocontrast agent is predictable, and a high-risk population has been identified. This multicenter, prospective, randomized, double-blind, placebo-controlled trial was performed to evaluate the efficacy of intravenous atrial natriuretic peptide (anaritide, ANP 4-28) to prevent RCIN. Patients with stable chronic renal failure (serum creatinine greater than 1.8 mg/dL or serum creatinine between 1.5 and 1.8 mg/dL with estimated creatinine clearance of < or = 65 mL/min) were assigned to receive either placebo or one of three doses of anaritide (0.01 microg/kg/min, 0.05 microg/kg/min, or 0.1 microg/kg/min) for 30 minutes before and continuing for 30 minutes after radiocontrast administration. All patients were given intravenous 0.45% saline for 12 hours before the radiocontrast procedure and continuing for 12 hours after the last dose of radiocontrast. Both ionic and nonionic radiocontrast agents were administered. RCIN was defined as either an absolute increase of serum creatinine of > or = 0.5 mg/dL or a percent increase of > or = 25% over baseline. Of the 247 patients who completed the study, 50% had diabetes mellitus. There were no statistical differences in baseline serum creatinine, change in serum creatinine, or the incidence of RCIN. The incidence of RCIN was placebo, 19%; anaritide (0.01), 23%; anaritide (0.05), 23%; anaritide (0.1), 25%. Patients with diabetes mellitus had a significantly greater incidence of RCIN: placebo, 26% versus 9%; anaritide (0.01), 33% versus 13%; anaritide (0.05), 26% versus 21%; anaritide (0.1), 39% versus 8% (diabetic v nondiabetic, P < 0.002). There was no effect in the diabetic or nondiabetic groups by anaritide on the incidence of RCIN. Comparison of the highest-risk group of patients, defined as patients with diabetes mellitus and a baseline serum creatinine > or = 1.8 mg/dL, with the lowest-risk group, defined as patients without diabetes mellitus and a baseline serum creatinine of 1.8 mg/dL or less, did not show a beneficial effect of anaritide administration. In conclusion, administration of intravenous anaritide before and during a radiocontrast study did not reduce the incidence of RCIN in patients with preexisting chronic renal failure, with or without diabetes mellitus.

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Contrast Media; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Radiography; Risk Factors; Time Factors

Atrial natriuretic factor (ANF) has natriuretic, renin-suppressing and chronic hypotensive actions that may be utilized by inhibition of ANF degradation by neutral endopeptidase, E.C.24.11 (NEP). Three groups of 8 male patients [GFR 103 +/- 8 (Normal), 64 +/- 6 (Moderate CRF), and 16 +/- 2 ml/min (Severe CRF)] received 100 mg i.v. bolus of the NEP inhibitor candoxatrilat or placebo in random order in a double-blind crossover study. GFR (51CR-EDTA), ERPF (125I-hippuran). ANF (IRMA), urinary cGMP (RIA) and albumin (RIA) and sodium excretion and flow rate were measured hourly for two hours before and for seven hours after candoxatrilat administration. After candoxatrilat plasma ANF rose two- to threefold from baseline, and remained elevated for 5(N) and 7(M,S) hours (P < 0.01(N,S), P < 0.03(M)) associated with an immediate rise in urine cGMP excretion from 23.5(N), 25.4(M) and 10.4(S) nmol/hr (base) to 51.7(N), 73.8(M) and 27.5(S)(peak) lasting 7(N,M,S) hours (P < 0.01(N,M,S)). There was a marked natriuresis in all three groups, the cumulative sodium excretion at seven hours post-candoxatrilat being 104(N), 140(M), 102(S) mmol (P < 0.05(N,M,S)). This was greatest in those with moderate CRF (moderate CRF vs. normal, P = 0.036, moderate vs. severe CRF, P = 0.01, normal vs. severe CRF, P = 0.74). Following candoxatrilat there was a near doubling of the urine flow rate (P < 0.01(N,S), P < 0.02(M)). Urine albumin excretion increased in patients with renal failure (P < 0.01), but there was no change in GFR, ERPF or systemic blood pressure. We conclude that the marked natriuretic effects of acute NEP inhibition seen in normal subjects are enhanced in the presence of moderate CRF and sustained even in severe renal impairment.

Topics: Adult; Aged; Albuminuria; Atrial Natriuretic Factor; Cross-Over Studies; Cyclic GMP; Cyclohexanecarboxylic Acids; Diuresis; Double-Blind Method; Hemodynamics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Natriuresis; Neprilysin; Protease Inhibitors; Renal Circulation

We have previously reported that C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is produced in vascular endothelial cells and acts as an endothelium-derived relaxing peptide. To clarify the clinical significance of CNP in renal disorders, we examined the plasma level of CNP in patients with various cardiovascular diseases, including chronic renal failure (CRF) patients who were under hemodialysis therapy. We also investigated biological effects of intravenously-administered CNP (0.43 nmol/kg) by bolus injection from the peripheral vein in healthy volunteers and measured systemic hemodynamic variables, plasma levels of CNP, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), cGMP, aldosterone and also urine volume, urinary excretions of sodium, potassium, chloride and cGMP. The plasma CNP levels in healthy humans (N = 13) was 1.4 +/- 0.6 fmol/ml. In CRF patients, the plasma CNP significantly increased up to 3.0 +/- 1.1 fmol/ml. The administration of CNP elicited significant increase of plasma cGMP level (from 4.77 +/- 1.25 to 8.33 +/- 1.59 pmol/ml 15 min after the administration) and of urinary cGMP excretion (from 30.7 +/- 4.3 to 74.9 +/- 13.4 nmol/30 min). Intravenously-administered CNP exerted significant diuretic (% increase: +117 +/- 85.0), natriuretic, kalliuretic and chloriuretic actions with the increase of endogenous creatinine clearance. CNP also elicited significant hypotensive actions (delta BPs/delta BPd: -4.3 +/- 1.3/-4.1 +/- 1.0 mm Hg) with the concomitant increase of heart rate (+7.6 +/- 2.6 bpm). Plasma aldosterone concentration significantly decreased from 45.4 +/- 2.3 to 35.4 +/- 4.9 pg/ml 30 minutes after the administration. Taken together, these results suggest a role for CNP in human renal function.

Topics: Adult; Aged; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Diuresis; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Nerve Tissue Proteins; Proteins

In this study we investigated the interactions between volume changes (body weight), plasma atrial natriuretic peptide (pANP) and ambulatory blood pressure (BP) in 10 patients with end-stage renal disease undergoing regular hemodialysis (HD) treatment three times weekly. Most patients retained their diurnal BP variation when their BP was adequately controlled. Interdialytic weight gain was 1.3 +/- 0.2 kg and the day-time systolic BP increased 12.5 +/- 4.8 mm Hg on the second interdialytic day. pANP did not correlate (r = -0.07, p = 0.85) with this BP elevation, but there was a fairly strong positive correlation (r = 0.61, p = 0.06) between interdialytic weight gain and systolic BP. The mean pANP level decreased from 149.7 +/- 18.2 to 117 +/- 0.1 ng/l during HD and continued its decrease to 83 +/- 12.2 ng/l at 20 h after an HD session. The total decrease from 149.7 +/- 18.2 to 83 +/- 12.2 ng/l was statistically significant (p = 0.001). Since the lowest pANP value was found 20 h after completion of the dialysis session, body weight is a more reliable indicator of volume reduction during HD than pANP. The results indicate that in HD patients weight gain between two dialysis sessions increases the day-time systolic BP but not the diastolic BP. Diurnal BP variation is maintained as long as BP is adequately controlled either by volume control or by drug treatment.

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Body Weight; Circadian Rhythm; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Renal Dialysis

Two groups of subjects (uraemic and control) were studied. The group A consisted of 20 patients treated by HD (haemodialysis). The mean age was x +/- SD--36.6 +/- 7.3 years, duration of haemodialysis treatment 32.8 +/- 7.7 months, cuprophan dialyzers and acetate containing solution--35 mEq/l--were used, time of HD--4 hours 3 times weekly, predialysis serum creatinine was 876 +/- 189 mumol/l (9.8 +/- 2.1 mg%). This group of patients was subdivided in two groups. The group I comprised 9 patients with hypotensive episodes that occurred during HD (systolic blood pressure < 90 mmHg), and the group II comprised 11 patients without hypotensive episodes. The control group comprised 20 healthy subjects (mean age 36.7 +/- 12.1 years, serum creatinine level 77 +/- 16 mumol/l (0.9 +/- 0.2 mg%). In all examined subjects the following experimental protocol was used. Blood pressure (BP) was determined at about 8 a.m. after an overnight rest. Then blood samples were withdrawn for estimation of ANP, haematocrit value (Ht), haemoglobin (Hb) and creatinine concentrations. Between 8 and 12 a.m. all examined uraemic subjects were dialyzed. After each hour of dialysis BP was measured and blood samples were taken. ANP (Peninsula Lab.Kids.) was measured using RIA method, and other biochemical parameters using routine methods. Serum creatinine and plasma ANP levels significantly decreased after HD. No significant differences were seen between the both uraemic groups. No significant correlations between systolic blood pressure, ANP level in examined group were observed.. 1. In all uraemic subjects, plasma ANP level was significantly higher than in control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Creatinine; Humans; Kidney Failure, Chronic; Renal Dialysis

Two groups of subjects (uraemic and control) were studied. The uraemic group consisted of 30 patients treated by HD (haemodialysis). The mean age was x +/- SD-35.4 +/- 8.4 years, duration of haemodialysis treatment 42.8 +/- 12.1 months, cuprophan dialyzers and acetate containing solution--35 mEq/l--were used, duration of HD-4 hours 3 times weekly, predialysis serum creatinine was 1060 +/- 218 mumol/l (12.8 +/- 2.5 mg%). The control group comprised 23 healthy subjects (mean age 33.0 +/- 8.0 years, serum creatinine level 88.4 +/- 14 mumol/l (1.0 +/- 0.16 mg%). In all examined subjects the following experimental protocol was used. Blood pressure (BP) was determined at about 8 a.m. after an overnight rest. Then blood samples were withdrawn for estimation of ANP, AVP, sodium and potassium, protein, osmolality and creatinine concentrations. Between 8 and 12 a.m. all examined uraemic subjects were dialysed. After each hour of dialysis BP was measured and blood samples were taken. ANP (Peninsula Lab. Kids.) and AVP (DRG) were measured using RIA method, and other biochemical parameters using routine methods. Plasma creatinine and plasma ANP levels significantly decreased, but AVP significantly increased after HD.. 1. In all uraemic subjects, plasma ANP and AVP levels were significantly higher than in control subjects; 2. During haemodialysis with ultrafiltration a significant increase AVP level and decrease ANP level was observed; 3. A significant correlation between ANP concentration and blood pressure may suggest participation of above mentioned hormone in pathogenesis of hypertension in patients with uraemia; 4. It's possible, in pathogenesis plasma AVP increase takes part plasma ANP decrease, too.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Creatinine; Humans; Hypertension; Kidney Failure, Chronic; Middle Aged; Renal Dialysis; Vasopressins

Plasma ANF concentration in uraemic patients is very sensitive to changes in extracellular volume. It is unknown, however, if the release of this vasoactive hormone has a compensatory role in the haemodynamic response to extracellular volume expansion in these patients. We investigated the effect of isolated ultrafiltration followed by isovolumic re-expansion by saline in seven haemodialysis patients. The experiment was repeated on two occasions and the UF rate as well as the rate of volume re-expansion in the two studies were accurately matched. During the phase of volume re-expansion, we infused either ANF (0.83 microgram/min) or a placebo, in random order and cross-over. Central venous pressure, arterial pressure, haematocrit, and plasma ANF concentration were measured in baseline conditions, after ultrafiltration, and 0, 15, and 30 min after isovolumic re-expansion. In the control experiment (placebo), isolated ultrafiltration caused a marked reduction in central venous pressure and in arterial pressure and a pronounced haematocrit increase. These changes were reversed by volume re-expansion. In the active experiment, during the phase of volume re-expansion ANF infusion doubled plasma ANF concentration as compared to control experiment but it did not affect the ongoing haemodynamic response nor the haematocrit changes. Doubling of plasma ANF concentration has no influence on the haemodynamic and microcirculatory adaptations to acute volume expansion in haemodialysis patients. The data indicate that it is unlikely that raised plasma ANF concentration has a major role in the cardiovascular response to acute extracellular volume expansion in these patients.

Topics: Adult; Atrial Natriuretic Factor; Blood Volume; Body Water; Cross-Over Studies; Hemodynamics; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Renal Dialysis; Ultrafiltration

The high plasma levels of the vasodilating hormone atrial natriuretic peptide (alpha-ANP), observed in patients with chronic renal failure, decrease substantially during hemodialysis (HD), probably owing to volume reduction. Cardiovascular stability is better maintained by the use of cold dialysate although underlying mechanisms are unknown. In order to investigate the effects of different dialysate temperatures on hemodynamic stability and plasma levels of immunoreactive ANP (p-irANP), 10 stable HD patients were dialyzed with bicarbonate dialysis fluid for 240 min with each of 3 different dialysate temperatures: 36.5 degrees C (normal HD; NHD), 38.5 degrees C (warm HD; WHD) and 34.5 degrees C (cold HD; CHD). A Cuprophan plate dialyzer was used. The ultrafiltration volume and ultrafiltration rate were identical in each patient during the treatments. p-irANP was determined by radioimmunoassay, using 2 antisera which different cross-reactivity to ANP-related peptides. During NHD a nonsignificant decrease in mean arterial blood pressure from 111 +/- 5 to 103 +/- 8 mm Hg was observed. A significant (p < 0.05) decrease in mean arterial blood pressure from 109 +/- 4 to 96 +/- 6 mm Hg occurred during WHD, while during CHD it remained stable (111 +/- 4 before, 112 +/- 5 mm Hg after). Irrespective of the dialysate temperature or the antiserum used, p-irANP decreased significantly (p < 0.05) during the treatment. The reduction in p-irANP was delayed during CHD, the decrease being significantly (p < 0.05) less pronounced after 120 min. At the end of the treatment no significant difference was observed between the regimes.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Atrial Natriuretic Factor; Bicarbonates; Blood Physiological Phenomena; Blood Pressure; Body Temperature; Cold Temperature; Dialysis Solutions; Evaluation Studies as Topic; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Temperature

An elevated plasma atrial natriuretic peptide (ANP) concentration was observed in patients with chronic renal failure, and it was significantly (P < 0.01) decreased by hemodialysis with or without fluid removal. The ANP concentration was decreased by dialysis without fluid removal and the decrease was significantly (P < 0.01) correlated with the pre-dialysis value. The decrease in this peptide during fluid removal without diffusion was significantly (P < 0.05) correlated with the decrease in the circulating plasma volume measured by dye dilution. The decrease in the ANP level was therefore considered to be related to a fall in right atrial pressure caused by the decline in the circulating plasma volume. The circulating plasma volume, osmotic pressure, and blood pressure were not changed by hemodialysis without fluid removal. Moreover, the filtrate concentration of ANP (mean: 5.5 pg/ml) during fluid removal without dialysis was only about 8% of the plasma level, so filtration of ANP from the dialyzer was negligible. The decrease in ANP during hemodialysis without fluid removal may therefore have been caused by the removal of or a change in the level of substances, for example electrolytes, epinephrine, and uremic toxins. In addition to volume expansion, such a substance(s) might influence plasma ANP levels in patients with chronic renal failure.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Body Weight; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Plasma Volume; Renal Dialysis; Time Factors

Topics: Atrial Natriuretic Factor; Cyclohexanecarboxylic Acids; Double-Blind Method; Erythropoietin; Humans; Kidney Failure, Chronic; Male; Neprilysin

1. The acute effects of a single oral dose of sinorphan (100 mg), an inhibitor of neutral endopeptidase, on the plasma atrial natriuretic factor level and the fractional excretion of sodium were examined in 12 patients with severe chronic renal failure who were not on maintenance haemodialysis and who ingested a normal sodium diet. The drug was administered against placebo by a double-blind cross-over protocol. 2. Basal plasma atrial natriuretic factor level and fractional excretion of sodium were high (23.2 +/- 3.7 pmol/l and 2.64 +/- 0.38%, respectively). Sinorphan inhibited plasma neutral endopeptidase activity by 68-75% 30 min after ingestion. This effect persisted for at least 4 h. There were simultaneously increases in plasma atrial natriuretic factor and cyclic GMP levels to 1.9 and 1.4 times the basal values, respectively. Fractional excretion of sodium increased during the second and third hour periods after ingestion of the drug with a peak of 1.9 times the basal value in the second period. Changes in fractional excretion of sodium were significantly correlated with those in plasma atrial natriuretic factor and cyclic GMP levels. Plasma aldosterone level, creatinine clearance and mean blood pressure were unchanged, whereas plasma renin activity increased slightly. An increase in urinary cyclic GMP excretion was observed in parallel with the increase in plasma cyclic GMP level.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Cyclic GMP; Double-Blind Method; Female; Humans; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Neprilysin; Sodium; Sodium, Dietary; Thiorphan; Time Factors

Endocrine abnormalities in patients with chronic renal failure are well documented. The present study aimed to assess the influence of long-term erythropoietin (EPO) therapy on endocrine abnormalities in haemodialyzed patients. Two groups of haemodialyzed patients, each of which comprised 17 subjects, were examined. The first one treated by EPO (EPO group) while the second one did not receive this hormone (NO-EPO group). A complete biochemical and hormonal check-up was performed before and at the 3, 6, 9 and 12 months of the study period. Normal values for the estimated parameters were obtained in appropriately selected sex and age-matched healthy subjects. After EPO therapy an increase of the haematocrit value from 21.8 +/- 0.9% to 32.6 +/- 0.9% was observed which was accompanied by a significant decline of plasma ferritin and saturation of transferrin. In patients of the NO-EPO group a significant although less marked rise of the haematocrit value (21.4 +/- 0.4% to 24.2 +/- 0.6%) was also noticed. EPO therapy did not change electrolytes (Na, K, Ca, inorganic phosphate), osteocalcin, creatinine, glucose and alkaline phosphatase plasma levels as well as plasma concentrations of calcium related hormones (PTH, calcitonin, 1.25(OH)2D3) and vasopressin (AVP). EPO treatment induced a significant decline of somatotropin (HGH), prolactin (PRO), follitropin (FSH), lutropin (LH), ACTH, cortisol, plasma renin activity, aldosterone, insulin (IRI), glucagon (IR-G), pancreatic polypeptide (PP) and gastrin plasma levels and an increase of plasma estradiol, testosterone and atrial natriuretic peptide (ANP). These EPO induced endocrine alterations were restricted mostly to the first 6 months of EPO administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenal Cortex Hormones; Adult; Atrial Natriuretic Factor; Combined Modality Therapy; Endocrine Glands; Erythropoietin; Estradiol; Female; Hormones; Humans; Kidney Failure, Chronic; Male; Middle Aged; Pancreatic Hormones; Pituitary Hormones; Renal Dialysis; Renin

The effect of subcutaneous and intraperitoneal administration of recombinant human erythropoietin (rHuEPO) on blood pressure was evaluated in 20 patients with renal failure on continuous ambulatory peritoneal dialysis. The two groups of patients were commenced on a 16-week course of twice weekly rHuEPO by either the subcutaneous (10 patients) or the intraperitoneal route (10 patients). One patient in the latter group was subsequently excluded because of operation and transfusion. The hemoglobulin increased significantly from 6.9 +/- 0.3 g/dl to 9.8 +/- 0.6 g/dl after subcutaneous rHuEPO treatment (p less than 0.01) at an average dose of 84 +/- 9 U/kg body weight/week. For the intraperitoneal group, despite a higher average rHuEPO dosage (133 +/- 7 U/kg body weight/week), the hemoglobin level was not significantly altered (7.0 +/- 0.4 g/dl to 8.0 +/- 0.4 g/dl, p less than 0.05). During the 16-week period of rHuEPO therapy, an increase in antihypertensive therapy was required more frequently in patients in the intraperitoneal group but the difference between groups failed to reach statistical significance. There was no conclusive evidence that the rise in hematocrit was an independent precipitant of hypertension. Patients who were hypertensive prior to rHuEPO therapy appeared most susceptible to the pressor effects in that 8 of 11 treated hypertensive patients required more intensive antihypertensive treatment during EPO administration whereas none of the untreated patients developed hypertension during the study (Fisher's exact test, p = 0.007). Plasma levels of the vasoactive hormones, atrial natriuretic peptide (ANP), plasma renin activity (PRA), and endothelin (ET) remained unchanged during both subcutaneous and intraperitoneal rHuEPO therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Dose-Response Relationship, Drug; Endothelins; Erythropoietin; Female; Hemoglobins; Humans; Hypertension; Injections, Intraperitoneal; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Recombinant Proteins; Renin; Time Factors

Synthetic alpha-human atrial natriuretic peptide (hANP) was infused continuously at a rate of 80 ng/kg/min for 20 min into normal volunteers and patients with chronic renal failure (CRF) receiving hemodialysis. Blood pressure (BP) decreased significantly both in normals and in patients with CRF. The magnitude and the duration of the decrease, however, were greater in patients with CRF. The plasma aldosterone concentration (PAC) decreased significantly in normals and only minimally in patients with CRF. The half time (T1/2) of plasma hANP in patients with CRF (M +/- SE: 4.5 +/- 0.5 min) was longer than that in normals (1.8 +/- 0.2 min). Moreover, the metabolic clearance rate in patients with CRF (64 +/- 7 ml/kg/min) was less than in normals (150 +/- 20 ml/kg/min). Thus, the T1/2 in plasma of hANP in patients with CRF was noticeably longer than in a normal control group. These findings suggest that hANP suppresses PAC regardless of electrocyte imbalances and/or volume change induced by kidney dysfunction and that the kidney may be important in degrading hANP.

Topics: Adrenal Glands; Adult; Aged; Aged, 80 and over; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Half-Life; Heart Rate; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Metabolic Clearance Rate; Middle Aged; Renal Dialysis; Renin; Vasodilation

Plasma immunoreactive atrial natriuretic factor (ANF) levels, their chromatographic profiles (high-performance liquid chromatography; HPLC) and changes during sequential ultrafiltration (UF; 1 litre/h) and biochemical correction without fluid removal (BC; 3 h) were studied in 8 end-stage chronic renal failure patients on intermittent haemodialysis (greater than 1 year). Patients entered randomly the UF-BC or BC-UF protocols that were reversed after 1 week. HPLC showed a single peak of ANF immunoreactivity in plasma of end-stage chronic renal failure patients before dialysis sessions. ANF at the end of fluid removal fell by 31 +/- 2% (p less than 0.01) during UF-BC and by 30 +/- 2% (p less than 0.01) at the end of BC during BC-UF. In both sequences a further slight reduction in plasma ANF was observed during the second phase: it was 8.5 +/- 5% (n.s.) during BC of the BC-UF and 12.5 +/- 2% (p less than 0.05) during fluid removal of BC-UF. Plasma ANF was not significantly removed by the machinery. BC did not modify the microhaematocrit in the BC-UF sequence while the microhaematocrit was significantly increased by UF (13 +/- 1 and 14 +/- 1%, p less than 0.005 vs. basal, respectively), and decreased by BC in the UF-BC sequence (-5 +/- 2% vs. end UF, p less than 0.05). Serum creatinine and urea decreased significantly during BC in both protocols while they were unmodified during UF. No significant changes were seen in PRC during either protocol.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Atrial Natriuretic Factor; Blood Volume; Creatinine; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Potassium; Randomized Controlled Trials as Topic; Renal Dialysis; Ultrafiltration; Urea

This study was performed to investigate the effects of atrial natriuretic peptide (ANP) and mannitol on renal blood flow (RBF) and radiocontrast-induced nephropathy (RCIN) in human subjects with chronic renal failure. ANP preserves glomerular filtration rate or RBF (or both) in severe animal models of acute renal failure. Radiocontrast is known to substantially decrease RBF and can induce acute renal failure. Twenty consecutive patients with chronic renal failure (60% with diabetes) were randomized in a prospective, double-blind fashion to receive either ANP (50 micrograms bolus, then 1 microgram/min infusion) or mannitol (15% at 100 ml/hr) for 2 hours before and during cardiac catheterization with diatrizoate. Baseline serum creatinine level (ANP 2.4 +/- 0.7 mg/dl, mannitol 2.5 +/- 0.8 mg/dl), medications, and quantity of radiocontrast were similar in both groups. Direct measurements of RBF were made with thermodilution catheters placed in the left renal vein. RBF rose significantly (p less than 0.05), to 198% of baseline at 15 minutes and 166% of baseline at 65 minutes in the group receiving ANP and remained stable in the group receiving mannitol. ANP levels rose significantly from baseline at 5, 15, 65 and 120 minutes in both groups (p less than 0.05). Acute renal failure defined as a 0.5 mg/dl rise of creatinine within 24 hours of cardiac catheterization, developed only in patients with diabetes mellitus and was similar in both experimental groups (ANP, 50%; mannitol, 30%). Only patients with diabetes mellitus responded with an increase in RBF after a 5-minute infusion of either ANP or mannitol (diabetes, 165% +/- 28% baseline; no diabetes, 96% +/- 8% baseline) (p less than 0.05). In conclusion, RBF was maintained or increased despite administration of radiocontrast, a documented renal vasoconstrictor. Patients with diabetes mellitus had a renal vasodilatory response to drug infusion. Acute renal failure occurred to a similar extent in both groups. Plasma ANP levels rose significantly in both groups. Mannitol may induce ANP release, thus contributing to mannitol's renal effects.

Topics: Adult; Aged; Atrial Natriuretic Factor; Cardiac Catheterization; Contrast Media; Creatinine; Female; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Mannitol; Middle Aged; Renal Circulation; Risk Factors; Sodium

The diuretic and natriuretic responses to exogenous synthetic atrial natriuretic peptide (ANP) were evaluated in patients with chronic renal failure (CRF) or nephrotic syndrome (NS). Patients were studied after an oral water load (8 ml/kg in CRF and 20 ml/kg in NS patients). A short intravenous bolus of either a placebo or ANP was administered when urine output was stable. In each group of patients, three doses of ANP were injected at 24 h intervals, i.e., 1.0, 1.5, and 2.0 micrograms/kg in the CRF and 1.0, 1.5, and 3.0 micrograms/kg in the NS group. Blood pressure and heart rate were monitored throughout the study and urinary volume and electrolyte excretion were measured every 20 min up to 3 h after the bolus. An acute and transient fall in blood pressure was observed immediately after the ANP injection. It was more pronounced in CRF than in NS patients. In CRF patients, ANP caused only a slight increase in urinary volume (13.5-44% over baseline) but a significant increase in urinary sodium excretion (45-114% over baseline). In NS patients, significant increases in both urine volume (60-105%) and sodium excretion (149-248%) were also found. In these latter patients, the renal response to ANP appeared to be better preserved. The hemodynamic and renal changes induced by ANP occurred mainly during the first 20 min following the ANP administration, when the peak plasma ANP levels were obtained. However, no clear dose-response effect could be evidenced in either group with the three doses of ANP chosen in this study.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Female; Hormones; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Nephrotic Syndrome; Sodium

The aim was to study the renal and hormonal effects of intravenous 99-126 atrial natriuretic factor (ANF) infusion in a mixed group of patients who had moderate to severe chronic renal failure (CRF) and who were not treated with dialysis. The peak mean plasma level of ANF achieved during the experiment was at the upper limit of an absolute range of basal values previously recorded in a larger group of patients with similar degrees of renal impairment. A significant tissue effect was confirmed by rises in plasma and urinary cyclic guanosine monophosphate, the 'second-messenger' of ANF. ANF infusion increased sodium excretion rate by a mean of 68% compared with a fall of 40% in a placebo group, and significant increases in urinary albumin excretion occurred during the peptide infusion. Thus, the high levels of plasma ANF found in CRF may have a role in the maintenance of sodium balance. In addition, the proteinuric effect may be detrimental to long-term renal function.

Topics: Atrial Natriuretic Factor; Diuretics; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Peptide Fragments

We studied renal, hormonal and cardiovascular effects of ANF 102-126 (WY 47987) in seven patients with chronic renal failure (serum creatinine 25-68 mg/l) and in four normal volunteers. ANF or placebo bolus injections were given at 1, 2, and 3 micrograms/kg i.v. (each dose on separate days). As compared to placebo, ANF did not induce changes of renal excretory parameters, of plasma renin and aldosterone or of blood pressure and heart rate in patients. In healthy volunteers, however, the same dose of ANF increased urinary excretion of sodium, potassium, calcium, chloride and phosphorus as well as water, and creatinine clearances, and decreased plasma aldosterone. The data suggest blunted effectiveness of ANF bolus injections in patients with renal insufficiency.

Topics: Aldosterone; Atrial Natriuretic Factor; Hemodynamics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Natriuresis; Peptide Fragments; Phosphorus; Potassium; Randomized Controlled Trials as Topic; Renin

The effects and clearance of synthetic atrial natriuretic peptide (alpha-hANP) were investigated in eight patients with end-stage renal failure and six normal volunteers. ANP or vehicle was infused for 1 h at 10 pmol.kg-1.min-1 in random order on two separate occasions. During ANP infusions in end-stage renal patients, microhematocrit rose by 9.8 +/- 2% (P less than 0.005, n = 8), from base-line values of 0.24 +/- 0.02. Serum protein and albumin rose consistently. In contrast, during placebo infusions, no significant changes were seen. Blood pressure, heart rate, plasma renin concentration, serum creatinine, and electrolytes did not change significantly during either study phase. In end-stage renal failure patients, metabolic clearance rate of infused ANP was 1.04 +/- 0.095 l/min and its plasma half-life was 4 min 34 s. In normal volunteers, metabolic clearance rate was 2.6 l/min and its plasma half-life 3 min 30 s. The data suggest that ANP promotes contraction of plasma volume via a mechanism independent of renal function and also indicate that the kidney is not the only organ involved in the ANP metabolism.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Heart Rate; Humans; Kidney Failure, Chronic; Male; Metabolic Clearance Rate; Reference Values; Renin

The relationship between endogenous plasma concentrations of atrial natriuretic peptide and renin was examined in resting normal subjects and patients with cardiac impairment. To test the hypothesis that atrial natriuretic peptide inhibits renin secretion, intravenous infusions of atrial natriuretic peptide were administered to normal volunteers, patients with end-stage renal failure, and conscious dogs in both sodium-replete and sodium-depleted states. Plasma atrial natriuretic peptide and renin were inversely related in normal subjects (r = -0.52, n = 140, p less than 0.001), but a weak positive association between these two variables was observed in patients with cardiac impairment (r = 0.32, n = 60, p less than 0.02). Low doses of both 26- and 28-amino-acid human atrial natriuretic peptide (2 pmol/kg/minute for two hours) given to sodium-replete normal subjects halved plasma renin compared with time-matched placebo values (19 +/- 4 and 18 +/- 3 versus 36 +/- 8 microU/ml, p less than 0.001 for both). Incremental doses of synthetic atrial natriuretic peptide suppressed plasma renin below time-matched placebo values in both sodium-replete (maximal suppression 1.2 +/- 0.4 versus 8.6 +/- 1.4 microU/ml, p less than 0.001) and sodium-depleted (maximal suppression 18.9 +/- 4.9 versus 51 +/- 13 microU/ml, p less than 0.05) dogs. This effect was initially apparent at low doses of atrial natriuretic peptide (1 pmol/kg/minute), and renin suppression was maximal, in both states, with lesser doses of atrial natriuretic peptide than those at which maximal natriuresis was observed. Atrial natriuretic peptide administered to patients with end-stage renal failure (10 pmol/kg/minute for one hour) caused no change in plasma renin. These data confirm that atrial natriuretic peptide inhibits renin secretion in a dose-related manner and suggest that this action of the peptide is modified by both the baseline sodium status and renal function of the recipient.

Topics: Adult; Animals; Atrial Natriuretic Factor; Dogs; Heart Diseases; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renin; Sodium, Dietary

Arteriovenous fistulas (AVFs) are iatrogenic vascular connections established to allow high-flow intravascular access for patients with chronic kidney disease requiring hemodialysis. The left-right flow shunt results in changes in extracellular fluid volume and blood pressure-controlling hormones that could affect the residual kidney function. We present a case where a female patient with a brachiocephalic AVF had a fistula flow of >4 L/min. To reduce the flow, a banding procedure was performed. The patient was examined prior to banding and 1 and 2 weeks thereafter. Banding resulted in a marked decrease in AVF flow from >4 to 1 L/min and was associated with reductions in N-terminal pro-brain natriuretic peptide of 51% and 67% at 1- and 2-weeks post-banding, respectively. Mid-regional pro-atrial natriuretic peptide concentrations were reduced post-banding by 17% after 1 week and 25% after 2 weeks. After 1 week, renin, angiotensin II, and aldosterone levels in plasma decreased transiently by 44%, 47%, and >86%, respectively, and returned to pre-banding levels after 2 weeks. Creatinine clearance tended to decrease while blood pressure and total body water increased 2 weeks after banding. This indicates that high-flow AVF is associated with increased natriuretic peptides and hormones of the renin-angiotensin-aldosterone system, that may balance each other regarding fluid retention and hypertension and support remaining kidney function.

Topics: Arteriovenous Shunt, Surgical; Atrial Natriuretic Factor; Blood Flow Velocity; Female; Humans; Kidney Failure, Chronic; Middle Aged; Natriuretic Peptide, Brain; Regional Blood Flow; Renal Dialysis; Renin-Angiotensin System

Syndecan-1, a transmembrane heparan sulfate proteoglycan, associates with renal and cardiovascular functioning. We earlier reported syndecan-1 to be involved in renal tubular regeneration. We now examined plasma values of syndecan-1 in a hemodialysis cohort and its association with volume and inflammatory and endothelial markers in addition to outcome. Eighty-four prevalent hemodialysis patients were evaluated for their plasma syndecan-1 levels by ELISA before the start of hemodialysis, as well as 60, 180, and 240 min after start of dialysis. Patients were divided into sex-stratified tertiles based on predialysis plasma syndecan-1 levels. We studied the association between plasma levels of syndecan-1 and volume, inflammation, and endothelial markers and its association with cardiovascular events and all-cause mortality using Kaplan-Meier curves and Cox regression analyses with adjustments for gender, age, diabetes, and dialysis vintage. Predialysis syndecan-1 levels were twofold higher in men compared with women ( P = 0.0003). Patients in the highest predialysis plasma syndecan-1 tertile had a significantly higher ultrafiltration rate ( P = 0.034) and lower plasma values of BNP ( P = 0.019), pro-ANP ( P = 0.024), and endothelin ( P < 0.0001) compared with the two lower predialysis syndecan-1 tertiles. No significant associations with inflammatory markers were found. Cox regression analysis showed that patients in the highest syndecan-1 tertile had significantly less cardiovascular events and better survival compared with the lowest syndecan-1 tertile ( P = 0.02 and P = 0.005, respectively). In hemodialysis patients, higher plasma syndecan-1 levels were associated with lower concentrations of BNP, pro-ANP, and endothelin and with better patient survival. This may suggest that control of volume status in hemodialysis patients allows an adaptive tissue regenerative response as reflected by higher plasma syndecan-1 levels.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Endothelins; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Renal Dialysis; Risk Assessment; Risk Factors; Syndecan-1; Time Factors; Treatment Outcome; Up-Regulation; Water-Electrolyte Balance

The new polypeptide hormones adropin and irisin have a broad impact on human metabolism and energy homeostasis. They could be potential biomarkers of cardiac injury. In end-stage renal disease (ESRD), the clinical importance of adropin and irisin is yet to be investigated.. The aim of this study was to determine the relationship between these peptides and cardiac status in ESRD patients.. Seventy-nine ESRD patients on hemodialysis (HD), peritoneal dialysis (PD) or after renal transplantation (Tx), and 40 healthy, ageand sex-matched controls (CON) were included in this study. Serum concentrations of adropin and irisin were measured with enzyme-linked immunosorbent assay (ELISA). Cardiac status was estimated by transthoracic echocardiography and the plasma concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT).. The levels of irisin were significantly lower in HD patients as compared to CON. During HD sessions, the concentrations of adropin did not change significantly, whereas the concentrations of irisin increased with borderline significance. Positive correlations were evident between adropin concentration and cTnT as well as NT-proBNP. Adropin was also correlated with left ventricular systolic internal diameter (LVIDs) (r = 0.375, p = 0.045) and relative wall thickness (RWT) (r = -0.382, p = 0.034). Irisin was correlated with right ventricular diameter (RVd) (r = -0.363, p = 0.045). No correlations were found between irisin and adropin, and blood pressure (BP) measurements.. Adropin could be a new candidate marker of cardiac dysfunction in HD patients. The cause of low levels of irisin found in HD patients is still unclear. These 2 myokines should be further investigated as potential prognostic markers of cardiac status in HD patients.

Topics: Atrial Natriuretic Factor; Biomarkers; Blood Proteins; Enzyme-Linked Immunosorbent Assay; Female; Fibronectins; Humans; Intercellular Signaling Peptides and Proteins; Kidney Failure, Chronic; Myocardium; Peptide Fragments; Peptides; Protein Precursors; Renal Dialysis; White People

Left ventricular hypertrophy (LVH) is a common abnormality in hemodialysis (HD) patients. Mitochondrial dysfunction contributes to the progression of LVH. As an inner mitochondrial membrane structural protein, mitofilin plays a key role in maintaining mitochondrial structure and function. The aim of this study was to investigate the relationship between mitofilin and LVH in HD patients. A total of 98 HD patients and 32 healthy controls were included in the study. Serum N-terminal proBNP (NT-proBNP), endothelin-1 (ET-1), and atrial natriuretic peptide (ANP) were examined. The protein level of mitofilin and the mitochondrial DNA (mtDNA) copy number were estimated in peripheral blood mononuclear cells (PBMCs). The left ventricle mass index (LVMI) was evaluated in all participants, and the interaction between these variables and the LVMI was assessed. The LVMI was positively correlated with the NT-proBNP, ET-1, and ANP levels, and it was negatively correlated with mtDNA copy number and mitofilin levels. Multiple regression analysis showed that the NT-proBNP, ET-1, and ANP levels as well as mitofilin levels and mtDNA copy number were associated with the LVMI. Although further research of these associations is needed, this result suggests that LVH may affect the levels of mitofilin in HD patients.

Topics: Adult; Atrial Natriuretic Factor; Biomarkers; Cross-Sectional Studies; DNA, Mitochondrial; Echocardiography; Endothelin-1; Female; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Mitochondrial Proteins; Muscle Proteins; Natriuretic Peptide, Brain; Peptide Fragments; Renal Dialysis; Risk Factors

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Bufanolides; Female; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors; Renal Dialysis; Retrospective Studies; Time Factors; Up-Regulation

To examine possible associations between midregional proatrial natriuretic peptide (MR-proANP) and diabetic complications at baseline and risk of mortality and end-stage renal disease (ESRD) during follow-up in type 1 diabetes.. Observational study including 667 patients, with plasma MR-proANP measured at baseline. Complications were defined as micro- (n = 168) or macroalbuminuria (n = 190) (urinary albumin excretion rate (UAER) 30-299 or ≥ 300 mg/24h), previous cardiovascular disease (CVD) (n = 143), cardiac autonomic dysfunction (heart rate variability < 11 beats/min) (n = 369), and retinopathy (n = 523). Adjustments included gender, age, systolic blood pressure, estimated glomerular filtration rate (eGFR), UAER, HbA1c, total cholesterol, 24-hour urinary sodium excretion (24h-U(Na)), body mass index, daily insulin dose, antihypertensive treatment, and smoking in linear regression analyses and analysis of covariance models. Development of ESRD (dialysis, renal transplantation, or GFR/eGFR < 15 ml/min/1.73 m(2)) and mortality was recorded through national registers.. The cohort included 293 (44%) females, aged 55 ± 13 years. Plasma MR-proANP (median (interquartile)) was 74.7 (49.2-116.8) pmol/L. Adjusted, MR-proANP correlated positively with age and UAER and negatively with eGFR, 24h-U(Na), total cholesterol, and HbA1c (P < 0.05). Moreover, MR-proANP levels increased with albuminuria degree and were higher in patients with previous CVD (P ≤ 0.001), but similar in patients with or without autonomic dysfunction or retinopathy (P ≥ 0.076). During follow-up (3.5 (3.1-4.0) years), higher MR-proANP concentrations predicted ESRD and mortality combined (n = 35) adjusted for gender, age, systolic blood pressure, eGFR, and previous CVD (hazard ratio per 1SD increase in logANP: 2.8 (1.6-4.7; P < 0.001)).. Increased plasma MR-proANP was associated with impaired renal function, increased albuminuria, and previous CVD. Moreover, MR-proANP concentrations were associated with increased risk of development of ESRD and mortality combined during follow-up.

Topics: Adult; Aged; Albuminuria; Atrial Natriuretic Factor; Biomarkers; Denmark; Diabetes Complications; Diabetes Mellitus, Type 1; Female; Follow-Up Studies; Glomerular Filtration Rate; Heart Function Tests; Humans; Incidence; Kidney Failure, Chronic; Male; Middle Aged; Renal Elimination; Risk Factors; Statistics as Topic

Sympathetic over-activity is a hallmark of end stage renal disease (ESRD). Left ventricular (LV) disorders and volume overload are pervasive in ESRD and sympathetic over-activity may be a relevant mediator of the cardiovascular (CV) risk by these alterations in this population.. We investigated the relationship between a combined biomarker of LV disorders and volume excess, atrial natriuretic peptide (ANP), and the plasma concentration of nor-epinephrine (NE) in 227 ESRD patients without heart failure at baseline and modelled the risk for incident CV events by these biomarkers over a 3.5 years follow-up.. Plasma NE was strongly and independently related to ANP (β = 0.31, P < 0.001). In a multivariate Cox's regression analysis, ANP was an independent predictor of these events [HR (1-SD) 1.25, 95 % CI 1.01-1.54]. However, when NE was introduced into the multivariate model, HR by ANP reduced substantially (1.14, 95% CI 0.91-1.42) and was no longer significant (P = 0.25) while the CV risk signalled by NE was clinically relevant (HR 1.29, 95% CI 1.05-1.59) and statistically significant (P = 0.02).. In ESRD patients without heart failure, NE is strongly and independently related to ANP. The predictive power of ANP for CV events is largely captured by NE in a statistical model including both biomarkers. These data suggest that sympathetic over-activity may be a relevant mediator of the high risk of CV events triggered by LV disorders and volume excess in this population. However, further mechanistic and intervention studies are needed to prove the nature (causal/non causal) of these findings.

Topics: Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Blood Volume; Cardiovascular Diseases; Female; Follow-Up Studies; Humans; Incidence; Kidney Failure, Chronic; Male; Middle Aged; Norepinephrine; Predictive Value of Tests; Risk Factors; Sympathetic Nervous System; Ventricular Dysfunction, Left

Left ventricular hypertrophy (LVH), a common complication in chronic kidney disease (CKD), is associated with high cardiovascular mortality. The aim of this experimental study was to analyze the effect of different vitamin D receptor activators (VDRAs) on both LVH and myocardial fibrosis in chronic renal failure (CRF).. Male Wistar rats with CRF, carried out by 7/8 nephrectomy, were treated intraperitoneally with equivalent doses of VDRAs (calcitriol, paricalcitol and alfacalcidol, 5 days per week) during 4 weeks. A placebo group (CRF + vehicle) and a Sham group with normal renal function served as controls. Biochemical, morphological, functional and molecular parameters associated with LVH were evaluated, as well as cardiac fibrosis, collagen I, transforming growth factor β1 (TGFβ1) and matrix metalloproteinase-1 (MMP1) expression.. All VDRAs treatment prevented LVH, with values of cardiomyocyte size, LV wall and septum thickness and heart-body weight ratio similar to those observed in the Sham group. At molecular levels, all VDRAs attenuated atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) expression compared with CRF + vehicle. The phosphorylation of ERK1/2, a signal for activating growth, was stimulated in the CRF + vehicle group; VDRAs use prevented this activation. Paricalcitol was the only VDRA used that maintained in the normal range all parameters associated with myocardial fibrosis (total collagen, collagen I, TGFβ1 and MMP1).. Our findings demonstrated that the three VDRAs used induced similar changes in bone metabolic parameters and LVH. In addition, paricalcitol was the only VDRA which showed a relevant beneficial effect in the reduction of myocardial fibrosis, a key factor in the myocardial dysfunction in CKD patients.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Bone Density Conservation Agents; Calcitriol; Cardiomyopathies; Ergocalciferols; Fibrosis; Humans; Hydroxycholecalciferols; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; MAP Kinase Signaling System; Natriuretic Peptide, Brain; Phosphorylation; Rats; Rats, Wistar; Receptors, Calcitriol

To assess factors influencing the long-term survival of elderly dialysis patients.. The study group consisted of 51 prevalent dialysis patients aged over 70 years (32 F and 19 M, all caucasians), who had been on a chronic hemodialysis (27) or peritoneal dialysis program (24) for at least 2 months; median age was 77 years, median time on dialysis before inclusion was 16 months, and median residual diuresis was 600 ml. The patients were prospectively followed up to 4 years, and an analysis of factors affecting survival was performed.. Thirteen patients from the initial cohort of 51 (25.5 %) survived the whole 48-month observation period: 10 HD patients (37 %) and 3 PD patients (12.5 %). Annual mortality rate was 28.2 %: 37.4 % on PD vs. 20.9 % on HD. The dialysis modality had a significant impact on patients' survival (p = 0.049; Cox F-test). The independent mortality risk factors in the Cox proportional hazard regression model were higher plasma pro-atrial natriuretic peptide (pro-ANP) (p = 0.006), lower residual diuresis (p = 0.048), and lower systolic blood pressure (BP) value (p = 0.039).. Paramount for the survival of the elderly on dialysis is adequate extracellular volume control. Residual renal function is a protective factor for the survival of elderly HD patients. This observation is novel, not previously reported in an elderly dialysis population.

Topics: Aged; Atrial Natriuretic Factor; Blood Pressure; Diuresis; Female; Humans; Interleukin-1; Kidney; Kidney Failure, Chronic; Longitudinal Studies; Male; Multivariate Analysis; Peritoneal Dialysis; Proportional Hazards Models; Prospective Studies; Renal Dialysis

Low free triiodothyronine (fT3) has been associated with the presence of malnutrition-inflammation syndrome in patients with end-stage renal disease (ESRD) and decreased overall survival in ESRD. Since thyroid hormone has a particular effect on body fluid status, we hypothesized that hemodialysis patients with low-T3 syndrome might have interstitial edema. In this study, we examined the relationship between levels of thyroid hormone and body composition parameters in Japanese hemodialysis patients.. The subjects were 52 patients on maintenance hemodialysis. Serum levels of thyroid hormone and atrial natriuretic peptide (hANP) were measured. Body composition parameters were measured using a bioimpedance body composition analyzer.. Serum fT3 had positive correlations with body mass index (BMI), body fat mass (BFM), total body water (TBW) and intracellular water (ICW), and negative correlations with the ratio of extracellular water to total body water (ECW/TBW) and hANP. There were no correlations between serum fT4 and any body composition parameter. The 49 patients with data at baseline and after 1 year were divided into groups with increased (n = 33) and decreased (n = 16) fT3 after 1 year. ΔBMI and ΔBFM were significantly lower and ΔTBW, ΔICW, ΔECW and ΔECW/TBW (changes over 1 year from baseline) were significantly higher in patients with decreased fT3 compared to those with increased fT3. There was no significant difference in ΔhANP or Δcardiothoracic ratio between the two groups.. These results show that a decrease in fT3 might be associated with emaciation and interstitial edema in Japanese hemodialysis patients.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Body Composition; Body Fluids; Body Mass Index; Body Water; Edema; Emaciation; Female; Humans; Intracellular Fluid; Japan; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Retrospective Studies; Thyroxine; Triiodothyronine

Plasma concentrations of natriuretic peptides are often elevated in chronic hemodialysis patients and difficult to interpret due to accumulation, high incidence of cardiac disease and changes in volume status. Mid-regional pro-ANP is a newly developed assay whereas BNP and its fragment NT-pro-BNP are available for a longer time. In this cross-sectional study, we compared the plasma concentration of MR-pro-ANP, BNP and NT-pro-BNP in stable ambulatory hemodialysis patients (n = 239) and investigated their associations with clinical factors such as residual diuresis, cardiac status and interdialytic weight gain and with mortality.. In all patients enrolled, the plasma concentration of all natriuretic peptides were largely elevated with a median concentration of 337 pg/ml (interquartile range 146-684) for BNP, 4435 pg/ml (1687-16228) for NT-proBNP and 907 pmol/L (650-1298) for MR-pro-ANP. Plasma concentration of all natriuretic peptides correlated independently with age, degree of systolic dysfunction and negatively with residual diuresis. Dependency on residual renal clearance was strongest for the fragments MR-pro-ANP and NT-pro-BNP. The plasma concentration of all natriuretic peptides was associated with mortality within 2 years of follow-up. Receiver-operated curves revealed a low sensitivity (32-45%), but high specificity for all natriuretic peptides (85-93%) resulting in a high negative predictive (82-87%). Best cut-off values obtained from were 18 611 pg/ml for NT-pro-BNP, 958 pg/ml for BNP and 1684 pmol/L for MR-pro-ANP.. In hemodialysis patients, the fragments NTproBNP and MR-pro-ANP are largely elevated compared to BNP which is explained by accumulation. The prognostic performance of MR-pro-ANP is similar to that of NT-pro-BNP or BNP.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Cross-Sectional Studies; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Renal Dialysis; Sensitivity and Specificity; Survival Rate

Topics: Atrial Natriuretic Factor; Coronary Artery Bypass; Female; Hospitals, University; Humans; Kidney Failure, Chronic; Male

The cardiorenal syndromes (CRS) are composed of five recently defined syndromes which represent common clinical scenarios in which both the heart and the kidney are involved in a bidirectional injury process leading to dysfunction of both organs. Common to each subtype are multiple complex pathogenic factors, a precipitous decline in function and a progressive course. Most pathways that lead to CRS involve acute injury to organs which manifest evidence of chronic disease, suggesting reduced ability to sustain damage, maintain vital functions, and facilitate recovery. Prevention of CRS is an ideal clinical goal, because once initiated, CRS cannot be readily aborted, are not completely reversible, and are associated with serious consequences including hospitalization, complicated procedures, need for renal replacement therapy, and death. Principles of prevention include identification and amelioration of precipitating factors, optimal management of both chronic heart and kidney diseases, and future use of multimodality therapies for end-organ protection at the time of systemic injury. This paper will review the core concepts of prevention of CRS with practical applications to be considered in today's practice.

Topics: Anemia; Atrial Natriuretic Factor; Cardiotonic Agents; Dopamine; Heart Failure; Humans; Inflammation; Infusions, Intravenous; Kidney Diseases; Kidney Failure, Chronic; Myocardial Ischemia; Randomized Controlled Trials as Topic; Renal Circulation; Sleep Apnea, Obstructive; Sodium; Sodium Potassium Chloride Symporter Inhibitors; Syndrome

The interplay between the heart and the kidneys has received widespread attention in recent years. A novel five-class definition of cardiorenal syndromes has been proposed. The ability of two markers of cardiac dysfunction to predict progression of primary kidney disease, described by Dieplinger and his co-workers, highlights the prognostic importance of the chronic cardiorenal (types 2 and 4) syndromes.

Topics: Adrenomedullin; Age Factors; Atrial Natriuretic Factor; Biomarkers; Creatinine; Disease Progression; Glomerular Filtration Rate; Heart; Heart Failure; Humans; Kidney; Kidney Diseases; Kidney Failure, Chronic; Proteinuria; Sex Factors

Left atrial volume (LAV) has recently emerged as a useful biomarker for risk stratification and risk monitoring in patients with end stage renal disease. We investigated the relationship between cardiac natriuretic peptides (atrial natriuretic peptide [ANP] and brain natriuretic peptide [BNP]) and norepinephrine (NE) with LAV and LAV changes over time in 199 end stage renal disease patients. At baseline, LAV was directly related to BNP (r=0.60), ANP (r=0.59), and NE (r=0.28; P<0.001), and these relationships held true in multiple-regression models adjusting for potential confounders (P< or =0.003). In the longitudinal study (17+/-2 months), LAV increased from 9.8+/-4.6 to 10.9+/-5.4 mL/m(2.7) (+11%). In a multiple linear regression model, BNP (beta=0.28; P=0.003), ANP (beta=0.22; P=0.03), and NE (beta=0.27; P=0.003) predicted LAV changes. The area under the receiver operating characteristic curve for predicting LAV changes (>3 mL/m(2.7) per year) of a risk score on the basis of standard risk factors was 0.72. Plasma BNP (+12%; P=0.004), ANP (+8%; P=0.03), NE (+8%; P=0.05) and midwall fraction shortening (+8%; P=0.05) increased the area under the receiver operating characteristic curve to a significant extent, whereas LV mass did not (+5%; P=0.18). Predictive models, including BNP, ANP, and NE, maintained a satisfactory discriminatory power for LAV and LAV changes also when tested by a bootstrap resampling technique. BNP and ANP are strongly related to LAV in the end stage renal disease patients and predict LAV changes over time in these patients. Because an increased LAV underlies diastolic dysfunction and/or volume overload (ie, potentially modifiable risk factors), the measurement of the plasma concentration of these compounds might be useful for risk stratification and for guiding treatment in dialysis patients.

Topics: Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Cardiovascular Diseases; Cohort Studies; Echocardiography; Female; Heart Atria; Humans; Hypertrophy; Kidney Failure, Chronic; Longitudinal Studies; Male; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Predictive Value of Tests; Regression Analysis; Risk Factors; ROC Curve

Cardiac biomarkers have a complex interrelationship with disease pathophysiology in patients with renal dysfunction. The underlying clinical condition results in a direct effect on the normal release and clearance of cardiac troponins and natriuretic peptides. Although initial reports suggested that this might prove a major limitation in the routine clinical use of these markers, a combination of improved assay performance and a better understanding of the underlying biochemistry of these markers in health and disease has clarified the situation. Renal dysfunction does not provide a significant practical limitation to the use of cardiac biomarkers for diagnosis in acute presentation of cardiovascular disease. The direct relationship between cardiac biomarkers and renal dysfunction reflects the high incidence of cardiovascular disease and cardiac death in patients with renal dysfunction and end-stage renal disease. Elevations of the cardiac troponins are prognostic in patients with renal dysfunction and represent global diffuse myocardial injury. Elevations of natriuretic peptides also occur due to abnormalities of ventricular function. In addition, background levels will be affected by fluid and electrolyte abnormalities due to renal dysfunction. This will directly affect vascular volume and fluid distribution altering atrial and ventricular wall tension and hence rates of natriuretic peptide release and production. The challenge is for the renal physician to translate the potential for cardiovascular disease monitoring conferred by these biomarkers into improved patient management.

Topics: Atrial Natriuretic Factor; Biomarkers; Humans; Kidney Failure, Chronic; Myocytes, Cardiac; Natriuretic Peptide, Brain; Necrosis; Peptide Fragments; Troponin I; Troponin T

Plasma atrial (ANP) and brain (BNP) natriuretic peptide levels were compared to determine if transmitral flow velocity pattern is an instantaneous marker of body fluid balance in anuric patients on hemodialysis (HD). We measured plasma ANP and BNP levels and performed Doppler echocardiography in 38 anuric patients before and after HD. Patients with valvular disease, left ventricular systolic dysfunction having a fractional shortening < 0.3, arrhythmia, or left ventricular hypertrophy were excluded. The relationships between plasma ANP or BNP levels and the transmitral flow velocity pattern were evaluated. We also determined if the magnitude of the decrease in plasma ANP level was related to that in the early peak of transmitral flow velocity (peak E). The mean age of the subjects was 61.1 +/- 9.7 years. The ANP level of 213.6 +/- 146.1 pg/mL was related to peak E of 61 +/- 15 cm/s before HD (R = 0.504, P < 0.001), but not after HD. Plasma ANP level was not related to peak late transmitral flow velocity (peak A) or peak E/peak A before or after HD. BNP level was not related to the transmitral flow velocity pattern. The magnitude of decrease in hANP level during HD was significantly related to that in peak E (R = 0.342, P < 0.05). Before HD, peak E was related to the plasma ANP level, reflecting volume overload. Change in peak E showed a weak relationship with that of plasma ANP level in the same HD patient. The measurement of peak E during a HD session may potentially enable the assessment of hydration status during HD.

Topics: Aged; Atrial Natriuretic Factor; Blood Flow Velocity; Echocardiography, Doppler; Heart Rate; Heart Valve Diseases; Humans; Kidney Failure, Chronic; Middle Aged; Natriuretic Peptide, Brain; Renal Dialysis; Systole; Ventricular Dysfunction, Left

Plasma adrenomedullin (AM) reflects cardiac dysfunction and predicts survival after myocardial infarction. The present study was designed to investigate whether the mature AM (mAM) reflects status of cardiac function, systemic blood volume, or inflammation in hemodialysis patients with cardiovascular disease, and whether mortality and additional cardiovascular morbidity can be predicted by mAM.. Plasma levels of mAM, atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), norepinephrine (NE), and C-reactive protein (CRP) before hemodialysis were measured in 67 chronic hemodialysis patients with cardiovascular disease, along with 2-dimensional and Doppler echocardiographic variables.. By univariate regression analysis, mAM correlated negatively with pulmonary venous flow velocity ratio and left ventricular (LV) ejection fraction and positively with LV inflow velocity ratio, LV end-diastolic, end-systolic volume indexes, plasma CRP level, and removal fluid volume by ultrafiltration. Multivariate stepwise regression analysis revealed that mAM reflected all variables better than log [ANP], log [BNP], and log [NE]. During a 1-year follow-up period, 7 patients died and 8 had additional cardiovascular events. Event-free Kaplan-Meier curves based on the median mAM (4.55 pmol/L) showed that patients with high plasma mAM levels had higher mortality and morbidity than those with low plasma mAM levels (P = 0.0056). By Cox multivariate proportional hazard analysis, mAM was related to mortality and morbidity [hazard ratio (HR) 4.55, 95% CI 1.2-16.8, P= 0.023).. Plasma mAM reflects cardiac dysfunction, excessive blood volume, and inflammation better than ANP, BNP, and NE, resulting in a predictor of mortality and cardiovascular morbidity in hemodialysis patients with cardiovascular disease.

Topics: Adrenomedullin; Aged; Atrial Natriuretic Factor; Biomarkers; Blood Volume; C-Reactive Protein; Female; Humans; Kidney Failure, Chronic; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Peptides; Predictive Value of Tests; Renal Dialysis; Ventricular Dysfunction, Left

Hypotension and decreased serum atrial natriuretic peptide (ANP) in response to hemodialysis have both been attributed to a decrease in central blood volume. The aim of this study was to test whether circulatory performance and serum ANP were related to changes in central blood volume, in conjunction with hemodialysis with loss of plasma volume.. Ten uremic patients without cardiopulmonary symptoms were investigated before, immediately after and 2 h after a regular dialysis session. Bolus indocyanine green dilution was used for the measurements of central blood volume, cardiac output and stroke volume. Serum ANP was analyzed using a radioimmunoassay technique.. Hemodialysis resulted in a 3.8 +/- 1.3 kg decrease in weight and an increase in hemoglobin concentration, while central blood volume, stroke volume, cardiac output, blood pressure and serum ANP fell in parallel. Two h after dialysis, central blood volume recovered to its pre-dialytic level, whereas weight, plasma volume, stroke volume, blood pressure and serum ANP stayed at low levels. There were strong correlations between serum ANP and hemoglobin concentration, stroke volume, cardiac output and blood pressure, but not between serum ANP and central blood volume. Correlations between central blood volume and plasma volume, stroke volume, cardiac output, and blood pressure were also weak.. The close correlation between circulatory performance and serum ANP implies a reduction in preload in response to dialysis. The lack of correlations between central blood volume and circulatory performance and serum ANP suggests that the compliance in the central vasculature is increased in response to dialysis.

Topics: Adult; Analysis of Variance; Atrial Natriuretic Factor; Biomarkers; Blood Volume; Cardiac Output; Case-Control Studies; Female; Hemodynamics; Humans; Indocyanine Green; Kidney Failure, Chronic; Male; Middle Aged; Monitoring, Physiologic; Probability; Prospective Studies; Reference Values; Renal Dialysis; Risk Assessment; Sensitivity and Specificity

Brain natriuretic peptide (BNP) is released into circulation in response to ventricular dilatation and pressure overload. Plasma BNP concentration correlates with left ventricular mass and dysfunction, which is prevalent in hemodialysis (HD) patients.. To evaluate the potential of BNP level for determination of hydration status, we measured inferior vena caval diameter (IVCD) and BNP levels and performed bioimpedance analysis in 49 HD patients.. Pre-HD BNP levels remained unchanged after HD. Agreement between IVCD and pre-HD BNP level in overhydration was significant (kappa = 0.304). The area under the receiver operating characteristic (ROC) curve for overhydration was 0.819 for pre-HD BNP level. When extracellular fluid/total-body water (ECF/TBW) ratios of HD patients were compared with those of 723 controls, pre- and post-HD BNP levels were significantly greater in overhydrated patients. The area under the ROC curve for overhydration by ECF/TBW ratio was 0.781 for pre-HD BNP level. However, there was no significance for pre- or post-HD BNP levels on assessment of normohydration or underhydration. Pre-HD BNP level correlated significantly with post-HD BNP level, post-HD diastolic blood pressure, pulse pressure, and ECF/TBW ratio. IVCD correlated significantly with post-HD BNP level.. BNP level seems to have a limited potential for assessment of overhydration in HD patients.

Topics: Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Body Water; Cyclic GMP; Diabetic Nephropathies; Electric Impedance; Extracellular Fluid; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Renal Dialysis; ROC Curve; Sensitivity and Specificity; Ultrasonography; Vena Cava, Inferior; Ventricular Dysfunction, Left; Water Intoxication

Cardiovascular events are the major determinant of the prognosis in patients with chronic hemodialysis. The present study was designed to investigate whether increased plasma levels of atrial or brain natriuretic peptides (ANP or BNP) predict future cardiac events in such patients.. Fifty-three patients undergoing chronic hemodialysis without clinical symptoms suggestive of cardiac disorders were enrolled and their blood was sampled for ANP and BNP measurements. Electrocardiograms demonstrated left ventricular hypertrophy in 28 patients but no other abnormal findings. We followed them up for 11.3 +/- 0.2 months. The endpoint was cardiac events.. Cardiac events occurred in 13 patients (CE group). Both ANP and BNP levels were higher in CE group than in patients without cardiac events (ANP: 118 +/- 21 vs. 56 +/- 5 pg/ml, BNP: 769 +/- 204 vs. 193 +/- 25 pg/ml, respectively). Receiver operating characteristics curve revealed that the cut-off levels of ANP and BNP were 58 and 390 pg/ml, respectively. Using the Kaplan-Meier method, the incidence of cardiac events was significantly greater in patients with higher levels of ANP (50.0 vs. 0.0%) or BNP (72.7 vs. 11.9%) than in those with lower levels of the peptides.. Elevated levels of ANP or BNP indicate an increased risk of cardiac events and these peptides are clinically useful to predict cardiac events in patients with hemodialysis.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Renal Dialysis; Risk Factors; Ventricular Dysfunction, Left

Cardiac failure occasionally is caused by the creation of vascular access for hemodialysis. However, the influence of an arteriovenous (AV) fistula on cardiac function has not been fully elucidated. The present study investigated serial changes in cardiac function and hormonal levels after the AV fistula operation.. Sixteen patients with chronic renal failure underwent echocardiographic studies before and 3, 7, and 14 days after the AV fistula operation. Plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations were measured before and 1, 3, 6, 10, and 14 days after the operation.. Creation of an AV fistula produced significant elevations in left ventricular (LV) end-diastolic diameter (+4%), fractional shortening (+8%), and cardiac output (CO; +15%). In LV inflow velocities measured by Doppler echocardiography, deceleration time of the early diastolic filling wave shortened (-12%) and the ratio of the peak velocity of early diastolic to atrial filling (E-A ratio) increased (+18%). The difference in duration of LV inflow and pulmonary venous flow at atrial contraction, a marker of LV end-diastolic pressure, significantly shortened day 14 after the operation (-37%). That is, creation of an AV fistula induced LV diastolic dysfunction toward a restrictive filling pattern. Both ANP and BNP levels increased after the operation, and maximal percentages of increase were observed after 10 days (ANP, +48%; BNP, +68%). In the relationship between cardiac function and hormonal response, the increase in CO was associated with elevation of ANP levels (r = 0.61; P = 0.01), but not BNP levels. Conversely, the increase in E-A ratio correlated only with BNP level elevation (r = 0.60; P = 0.01).. Our observations indicate that creation of an AV fistula has significant effects on cardiac systolic and diastolic performance, and ANP release is induced by volume loading, but BNP release is stimulated by LV diastolic dysfunction.

Topics: Adult; Aged; Aged, 80 and over; Arteriovenous Shunt, Surgical; Atrial Natriuretic Factor; Cardiac Output; Diastole; Female; Heart Function Tests; Humans; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Renal Dialysis; Systole

Increased physical activity is followed by a stimulation of the sympathetic nervous system and this effect is probably more pronounced in patients with chronic renal failure and hypertension than in healthy controls. The role of sustained exercise in hypertensive patients with chronic renal failure, with and without antihypertensive therapy, is unclear, as is hormonal regulation of the renal hemodynamics. We hypothesized that prolonged low-intensity bicycle exercise would have a greater effect in patients with chronic renal failure than in controls, and that antihypertensive treatment would ameliorate these effects.. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), mean arterial blood pressure (MAP), norepinephrine (NE) and atrial natriuretic peptide (ANP) were measured in the upright position before and during low-intensity exercise for 2 h in healthy controls (n = 8) and in hypertensive patients with moderately reduced renal function who were not taking antihypertensives (n = 7) or who were receiving treatment with captopril (n = 10), enalapril (n = 6) or verapamil (n = 9).. GFR tended to decrease and ERPF decreased significantly in healthy individuals when exercise duration was prolonged from 1 to 2 h. An earlier decline in GFR and ERPF was seen in the renal failure patients compared with the controls. Filtration fraction (FF) increased during exercise in all groups except the group taking enalapril. MAP increased in the captopril group during exercise but was unchanged in the other groups. Treatment with captopril produced a more pronounced and earlier fall in exercise-induced GFR than in untreated controls, while verapamil treatment completely blunted the decline in GFR, with a concomitant increase in plasma ANP. No significant changes were seen in plasma NE levels, but urinary NE excretion increased in controls and captopril-treated patients during exercise.. The results suggest that prolonged low-intensity exercise has a substantially greater effect on renal hemodynamics in hypertensive renal failure patients than in healthy controls, with negligible changes in plasma NE levels. Verapamil treatment seems to ameliorate the renal effects of exercise on GFR in these patients, and this may in part be mediated via a stimulatory effect on ANP.

Topics: Adult; Antihypertensive Agents; Atrial Natriuretic Factor; Blood Pressure; Captopril; Enalapril; Exercise; Female; Glomerular Filtration Rate; Hemodynamics; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Norepinephrine; Renal Circulation; Renal Plasma Flow, Effective; Verapamil

Congestive heart failure (CHF) is a disease that is characterized by progressive left ventricular (LV) dysfunction and dilatation. Oxidative stress is thought to contribute to the progression of CHF, and antioxidants have been shown to have beneficial effects when started early after myocardial infarction (MI). In this study, we tested whether the powerful antioxidant probucol would attenuate progression of CHF once it was established after MI in the rat.. Ligation of a coronary artery was used to create an MI in rats (n=266). Survivors were then randomized 20 days after MI to either probucol 61 mg. kg(-1). d(-1) or vehicle and followed up for a total of 100 days after MI. Studies of cardiac hemodynamics, LV remodeling, cardiac apoptosis and morphology, systemic neurohumoral activation, oxidative stress, and renal function were then evaluated. Probucol improved LV function (LV maximum rate of pressure rise from 3103 to 4250 mm Hg/s, P<0.05, and LV end-diastolic pressure decrease from 28 to 24 mm Hg, P<0.05), reduced pulmonary weights, prevented right ventricular systolic hypertension, and preserved renal function compared with vehicle. Probucol also prevented LV dilatation, prevented wall thinning (1.70 versus 1.42 mm, P<0.05), reduced cardiac fibrosis and cardiac apoptosis, attenuated increased myocardial cell cross-sectional area, and increased scar thickness.. In chronic CHF, probucol exerts multiple beneficial morphological effects that result in better LV remodeling and function, reduced neurohumoral activation, and preserved renal function.

Topics: Animals; Antioxidants; Apoptosis; Atrial Natriuretic Factor; Chronic Disease; Disease Models, Animal; Heart Failure; Heart Ventricles; Hemodynamics; Kidney Failure, Chronic; Kidney Function Tests; Male; Myocardial Infarction; Myocardium; Norepinephrine; Oxidative Stress; Probucol; Rats; Rats, Wistar; Survival Rate; Time; Treatment Outcome; Ventricular Function, Left; Ventricular Remodeling

Adrenomedullin (AM), a hypotensive and natriuretic peptide, consists of an amidated mature form (mAM) and an intermediate form in human plasma, of which only mAM exerts biological activity. Like atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), plasma levels of mAM are reported to be significantly elevated in hemodialysis (HD) patients, suggesting that mAM may be stimulated partly by increased body fluid volume in a manner similar to the natriuretic peptides. Here, we examined the relationship between mAM levels and ANP or BNP levels and the effect of HD on plasma mAM in HD patients.. We measured plasma levels of mAM, total AM (tAM), ANP and BNP before and after HD in patients on long-term HD (n = 22, mean age 56.3 +/- 3.2 years) using radioimmunoassay.. Baseline mAM (2.7 +/- 0.3 fmol/ml) and tAM (23.6 +/- 2.0 fmol/ml) were significantly higher in HD patients than in healthy subjects (1.1 +/- 0.2 fmol/ml, 9.0 +/- 2.1 fmol/ml, respectively). HD significantly reduced the levels to 1.2 +/- 0.2 fmol/ml and 13.8 +/- 1.4 fmol/ml, respectively, although tAM levels were still elevated compared to healthy subjects. Similar plasma ANP and BNP levels were obtained in HD patients. There were significant correlations between mAM and tAM levels before and after HD and between HD-induced changes in mAM and tAM levels. In the pre-HD state, levels of both mAM and tAM correlated significantly with BNP levels, but the correlation of BNP with mAM was closer than that with tAM. In contrast, no correlations were observed between the 2 forms of AM and ANP. Changes in mAM levels during HD also correlated significantly with BNP but not ANP levels, although the changes in tAM did not correlate with those of the 2 natriuretic peptides.. Our results suggest that the secretion/metabolism of mAM may be regulated in a manner similar to that of BNP in HD patients.

Topics: Adrenomedullin; Adult; Atrial Natriuretic Factor; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Peptides; Radioimmunoassay; Renal Dialysis; Severity of Illness Index; Time Factors; Vasodilator Agents

Increased levels of cardiac natriuretic peptides in patients undergoing hemodialysis may be a marker of cardiomyopathy and in consequence may be suitable prognostic indicators for the risk of development of cardiac disease. We measured plasma levels of ANP, BNP, proANP(1-98) and proBNP(1-76)-related peptides with some competitive and non-competitive immunoassay methods in patients with renal failure on chronic hemodialysis in order to compare the analytical performances of these methods and to evaluate the clinical usefulness of each assay for patients with chronic renal failure. ANP and BNP values significantly decreased after hemodialysis (on average, ANP by 36% and BNP by 16%); while all proANP and proBNP values tended to increase, but only proANP(1-30) (by 14.4%) and Nt-proBNP (by 9.5%) significantly. Although significant correlations were found among all the circulating levels of cardiac peptides studied, N-terminal pro-peptides correlated better among themselves than with ANP and BNP; ANP was only slightly correlated with all the other peptides, the only exception being BNP. Only BNP levels significantly increased according to the degree of ventricular hypertrophy and/or ventricular function in patients with chronic renal failure. The ANP assay is preferable in physiological and clinical studies for the rapid changes in atrial pre-load. BNP would be more useful in the follow-up of cardiac complications in patients with end-stage renal disease on regular hemodialysis. The assays of N-terminal proANP(1-98)-and proBNP(1-76)-related peptides proved to be of limited use, because they were not able to detect acute changes in pre-load during hemodialysis and were less useful than BNP levels as markers of ventricular hypertrophy and/or functional cardiac impairment.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Binding, Competitive; Female; Humans; Immunoassay; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Protein Precursors; Renal Dialysis

In the general population, the plasma concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are useful to predict left ventricular hypertrophy (LVH) and LV systolic dysfunction. Whether these cardiac hormones have a similar diagnostic potential in dialysis patients is unknown.. We studied the diagnostic value of ANP and BNP for alterations in LV mass and function in a cohort of 246 dialysis patients without clinical evidence of heart failure.. Both ANP and BNP were independently related to left ventricular mass (P < 0.0001) as well as to ejection fraction (P < 0.0001). In an analysis based on a prospectively defined threshold (95th percentile of the normal range), BNP had a significantly higher (P < 0.01) sensitivity (88%) than ANP (51%) for the diagnosis of LVH, but the positive predictive value of the two peptides was very similar (92 and 87%, respectively, P = NS). However, the negative predictive value of BNP for excluding LVH was 22% higher than that of ANP (53 vs. 31%, P = 0.05). Both natriuretic peptides had a high sensitivity for the detection of LV dysfunction (87 and 94%), but their positive predictive value was low (25 and 15%). Importantly, both ANP and BNP proved to be very useful for excluding this alteration (negative predictive value 97 and 96%, respectively). An analysis based on the "best cut-offs" of each peptide as identified on the basis of the ROC curves augmented the positive and negative prediction values of BNP for the diagnosis of LVH to 95 and 61%, respectively. This approach also raised the BNP-positive prediction value for the identification of LV dysfunction to 31% but did not modify the diagnostic potential of ANP (either for LVH or for LV dysfunction).. Measuring the plasma concentration of cardiac natriuretic hormones, particularly BNP, may be useful for the identification of dialysis patients with LVH or for excluding systolic dysfunction.

Topics: Aged; Atrial Natriuretic Factor; Cohort Studies; Female; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Peritoneal Dialysis, Continuous Ambulatory; Prognosis; Renal Dialysis; ROC Curve; Ventricular Dysfunction, Left

The N-terminal proatrial natriuretic peptide (proANP) has become an important parameter for assessing the prognosis of patients with cardiac disease. Its use for evaluating the hydration status in patients with chronic renal failure, however, is still under investigation. The present study comprised 12 haemodialysis (HD) and 17 pre-dialysis patients. In the HD patients, the inferior vena cava diameter during quiet expiration (IVCe) was estimated by ultrasonography and plasma concentrations of N-terminal proANP, atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (cGMP) were measured before and 4 h after termination of HD. In the pre-dialysis patients venous blood samples were taken during rest to measure plasma N-terminal proANP and ANP and serum creatinine. Normal values for N-terminal proANP and ANP were obtained from 18 healthy volunteers. The plasma concentrations of N-terminal proANP and ANP in healthy volunteers were 328 +/- 92 and 11.4.0 +/- 3.1 pM L-1, respectively. In pre-dialysis patients, serum creatinine ranged from 110 to 447 microM L-1 and was significantly correlated to plasma N-terminal proANP (r = 0.60, P < 0.05) but not to ANP. This may indicate that N-terminal proANP is more dependent on renal function for its clearance than ANP, which is probably cleared by extrarenal mechanisms as well. In HD patients, IVCe was significantly correlated to the three hormones before HD, most strongly to N-terminal proANP. After dialysis, IVCe was significantly correlated to ANP and cGMP but was not correlated to N-terminal proANP. This may suggest that proANP takes a longer time than other hormones to reflect changes in intravascular volume. In conclusion, N-terminal proANP is a hormone closely related to degree of renal function. Furthermore, it is a sensitive marker reflecting the interdialytic hydration status in HD patients, as indicated by its high correlation to IVCe, a standard method which is used frequently nowadays to assess the body hydration. However N-terminal proANP could not reflect the acute changes in fluid volume induced by HD, probably because it is slowly metabolized.

Topics: Adult; Aged; Atrial Natriuretic Factor; Creatinine; Cyclic GMP; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prognosis; Protein Precursors; Reference Values; Renal Dialysis; Ultrasonography; Vena Cava, Inferior; Water-Electrolyte Balance

A noninvasive biochemical testing method for early detection and monitoring the condition of cardiac complications in hemodialysis (HD) patients would be useful and might lead to improved survival. The aim of this study is to clarify the pathophysiological significance of plasma brain natriuretic peptide (BNP) levels in HD patients with and without coronary artery disease (CAD). We measured plasma atrial natriuretic peptide (ANP) and BNP levels on Monday, Wednesday, and Friday before and after HD in 28 consecutive patients who underwent HD three times weekly. In addition, we measured plasma ANP and BNP levels in 21 HD patients with CAD and 27 HD patients without CAD and studied the relationships between BNP levels and cardiac function and clinical variables. Plasma ANP levels significantly decreased after HD on Monday, Wednesday, and Friday, and predialysis plasma ANP levels on Monday were significantly greater than those on other days. Plasma BNP levels did not change after HD on Monday; however, they significantly decreased after HD on Wednesday and FRIDAY: Predialysis plasma BNP levels on Monday were greater than those on other days, and postdialysis plasma BNP levels on Monday were greater than predialysis plasma BNP levels on WEDNESDAY: Plasma BNP levels in HD patients with CAD were significantly greater than those in HD patients without CAD and significantly correlated with left ventricular (LV) ejection fraction (r = -0.69), end-diastolic volume index (r = 0.59), and end-systolic volume index (r = 0.84) determined by left ventriculography. Conversely, plasma BNP levels in HD patients without CAD significantly correlated with LV mass index (r = 0.54) determined by echocardiography and mean systolic blood pressure (r = 0.72) determined by 48-hour ambulatory blood pressure monitoring. These results suggest the following: (1) plasma BNP levels before and after HD in chronic HD patients directly correlate with the degree of body fluid retention, and the day of the week on which the sample is obtained should be considered for its evaluation; (2) plasma BNP levels reflect LV function in HD patients with CAD; and (3) plasma BNP levels reflect LV mass and blood pressure in HD patients without CAD.

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Coronary Disease; Female; Heart Ventricles; Humans; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Renal Dialysis

This study was designed to investigate the relationship among brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) and left ventricular mass (LVM), ejection fraction, and LV geometry in a large cohort of dialysis patients without heart failure (n = 246) and to test the prediction power of these peptides for total and cardiovascular mortality. In separate multivariate models of LVM, BNP and ANP were the strongest independent correlates of the LVM index. In these models, the predictive power of BNP was slightly stronger than that of ANP. Both natriuretic peptides also were the strongest independent predictors of ejection fraction, and again BNP was a slightly better predictor of ejection fraction than ANP. In separate multivariate Cox models, the relative risk of death was significantly higher in patients of the third tertile of the distribution of BNP and ANP than in those of the first tertile (BNP, 7.14 [95% confidence interval (CI), 2.83 to 18.01, P = 0.00001]; ANP, 4.22 [95% CI, 1.79 to 9.92, P = 0.001]), and a similar difference was found for cardiovascular death (BNP, 6.72 [95% CI, 2.44 to 18.54, P = 0.0002]; ANP, 3.80 [95% CI, 1.44 to 10.03, P = 0.007]). BNP but not ANP remained as an independent predictor of death in a Cox's model including LVM and ejection fraction. Cardiac natriuretic peptides are linked independently to LVM and function in dialysis patients and predict overall and cardiovascular mortality. The measurement of the plasma concentration of BNP and ANP may be useful for risk stratification in these patients.

Topics: Aged; Atrial Natriuretic Factor; Brain-Derived Neurotrophic Factor; Cohort Studies; Echocardiography; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Multivariate Analysis; Myocardium; Natriuretic Agents; Peritoneal Dialysis, Continuous Ambulatory; Prognosis; Proportional Hazards Models; Renal Dialysis; Renal Replacement Therapy; Stroke Volume; Ventricular Function, Left

Atrial natriuretic peptide (ANP) is a hormone with well-known diuretic and vasodilating properties. Recently it was reported that ANP could increase the peritoneal fluid formation and increase peritoneal solute clearance. This study investigated the effect of ANP on peritoneal fluid and solute transport characteristics.. Eighteen male Sprague-Dawley rats were divided into three groups. A four-hour dwell study using 25 mL 2.27% glucose dialysis solution with 50 microg/kg ANP (N = 6, H-ANP) or 5 microg/kg ANP (N = 6, L-ANP) or without ANP (N = 8, control) and frequent dialysate and blood sampling was done in each rat. Radiolabeled human albumin (RISA) was added to the solution as an intraperitoneal volume marker.. The intraperitoneal volume was significantly higher in the H-ANP group as compared with the control group and the L-ANP group. The drainage volume was 26.2 +/- 1.1, 25.5 +/- 0.7, and 29.8 +/- 0.8 mL for the control, L-ANP, and H-ANP groups, respectively (P < 0.01). This was related to significant differences in the peritoneal fluid absorption rates (K(E); estimated as the RISA elimination coefficient): 39 +/- 3, 38 +/- 3, and 19 +/- 4 microL/min, and in the direct lymphatic absorption rate (K(EB); estimated as the clearance of RISA from dialysate to blood): 7 +/- 1, 6 +/- 1, and 4 +/- 1 microL/min for the control, L-ANP, and H-ANP groups, respectively (all P < 0.01). No differences were found in the intraperitoneal volume, K(E), and K(EB) between the control group and the L-ANP group. The diffusive mass transport coefficient (K(BD)) for urea, sodium, potassium, and total protein did not differ among the three groups. However, the glucose D/D(0) was significantly higher, and the K(BD) for glucose was significantly lower in the H-ANP group as compared with the other two groups. Solute clearances (+175% for sodium and +26% for potassium) were significantly increased in the H-ANP group, mainly as a result of the increased fluid removal in this group.. Our results suggest that ANP may decrease peritoneal fluid absorption (by 51%, partially because of decreasing the direct lymphatic absorption), resulting in a significant increase in peritoneal fluid removal and small solute clearances. While the basic diffusive permeability of the peritoneal membrane was not changed, the peritoneal glucose absorption was retarded by adding ANP to peritoneal dialysate, perhaps through interaction of ANP with glucose metabolism.

Topics: Analysis of Variance; Animals; Ascitic Fluid; Atrial Natriuretic Factor; Blood Proteins; Dialysis Solutions; Glucose; Kidney Failure, Chronic; Male; Peritoneal Dialysis, Continuous Ambulatory; Peritoneum; Potassium; Rats; Rats, Sprague-Dawley; Sodium; Urea; Water-Electrolyte Balance

It has been suggested that analyzing the left ventricular long axis motion can result in the sensitive detection of cardiac functional disorders.. To evaluate the usefulness of left ventricular long axis indices in managing patients on maintenance hemodialysis.. Eighteen hemodialysis patients (mean age 51 +/- 10 years) as well as 16 healthy persons (mean age 49 +/- 9 years) were examined. Echocardiograms were recorded, and the plasma concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were measured before and after a session of hemodialysis. The following parameters were measured: the left atrial diameter (LAD) and end-diastolic left ventricular diameter (LVDd) from M-mode echocardiograms, the end-diastolic LV volume (LVEDV) and ejection fraction (EF) from 2-D echocardiography, the E/A ratio from transmitral Doppler, the atrial systolic excursion of long axis motion of the mitral ring (ALAM) and maximal lengthening rate of the mitral ring toward the left atrium during the early diastolic phase (MLRe) from LV long axis M-mode echocardiograms.. LAD, LVDd, LVEDV, and ALAM showed a positive correlation with plasma levels of ANP and BNP. EF, the E/A ratio, and MLRe showed a negative correlation with plasma levels of ANP and BNP. Changes in ALAM and plasma levels of ANP during hemodialysis were larger in the subgroup of ALAM < or = 0.55 cm before hemodialysis than in the subgroup of ALAM < 0.55 cm before hemodialysis.. These results indicate that the left ventricular long axis index can detect a disorder of left ventricular diastolic function, and that a hemodialysis patient whose ALAM before hemodialysis is < 0.55 cm is dialyzed with good volume control conditions.

Topics: Adult; Aged; Atrial Natriuretic Factor; Echocardiography; Female; Heart Ventricles; Hemodynamics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Renal Dialysis; Ventricular Function

Adrenomedullin (AM) is a hypotensive peptide that has recently been isolated from human pheochromocytoma. In this study, we measured plasma AM concentrations in 54 patients on hemodialysis (HD) and examined the clinical significance. We also evaluated the effects of high-flux and low-flux dialysis membranes on plasma AM levels. The average value of plasma AM at pre-HD (4.44 +/- 0.16 fmol/ml) was significantly elevated compared with that in 44 healthy volunteers (1.31 +/- 1.41 fmol/ml) (p < 0.0001). The plasma AM concentrations at pre-HD showed a negative correlation with age and mean blood pressure (MBP) at pre-HD. The plasma AM concentrations at post-HD showed a negative correlation with MBP at post-HD and a negative correlation with the reduction rate of AM. Multiple regression analysis showed that age and MBP were independent factors associated with plasma AM at pre-HD and that MBP and reduction rate of AM were independent factors associated with plasma AM at post-HD. We investigated the differences between high-flux dialyzers (PS-UW, PS-N and FB-F) and a low-flux dialyzer (AM-BC-F), and we found that high-flux dialyzers removed plasma AM more efficiently than a low-flux dialyzer did. In addition, in 3 patients on HD, plasma AM levels decreased significantly during isovolumic dialysis using a high-flux dialyzer, despite the fact that there were no significant changes in MBP and ANP. In conclusion, elevation in plasma AM level causes a fall in MBP in patients on HD, therefore, removal of AM by HD treatment using a high-flux dialyzer contributes to the stability of blood pressure during HD.

Topics: Adrenomedullin; Atrial Natriuretic Factor; Blood Pressure; Female; Humans; Kidney Failure, Chronic; Male; Membranes, Artificial; Middle Aged; Peptides; Regression Analysis; Renal Dialysis

It has been recently suggested that cardiac troponin T (cTnT) may be more sensitive than troponin I (cTnI) for subclinical myocardial cell injury in patients on chronic dialysis.. We prospectively compared the predictive value of cTnT with cTnI, atrial (ANP) and brain natriuretic peptide (BNP) in 100 consecutive outpatients on chronic dialysis without acute coronary syndromes over a period of 3 months, and assessed whether the combination of cTnT with clinical information including age, duration of dialysis, and medical histories was useful for risk stratification of these patients. During the 2-year follow-up period, 19 patients died, mostly due to cardiac causes (53%).. The area under the receiver operator characteristic (ROC) curve for the cTnT as predictor of both overall and cardiac death was significantly greater than the area under the cTnI curve (p < 0.0001 and p = 0.01), the BNP curve (p < 0.001 and p < 0.01) or the ANP curve (p < 0.0001 and p < 0.005). In a stepwise multivariate Cox regression analysis, only cTnT (p < 0.05 and p < 0.01) and a history of heart failure requiring hospitalization (p < 0.05 and p < 0.005) were independent predictors of both all cause and cardiac mortality. Using parameters of cTnT > or =0.1 microg/l and/or history of heart failure, the overall and cardiac mortality rate for the low risk group (n=66) were 4.5% and 1.5%, respectively, 40% and 16% for the intermediate risk group (n=25), and 67% and 56% for the high risk group (n=9).. cTnT concentrations offer a higher prognostic accuracy than cTnI, ANP and BNP in patients on chronic dialysis. The combination of elevated cTnT and a history of heart failure may be a highly effective means of risk stratification of these patients.

Topics: Adult; Aged; Atrial Natriuretic Factor; Cardiovascular Diseases; Female; Heart Failure; Humans; Kidney Failure, Chronic; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Predictive Value of Tests; Prospective Studies; Renal Dialysis; Risk Factors; ROC Curve; Survival Rate; Troponin I; Troponin T

Although left ventricular hypertrophy (LVH) is a common complication which contributes substantially to high cardiovascular mortality and morbidity in end-stage renal failure, whether changes in blood pressure and alterations of circadian variation of blood pressure occur between the hemodialysis (HD) day and the interdialytic day, and if so, whether they influence the left ventricular mass (LVM) remain unknown. Thirty-five consecutive stable patients who had had a hematocrit value greater than 25% for the previous 6 months, who had been on the same antihypertensive drugs during this period, and who underwent HD 3 times a week were included. Echocardiograms were recorded after HD and then ambulatory blood pressure monitoring was recorded every hour for 48 h. The mean interdialytic body weight gain was less than 5% of dry weight. Patients with LVH had a higher average systolic blood pressure (SBP) at predialysis, postdialysis, on the HD day and on the interdialytic day than those without LVH despite the higher antihypertensive therapy rate. The majority of patients with LVH showed concentric hypertrophy and higher plasma natriuretic peptide levels. Irrespective of the presence of LVH, the average blood pressure value did not change between the HD day and the interdialytic day, and a loss of circadian blood pressure variation was observed on both the HD and interdialytic days. Univariate analysis revealed that LVM was significantly correlated with the average SBP at predialysis, postdialysis, on the HD day, on the interdialytic day and over 48 h (r= 0.48, r=0.61, r=0.67, r=0.67, r=0.73, respectively; all p<0.05). Multiple regression analysis revealed that 48-h SBP was independently associated with the LVM index. These results suggest that neither the loss of circadian blood pressure variation nor the changes of blood pressure between the HD and interdialytic days was of major etiologic importance in the development of LVH, and that the absolute value of the 48-hour average SBP may be an important risk factor for concentric LVH in stable HD patients.

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Circadian Rhythm; Echocardiography; Female; Humans; Hypertension, Renal; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Regression Analysis; Renal Dialysis

To determine levels of natriuretic peptides (NPs) in patients with end-stage renal disease (ESRD) and to examine the relationship of these cardiovascular peptides to left ventricular hypertrophy (LVH) and to cardiac mortality.. One hundred twelve dialysis patients without clinical evidence of congestive heart failure underwent plasma measurement of NP concentrations and echocardiographic investigation for left ventricular mass index (LVMI).. Plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations correlated positively with LVMI and inversely with left ventricular ejection fraction, whereas C-type NP and Dendroaspis NP levels did not correlate with LVMI. In dialysis patients with LVH (LVMI >125 g/m2), plasma ANP and BNP concentrations were increased compared with those in dialysis patients without LVH (both P<001). In a subset of 15 dialysis patients without LVH or other concomitant diseases, plasma BNP concentrations were not significantly increased compared with those in 35 controls (mean +/- SD, 20.1+/-13.4 vs 13.5+/-9.6 pg/mL; P=.06), demonstrating that the BNP concentration was not increased by renal dysfunction alone. Furthermore, the BNP level was significantly higher in the 16 patients who died from cardiovascular causes compared with survivors (mean +/- SD, 129+/-13 vs 57+/-7 pg/mL; P<.003) and was significantly associated with greater risk of cardiovascular death in Cox regression analysis (P<.001), as was the ANP level (P=.002).. Elevation of the plasma BNP concentration is more specifically related to LVH compared with the other NP levels in patients with ESRD independent of congestive heart failure. Thus, BNP serves as an important plasma biomarker for ventricular hypertrophy in dialysis patients with ESRD.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Case-Control Studies; Comorbidity; Female; Hemodynamics; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Renal Dialysis; Risk Factors; ROC Curve

The renal functional consequences of an activated sympathetic nervous system and plasma atrial natriuretic hormone (ANP) in various renal diseases are not well described. We hypothesize that norepinephrine (NE) and ANP have antagonizing effects on renal hemodynamics in diseased kidneys.. Plasma NE, ANP. glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and mean arterial pressure (MAP) were measured in the upright position in healthy controls (n = 9) and hypertensive patients with reduced GFR (n =11). The same parameters were compared between healthy controls (n = 6) and hypertensive patients with reduced GFR (n = 6) in upright and supine positions.. Upright plasma NE and ANP were significantly elevated in the patients compared with the controls (4.4 +/- 0.4 vs 2.1 +/- 0.2 nmol/l (p < 0.001) and 1.3.5 +/- 2.1 vs 6.9 +/- 1.0 nmol/l (p < 0.01) respectively). With change from upright to supine position plasma NE decreased in the controls (2.2 +/- 0.3 vs 1.7 +/- 0.3 nmol/l) (p < 0.01) and patients (3.8 +/- 0.4 vs 2.6 +/- 0.4) (p < 0.01). Supine ANP increased in controls (5.5 +/- 1.0 vs 8.3 +/- 1.1) (p < 0.01) but not in patients (14.3 +/- 3.8 vs 16.1 +/- 3.8 nmol/l) (p > 0.10). Plasma NE correlated positively with MAP (p < 0.001) and negatively with GFR (p < 0.01) in the upright but not supine position. A positive correlation between NE and ANP was observed in upright (p < 0.001) but not in supine position. ANP correlated negatively with GFR in the upright (p < 0.01) but not supine position. No position dependent changes were seen in GFR and ERPF, but supine filtration fraction (FF) increased insignificantly in the patient group (0.23 +/- 0.02 vs 0.24 +/- 0.02) (p < 0.05).. Hypertensive patients with reduced GFR have elevated levels of plasma NE and ANP in the upright body position. When the upright and supine positions are compared, plasma NE declines in the supine position in controls and hypertensive renal failure patients. and plasma ANP levels are elevated only in the upright position in hypertensive renal failure patients where the sympathetic nervous system is activated. A significant positive relationship between plasma NE and ANP was observed only in the upright position. The upright body position seems superior to recumbency in the characterization of these hormonal changes in hypertensive chronic renal failure patients.

Topics: Atrial Natriuretic Factor; Blood Pressure; Female; Glomerular Filtration Rate; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Norepinephrine; Posture; Renal Plasma Flow, Effective; Sympathetic Nervous System; Sympathomimetics

Uroguanylin, originally isolated from urine, is a new natriuretic peptide. Its plasma level is increased in association with renal impairment and fluid retention in patients with renal diseases.. Uroguanylin concentrations were measured in patients on hemodialysis (HD, n = 76) and those on continuous ambulatory peritoneal dialysis (CAPD, n = 10) using a sensitive ra- dioimmunoassay for human uroguanylin.. Plasma concentrations of immunoreactive (ir)-uroguanylin in the patients on HD and CAPD (212.0 +/- 17.4 and 245.3 +/- 39.5 fmol/ml) were significantly higher than the value for the normal controls (5.0 +/- 0.3 fmol/ml). Plasma ir-uroguanylin levels before the start of regular HD were correlated with predialysis excess weight based on their dry weights (r = 0.33, p < 0.01) and with dialysis duration (r = 0.26, p < 0.05). The plasma levels in patients with HD, for whom high-flux membranes were used, were decreased at the end of regular HD as compared with the prior levels (p < 0.05), but not in those who underwent HD with conventional membranes.. These findings suggest that the plasma ir-uroguanylin level is related to the patient's volume status as well as renal impairment. Whether the accumulation of uroguanylin has a pathological effect has yet to be determined.

Topics: Adult; Atrial Natriuretic Factor; Body Weight; Female; Humans; Immunoassay; Kidney Failure, Chronic; Male; Membranes, Artificial; Middle Aged; Natriuretic Peptides; Peptides; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis

Fragments derived from the prohormone of alpha-human atrial natriuretic peptide (alpha-ANP) in patients with cardiac failure are more closely related to the disease state than intact alpha-ANP.. Specific immunoassays have been developed to detect proANP 1-30, proANP 31-67, and proANP 1-98. Plasma concentrations of these fragments were determined in 122 hemodialysis patients with and without cardiac dysfunction, with and without hypertension, as well as with and without dialysis-associated hypotensive episodes either before or after a regularly scheduled hemodialysis session. The effects of different dialyzer membranes were also evaluated. The results of these assays along with other markers of volume regulation such as alpha-ANP and cyclic 3',5' guanosine monophosphate (cGMP) were compared with those of healthy controls.. Predialytic and postdialytic plasma concentrations of the proANP fragments were markedly higher in uremic patients than in controls (98-fold for proANP 1-98, 56-fold for proANP 31-67, and 35-fold for proANP 1-30). All proANP fragments, alpha-ANP, and cGMP decreased during hemodialysis. A strong linear correlation was found between predialytic and postdialytic plasma levels. There was no correlation, however, with the amount of fluid removed during hemodialysis. Patients with altered left ventricular hemodynamics displayed significantly higher plasma concentrations of all proANP fragments and alpha-ANP, but not cGMP, than patients with normal cardiac function. Hemodialysis patients with moderate or severe hypertension had higher concentrations of proANP fragments, alpha-ANP, and cGMP than patients with normal blood pressure or patients with only mild hypertension. There was no significant difference in circulating levels of proANP peptides, alpha-ANP, and cGMP between patients with and without frequent dialysis-associated hypotensive episodes. Cellulose-triacetate dialyzers reduced plasma levels of proANP 1-30, proANP 31-67, and proANP 1-98 significantly more than polysulfone dialyzers, but alpha-ANP and cGMP levels were not different.. Circulating alpha-ANP and proANP fragments are influenced by a variety of factors such as end-stage renal disease, hemodialysis treatment, dialyzer membrane material, cardiac dysfunction, and hypertension. Therefore, these are not useful markers to accurately estimate volume status in hemodialysis patients.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Blood Pressure; Blood Volume; Cyclic GMP; Female; Heart Failure; Humans; Hypertension, Renal; Kidney Failure, Chronic; Male; Membranes, Artificial; Middle Aged; Peptide Fragments; Protein Precursors; Renal Dialysis

Nitric oxide exerts multiple effects on renal function. It remains unclear whether endogenous nitric oxide production is increased or decreased in patients with chronic renal failure. To evaluate endogenous nitric oxide production in these patients we studied exhaled nitric oxide output by an ozone chemiluminescence method and plasma NO2(-)/NO3(-) levels by the Griess method in 40 patients with end-stage chronic renal failure who underwent regular continuous ambulatory peritoneal dialysis (n=30) or haemodialysis (n=10), and in 28 healthy subjects. Patients with chronic renal failure had a higher exhaled nitric oxide concentration [39+/-3 versus 19+/-1 parts per billion, (mean+/-S.E.M.), P<0.0001], a greater nitric oxide output (177+/-11 versus 96+/-7 nl.min-1.m-2, P<0.001) and a higher plasma NO2(-)/NO3(-) concentration (96+/-14 versus 33+/-4 micromol, P<0.01) than controls. These values did not differ between patients on haemodialysis and those on continuous ambulatory peritoneal dialysis. Patients with chronic renal failure had significantly higher plasma concentrations of both interleukin-1beta and interferon-gamma than controls. The exhaled nitric oxide output did not correlate with plasma NO2(-)/NO3(-) or with peritoneal dialysate NO2(-)/NO3(-), but plasma NO2(-)/NO3(-) correlated with dialysate NO2(-)/NO3(-) in patients who underwent continuous ambulatory peritoneal dialysis (r=0.77, P<0.01). Haemodialysis for 4 h acutely decreased plasma NO2(-)/NO3(-) (92+/-17 versus 50+/-8 micromol, P<0.05) and cGMP concentration (16.5+/-4.3 versus 5.1+/-1. 7 pmol/ml, P<0.01), but did not decrease exhaled nitric oxide output. The increase in exhaled nitric oxide with the simultaneous increase in circulating cytokines suggests that nitric oxide synthase seems to be induced significantly in patients with chronic renal failure. Increased endogenous nitric oxide production may have a pathophysiological role in patients with uraemia.

Topics: Analysis of Variance; Atrial Natriuretic Factor; Breath Tests; Chi-Square Distribution; Cyclic GMP; Female; Humans; Interferon-gamma; Interleukin-1; Kidney Failure, Chronic; Luminescent Measurements; Male; Middle Aged; Natriuretic Peptide, Brain; Nitrates; Nitric Oxide; Nitrites; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis; Time Factors

The effect of volume reduction on vasoactive substances and their role in estimating dry weight in haemodialysis patients was studied. Plasma atrial natriuretic peptide (ANP), catecholamines, antidiuretic hormone, renin activity and serum aldosterone were measured in 12 patients before and after bicarbonate haemodialysis. Haemodynamical changes were registered and cardiac function and diameter of the inferior vena cava were measured by echocardiography before and after dialysis. Plasma concentration of ANP was significantly reduced by haemodialysis from 209 +/- 51 to 69 +/- 13 pg mL(-1) (n = 12, P < 0.05), whereas concentrations of the other hormones were unchanged. The change in the concentration of ANP did not have significant correlation with weight reduction. The concentration of ANP correlated positively with the diameter of the inferior vena cava (r = 0.70, P < 0.05) after dialysis, but not before dialysis. The concentration of ANP before or after haemodialysis or its change during dialysis did not correlate with any other biochemical parameter. The results show that plasma ANP level is decreased after volume reduction in patients with chronic renal failure, whereas other hormonal systems are unresponsive. However, plasma concentration of ANP seems to have no role in estimating dry weight in chronic haemodialysis patients.

Topics: Adult; Aged; Aldosterone; Atrial Natriuretic Factor; Body Weight; Catecholamines; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Neurotransmitter Agents; Renal Dialysis; Renin; Ultrasonography; Vasopressins

Adrenomedullin (AM), a novel vasodilator peptide, is produced by C-terminal amidation reaction of AM-glycine. AM-glycine, an intermediate form of AM (iAM), is processed from pro AM. AM circulating in the human blood stream was found to consist of an amidated mature form (mAM) and iAM. Biological activity is exerted only by mAM.. To investigate the pathophysiological role of mAM in renal disease, we measured plasma concentrations of mAM as well as total AM (tAM), representing both mAM and iAM, in patients with various renal diseases. In addition, plasma ANP level was measured in all patients.. The concentrations of plasma mAM in renal failure with dialysis (2.1 +/- 0.2 fmol/ml, mean +/- SEM) and without dialysis (1.2 +/- 0.2) were significantly (p < 0.05) higher than those in control group (0.5 +/- 0.1). However, the plasma ANP level was increased only in renal failure patients with dialysis. Plasma mAM levels were significantly correlated positively with serum creatinine levels and negatively with hematocrit. No significant difference was noted in the ratio of mAM/tAM between renal failure patients and healthy subjects.. These results suggest that plasma mAM is increased in renal failure in relation to deterioration of renal function, while the amidation process of AM seems to be unaffected in patients with renal failure.

Topics: Adrenomedullin; Adult; Aged; Atrial Natriuretic Factor; Calcitonin Gene-Related Peptide; Creatinine; Erythropoietin; Female; Glomerulonephritis; Glycine; Hematocrit; Humans; Kidney Failure, Chronic; Linear Models; Male; Middle Aged; Peptides; Prodrugs; Recombinant Proteins; Renal Dialysis; Vasodilator Agents

This study has examined the association between circulating atrial natriuretic peptide (ANP), plasma cyclic GMP and urinary cyclic GMP in relation to hypertension and reduced renal function in 30 normotensives, in 30 patients with essential hypertension and in 22 patients with stable dialysis-independent chronic renal failure (CRF). Plasma ANP was significantly raised (about two-three-fold) in the CRF group compared with the hypertensive and normal groups; plasma cyclic GMP was also significantly raised in the CRF group (median group values: 4.6, 5.8 and 11.0 pmol/ml, respectively, for the normal, hypertensive and CRF groups). There were no significant differences in urinary cyclic GMP between the normotensives and hypertensives but urinary cyclic GMP was significantly reduced in the patients with CRF (median group values: 407.1, 450.9 and 247.8 pmol/min for the normal, hypertensive and CRF groups, respectively, P < 0.001). In the subjects with CRF, the clearance of cyclic GMP was reduced in proportion to the clearance of creatinine, but there was no significant difference in the fractional excretion of cyclic GMP (median group values: 78.1% in the normal group, 78.9% in the hypertensive group and 70.2% in the CRF group). In all groups, there was no association between circulating ANP and urinary cyclic GMP: By contrast, there was a positive association between plasma ANP and plasma cyclic GMP (r = 0.39 P < 0.001) that was independent of blood pressure or renal function. These results demonstrate that while a substantial amount of urinary cyclic GMP originates from the glomerular filtrate, to some extent, raised plasma ANP also contributes to the circulating levels of cyclic GMP. However, plasma cyclic GMP cannot be taken as a direct substitute for plasma ANP.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Cyclic GMP; Female; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged

The model of chronic renal failure (CRF) was made in 5/6 nephrectomized rats and Huangdan capsule was used to treat these rats. The levels of cyclic guanosine monophosphate (cGMP) and atrial natriuretic peptide (ANP) in plasma were examined. The results showed that Huangdan capsule could postpone the increase in the levels of cGMP and ANP, suggesting that by regulating the water and sodium metabolism, Huangdan capsule could ameliorate the glomerular filtration rate, and that Huangdan capsule could lower the levels of cGMP and ANP in plasma via body regulation.

Topics: Animals; Atrial Natriuretic Factor; Cyclic GMP; Drug Combinations; Drugs, Chinese Herbal; Glomerular Filtration Rate; Kidney Failure, Chronic; Male; Rats; Rats, Sprague-Dawley

In 15 patients with end-stage renal failure and proven coronary heart disease, profile haemodialysis with decreasing ultrafiltration rate and hyperionic, decreasing dialysate solute concentration was compared with conventional, extracorporeal bicarbonate haemodialysis (Na+D = 138 mmol/l). Body fluid distribution and the release of vasoactive hormones (plasma renin activity, aldosterone, norepinephrine, epinephrine, and atrial natriuretic peptide) were investigated. Haemodialysis with constant ultrafiltration rate and constant dialysate composition (A) was followed by two dialysis profiles: decreasing ultrafiltration rate (B) and additional hyperionic, decreasing dialysate sodium concentration (C). In all 15 patients, the dialysis procedures (A) - (C) were used for 2 weeks each with six sessions, the last being taken for investigation. Body fluid distribution was calculated. In patients with serum sodium above 136 mmol/l, the conventional dialysis (A) as well as the Uf profile (B) showed a net fluid shift from extracellular volume (ECV) to intracellular volume (ICV). Using the profile with hyperionic, decreasing Na+D (C), the reverse fluid shift with decreasing ICV was achieved not only in those with serum Na+ <136 mmol/l, but also in those with serum Na+ > or = 136 mmol/l. The release of vasoactive hormones decreased already at profile haemodialysis (B) compared with (A) and was further reduced in (C). These results would suggest, profile dialyses B and C to have less impact on the cardiovascular system in elderly patients assuming higher patient comfort compared with the standard dialysis procedure. A higher benefit was obtained in C compared with B, presumably due to the additional prevention of the ICV shift and plasma volume depletion in patients with initial serum sodium > or = 136 mmol/l using transiently hyperionic Na+D. These results show that in elderly patients, hyperionic profile haemodialysis (Na+D > Na+S) had less impact on cardiovascular regulation than conventional bicarbonate dialysis.

Topics: Aged; Aging; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Coronary Disease; Epinephrine; Extracellular Space; Female; Humans; Intracellular Fluid; Kidney Failure, Chronic; Male; Middle Aged; Norepinephrine; Renal Dialysis; Renin; Sodium; Ultrafiltration

It has been suggested that renal disease is characterized by the presence of resistance to the natriuretic effects of atrial peptide (ANP). In this study, plasma ANP (pANP) and renal function were evaluated during stepwise infusion of low ANP doses (2, 4, 8, and 16 ng/kg per min) in glomerulonephritic patients with (CRF) or without (GN) moderate renal failure, and in normal subjects (NOR), kept at low-sodium diet (LSD; 35 mEq NaCl/day). To assess the physiological ANP levels, pANP was also measured in the three groups after normal-sodium diet (NSD; 235 mEq NaCl/day). ANP did not affect systemic and renal perfusion at any of the doses tested; a significant increment of GFR was observed only in NOR and GN. The 2-, 4-, and 8-ng/kg doses increased pANP to values overlapping the physiological concentrations measured at NSD; this was associated with a dose-dependent increment of urinary excretion of sodium (UNaV) that reached analogous levels in the three groups. ANP accounted for approximately 40% of the UNaV increment evoked by NSD in patients and in normal subjects. The 16-ng/kg dose led to supraphysiological levels that induced a similar marked enhancement of UNaV (from the basal value of 0.12 +/- 0.02 to 0.42 +/- 0.08 mEq/min in CRF, from 0.13 +/- 0.02 to 0.73 +/- 0.08 in GN, and from 0.09 +/- 0.02 to 0.49 +/- 0.11 in NOR). In CRF, the normal natriuretic response to the highest dose was caused by a larger increase of fractional UNaV that was strictly dependent on the greater pANP increment, as demonstrated by similar changes in the fractional excretion of cGMP, and, in part, on the greater aldosterone decrease. In all groups, ANP also induced a dose-dependent urinary loss of phosphate, potassium, and urea, resulting in a significant 15 to 25% decrease in the plasma levels. Thus, in GN and CRF patients, ANP plays a significant role in the renal handling of sodium; moreover, the achievement of low supraphysiological pANP levels leads to a conspicuous natriuresis associated with unique extranatriuretic effects.

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Chronic Disease; Cyclic GMP; Diet, Sodium-Restricted; Diuresis; Dose-Response Relationship, Drug; Glomerulonephritis; Hemodynamics; Humans; Kidney Failure, Chronic; Male; Natriuresis; Reference Values; Renal Circulation

The objective of the study was to assess the evolution of renin, angiotensin II, atrial natriuretic factor (ANF) and blood pressure (BP) in the first trimester following renal transplantation in man Thirty-two recipients were investigated for 3 months post-transplantation. Twenty had a history of hypertension with moderate cardiac hypertrophy. Thirty-one retained their native kidneys. Five kidney donors had a history of mild hypertension. The recipients were perioperatively volume-expanded with 0.9% saline and diuresis was maintained for 48 h with furosemide and dopamine. The sodium intake was 25 mEq/24 hours. Prophylactic immunosuppressive therapy was antilymphocyteglobulins (25 cases), or anti-LFA1 (7 cases) and maintenance therapy was cyclosporine-prednisone (8 cases), or cyclosporine-prednisone-azathioprine (24 cases). Mean BP, serum creatinine, urinary sodium excretion (UNA) and hormonal (renin, angiotensin II and ANF) parameters were collected every other day for the first week after transplantation and then twice monthly. Twenty (62.5%) patients developed hypertension and hypertension was more frequent in patients with a delayed graft function, than in patients with immediate good graft function (10/20 vs. 4/12, p < 0.05%). Both hypertensive (group HBP) and normotensive (group NBP) patients had similar very low renin and angiotensin II plasma levels, after an initial early peak. Analysis of covariance with multiple regression analysis showed that in the HBP patients, BP was negatively correlated with UNA (p = 0.02) and positively with plasma ANF (p < 0.01). The normal BP patients also showed a correlation between BP and UNA, although it was limit of statistical significance (p = 0.05); there was no correlation between ANF and BP. We conclude that the RAS is rapidly depressed after renal transplantation and does not interfere with BP regulation. The hypertension in the early stage of post-transplantation varies inversely with the urinary sodium excretion. The defective sodium excretion, which dominates the effect of the low sodium diet, results in volume overload, increased ANF and volume-dependent hypertension.

Topics: Adult; Angiotensin II; Atrial Natriuretic Factor; Blood Pressure; Creatinine; Drug Therapy, Combination; Female; Follow-Up Studies; Graft Rejection; Humans; Hypertension; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Radioimmunoassay; Regression Analysis; Renin; Sodium

Factors affecting cardiac function in dialysis patients include arterial blood pressure, anaemia, intravascular volume, and the arteriovenous (a-v) access. Cardiac failure has been directly attributed to dialysis a-v access in several cases. The contribution of the a-v access to cardiac performance has been tested, in the past, by a short manual compression on the fistula, but this technique has obvious limitations.. The present study examined prospectively the effect of dialysis a-v access on both cardiac function and various hormonal responses. Ten patients (age, mean +/- SD, 59.6 +/- 12.3) with end-stage renal failure being prepared for chronic dialysis therapy were included. All patients underwent an echocardiographic study before and 2 weeks after the creation of the a-v access. Plasma atrial natriuretic peptide (ANP), plasma renin activity (PRA), and plasma aldosterone were measured at the same time periods.. Following the creation of the a-v fistula or graft, shortening fraction increased by 15.8 +/- 6.3% (P < 0.01), stroke volume increased by 21.9 +/- 5.3% (P < 0.01), ejection fraction increased by 10.6 +/- 4.5% (P < 0.02), cardiac output increased by 19.0 +/- 6.9% (P < 0.02), and cardiac index increased by 18.3 +/- 7.1% (P = 0.05). Systemic vascular resistance decreased by 23.5 +/- 7.1% (P < 0.01). There was no change in blood pressure, heart rate, weight, haemoglobin or serum creatinine. ANP increased by 83.7 +/- 17.0% following the a-v access operation (P < 0.001), PRA decreased by 41.2 +/- 10.0% (P < 0.05), and plasma aldosterone did not change. None of the patients developed overt high-output cardiac failure.. This study shows that at least in the short term following the creation of a dialysis a-v access, a mild state of volume overload develops, which is offset by the ¿unloading' effect of the decreased peripheral vascular resistance; the latter is probably mediated by secretion of ANP in response to atrial stretching.

Topics: Adult; Aged; Arteriovenous Fistula; Atrial Natriuretic Factor; Catheters, Indwelling; Creatinine; Female; Hematocrit; Hemodynamics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Renal Dialysis; Renin

The purpose of this study was to evaluate the effect of hemodialysis on the plasma concentration of atrial and brain natriuretic peptides, and to determine the two-dimensional echocardiographic parameters affecting the changes of plasma atrial and brain natriuretic peptide levels in patients with chronic renal failure.. Brain natriuretic peptide has been found in human cardiac tissue and increases in patients with congestive heart failure. However, the factors that stimulate the secretion of plasma brain natriuretic peptide have not yet been fully clarified.. In 15 patients with chronic renal failure, plasma atrial and brain natriuretic peptide levels and two-dimensional echocardiographic parameters were measured before and after each session of hemodialysis.. Plasma atrial natriuretic peptide levels significantly decreased from 367 +/- 537 pg/mL to 138 +/- 167 pg/mL after hemodialysis (p < 0.01). However, plasma brain natriuretic peptide levels did not significantly change after hemodialysis. Left atrial dimension significantly decreased (41.1 +/- 6.6 vs. 36.3 +/- 6.2 mm, p < 0.01) and left ventricular end-diastolic dimension slightly decreased after hemodialysis (57.0 +/- 10.3 vs. 55.7 +/- 9.9 mm, p < 0.05). The decrease of left atrial dimension was greater than that of left ventricular end-diastolic dimension (4.9 +/- 1.6 vs. 1.3 +/- 0.6 mm, p < 0.05). Plasma brain natriuretic peptide levels significantly correlated with fractional shortening both before and after hemodialysis (r = 0.65, p < 0.05).. Plasma atrial natriuretic peptide levels significantly decreased as the right and left atrial overloads decreased, and plasma brain natriuretic peptide levels did not significantly decrease after hemodialysis. Plasma brain natriuretic peptide levels were not significantly influenced by acute hemodynamic change, such as hemodialysis. However, plasma brain natriuretic peptide levels were significantly correlated with basic cardiac function.

Topics: Adult; Aged; Atrial Natriuretic Factor; Echocardiography; Female; Humans; Kidney Failure, Chronic; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Renal Dialysis; Time Factors

The usefulness of plasma atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), and cyclic guanosine 3',5'- monophosphate (cGMP) as markers of fluid overload was examined in hemodialysis (HD) patients without diabetes mellitus. Plasma concentrations of ANP, BNP, CNP, and cGMP all decreased significantly during HD. Before HD, there was a strong correlation between plasma concentrations of ANP and those of BNP, and plasma concentrations of cGMP correlated significantly with those of all three natriuretic peptides. The cardiothoracic ratio also correlated significantly with plasma concentrations of ANP and those of BNP before HD. Systolic blood pressure correlated significantly only with plasma concentrations of CNP, both before and after HD. Changes in body weight during HD correlated only with those in plasma ANP; there was thus no correlation between changes in body weight and those in plasma CNP. In conclusion, only plasma ANP is a useful marker of the proper volume and dry weight of HD patients. Furthermore, CNP may participate in cardiovascular regulation in HD patients in a manner different from those of ANP and BNP.

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Female; Heart Rate; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

It has been observed that while most hypertensive hemodialysis patients normalize their blood pressure with volume removal, there is a population of hemodialysis patients whose hypertension is refractory to volume removal. Our hypothesis is that such patients are still volume overloaded posthemodialysis and are not at a "true" dry weight. This study used atrial natriuretic peptide (ANP) assays (as a marker of hydration status) to study this hypothesis. Three groups of patients were studied: normotensive hemodialysis patients (n = 12; group 1), hypertensive hemodialysis patients who consistently normalize their blood pressure with fluid removal (n = 12; group 2), and hypertensive hemodialysis patients whose hypertension is refractory to fluid removal (n = 9; group 3). Plasma ANP levels were measured before and after hemodialysis by radioimmunoassay after extraction on Sep-Pac (Penninsula Laboratories, Belmont). On the day of study the predialysis mean arterial pressures in the three groups were 94.9 +/- 1.9 mm Hg in the normotensive group, 119.5 +/- 2.7 mm Hg in the dialysis-sensitive hypertension group, and 134.4 +/- 3.8 mm Hg in the dialysis-refractory hypertension group (P < 0.05 for comparisons between all groups). Mean arterial pressure did not change predialysis and postdialysis in the normotensive group (94.9 +/- 1.9 mm Hg to 93.1 +/- 1.8 mm Hg, respectively; P = 0.24), decreased in the dialysis-sensitive hypertension group (119.5 +/- 2.7 mm Hg to 100.8 +/- 3.7 mm Hg, respectively; P < 0.0001), and did not change in the dialysis-refractory hypertension group (134.4 +/- 3.8 mm Hg to 133.8 +/- 2.9 mm Hg, respectively; P = 0.77). Predialysis and postdialysis serum ANP levels were, respectively, 235.8 +/- 27.7 pg/mL and 237.8 +/- 36.2 pg/mL (P = 0.92) in the normotensive group, 809.2 +/- 295.5 pg/mL and 161.1 +/- 48.6 pg/mL (P = 0.03) in the dialysis-sensitive hypertension group, and 1,728.3 +/- 309.9 pg/mL and 1,936.1 +/- 359.1 pg/mL (P = 0.22) in the dialysis-refractory hypertension group. Mean predialysis ANP levels were higher in the dialysis-refractory hypertension group than in the dialysis-sensitive hypertension group (1,728.3 +/- 309.9 pg/mL v 809 +/- 359.1 pg/mL; P = 0.048). Mean prehemodialysis ANP in all hypertensive patients (n = 21) was higher (1,203.1 +/- 232.9) than in the normotensive patients (235.8 +/- 27.7) (P = 0.004). In conclusion, our findings are consistent with a hypothesis that inadequate removal of excess volume during hemodia

Topics: Adult; Analysis of Variance; Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Blood Volume; Female; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

The renal response to sodium restriction was evaluated, and the concurrent changes of the plasma levels of aldosterone (ALDO) and atrial natriuretic peptide (ANP), in healthy patients (NOR), in normotensive patients with non-nephrotic chronic glomerulonephritis and normal renal function (GN), and in patients with glomerulonephritis and moderate renal failure (GFR, 41 +/- 4 mL/min; CRF). The three groups were studied for 1 wk after changing from a normal-sodium diet (NSD, 235 mEq NaCl/day) to a low-sodium diet (LSD, 35 mEq NaCl/day). All patients reached a steady sodium balance within the 4th and 5th day of LSD with an analogous cumulative loss of sodium. After salt restriction, the fractional urinary sodium excretion diminished by the same extent in the three groups, whereas the fractional free-water generation, measured during water diuresis, did not vary in NOR and markedly decreased in GN and CRF. Plasma levels of ALDO were similar in all groups at NSD and similarly increased during LSD. In GN and CRF, as compared to NOR, ANP levels were higher at NSD and decreased by a minor extent during LSD. Notably, in GN and CRF, but not in NOR, the attainment of the new sodium balance after sodium restriction was preceded by a significant parallel reduction of blood pressure and GFR; the GFR decline was secondary to a major decrement of RPF so that filtration fraction (FF) increased. It was concluded that in NOR, distal tubular effects of ANP and ALDO account for the attainment of sodium balance during LSD. As a difference, both GN and CRF patients achieve the new sodium balance primarily through hemodynamic changes: the renal hypoperfusion secondary to a decrease in blood pressure that diminishes the filtered load of sodium, and the increase of FF that enhances the proximal tubular sodium reabsorption. This abnormal response seems related to both the minor suppression of ANP and the increased salt-sensitivity of blood pressure that are likely the result of the presence of volume expansion.

Topics: Adaptation, Physiological; Adult; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Diet, Sodium-Restricted; Humans; Kidney; Kidney Diseases; Kidney Failure, Chronic; Kidney Glomerulus; Male; Treatment Outcome

Factors related to atrial natriuretic peptide (alpha-ANP) regulation and its potential impact on excretory transplant function were examined in a prospective cohort study of 20 patients with end-stage renal disease over 21 days after allogenic kidney transplantation. Depending on posttransplant graft function, patients were separated into those with primary renal function (PF group, n = 10) and posttransplant acute renal failure (ARF group, n = 10). ANP concentrations were markedly elevated in both PF and ARF immediately after renal transplantation, even when compared with the pretransplant dialysis phase (PF group: 939 +/- 467 pg/ml; ARF group: 648 +/- 306 pg/ml, on 3rd postoperative day; "normals': 72 +/- 35 pg/ml). Whilst ANP levels were persistently elevated in patients with acute renal failure, there was a steady decrease in plasma concentrations in patients with primary renal function (PF: 270 +/- 122 pg/ml on 21st day). ANP concentration correlated with endogenous creatinine clearance (rz = 0.56, p < 0.01, PF group). Moreover, there was a greater correlation between ANP levels and postoperative hydration status, measured as central venous pressure or the difference from predialysis dry weight (rz = 0.79 and rz = 0.74, p < 0.01, PF group). Systolic blood pressure was also positively correlated with ANP concentrations. Together, these factors accounted for a total correlation coefficient of r = 0.87 (p < 0.001) in multiple regression analysis. No significant relation was found between plasma ANP levels and total or fractional sodium excretion or free water clearance. With the restoration of renal function most vasoactive hormones (renin-aldosterone system, catecholamines, vasopressin) decreased towards normal values, whilst ANP plasma concentrations remained elevated.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Catecholamines; Central Venous Pressure; Cohort Studies; Creatinine; Cyclic GMP; Female; Humans; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Postoperative Period; Prospective Studies; Renin; Transplantation, Homologous; Vasopressins

Patients with chronic renal failure show almost equal levels of sodium excreted in the urine as healthy subjects through an increase of the fractional excretion sodium (FE(Na)). The mechanisms of this adaptation, however, are unknown. Recently, urinary arginine vasopressin (AVP) has been shown to inhibit the antidiuretic action of plasma AVP in the collecting ducts of rabbits and rats. In this article, the roles of plasma and urinary AVP are examined with other hormones in the sodium excretion of 57 patients with chronic renal disease. The fractional excretion of AVP, plasma atrial natriuretic peptide (ANP) and endothelin-1 (ET-1), urinary ET-1, and FE(ET-1) correlated with the decrease of creatinine clearance (Ccr). Multiple and stepwise regression analyses showed that FE(AVP) is the major dependent determinant for FE(Na) (adjusted r2 = 0.78). These results suggest that the increase of AVP excretion per remaining nephron could be a cause of the increase of FE(Na) in patients with renal failure. Although plasma AVP works as an antidiuretic hormone, urinary AVP serves as an intrinsic diuretic, especially in patients with chronic renal failure.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Arginine Vasopressin; Atrial Natriuretic Factor; Child; Endothelin-1; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Regression Analysis; Sodium

Left ventricular hypertrophy is very prevalent among patients with renal insufficiency. Known hypertrophic factors, such as systemic hypertension, do not adequately account for the prevalence of left ventricular hypertrophy in these patients. Circulating growth factors may stimulate cardiomyocyte growth and contribute to the development of left ventricular hypertrophy. The effects of sera from patients with (n = 30) and without (n = 5) chronic renal insufficiency on the growth of cultured adult cardiomyocytes were compared. An adult rat cardiomyocyte primary culture system was established with a high purity of cardiomyocyte population as confirmed by immunocytochemical staining of cardiac contractile proteins. Myocytes responded with increased [3H]thymidine incorporation when treated with angiotensin II, epidermal growth factor, hydrocortisone and insulin, and with increased [3H]phenylalanine incorporation when treated with parathormone, isoproterenol, phenylephrine and insulin. Renal insufficiency serum stimulated [3H]thymidine incorporation was 1.5 times that of the control (P < 0.02) and also tended to increase incorporation of [3H]phenylalanine compared to the control (P = N.S.). Increased [3H]thymidine incorporation by renal insufficiency serum did not correlate with serum insulin, parathormone or glucose in the renal insufficiency patients. A quantitative reverse transcriptase polymerase chain reaction (RT-PCR) method was used to measure renal insufficiency serum-induced atrial natriuretic peptide mRNA expression in cultured cardiomyocytes. Atrial natriuretic peptide (ANP) mRNA was increased 1-3-fold in cardiomyocytes treated with renal insufficiency sera in comparison to control sera. These data suggest that circulating growth factor(s) may contribute to the development of cardiac hypertrophy in patients with renal insufficiency.

Topics: Animals; Atrial Natriuretic Factor; Cell Division; Cells, Cultured; Gene Expression; Growth Substances; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Myocardium; Phenylalanine; Rats; Rats, Sprague-Dawley; RNA, Messenger; Thymidine; Tritium

To assess the effect of recombinant human erythropoietin (EPO) on the factors regulating blood pressure (BP), we determined the hemoglobin level (Hgb), blood viscosity (BV), plasma renin activity (PRA), plasma concentrations of aldosterone (PAC), adrenaline (Ad), noradrenaline (NAd), and atrial natriuretic peptide (ANP), and serum and intracellular concentrations of cations before and after 3 months of EPO treatment (40 units/kg/week of EPO intravenously after each hemodialysis session) in 11 patients undergoing maintenance hemodialysis. Intracellular sodium concentration ([Na+]i) was measured using erythrocytes with flame photometry. EPO treatment was associated with significant increases in Hgb (7.1 +/- 1.4 to 8.4 +/- 1.8 g/dl, p<0.01), mean BP (103 +/- 11.4 to 116 +/- 19.9 mmHg, p<0.01), [Na+]i (4.99 +/- 0.78 to 6.22 +/- 0.96 mmol/l, p<0.01) and BV (1.39 +/- 0.14 to 1.53 +/- 0.18 c.p., p<0.05), but no significant alteration in PRA, PAC, Ad, NAd, ANP, or in the serum concentration of Na+, K+, and Ca2+. The changes in mean BP (deltaMBP) were significantly correlated with delta[Na+]i (R=0.676, p=0.022) and deltaBV (R=0.668, p=0.034), but not with deltaHgb. By multiple regression analysis, delta[Na+]q and deltaBV independently contributed to deltaMBP; deltaMBP=2.27 X delta[Na+]i+32.2 X deltaBV +3.37 (R=0.695). These data suggest that intracellular sodium accumulation as well as increased blood viscosity may be independently involved in the blood pressure elevation after EPO treatment in patients under maintenance hemodialysis. We found no evidence supporting a role of circulating hormonal factors, such as the renin-angiotensin system, adrenaline, or ANP, in the change in blood pressure.

Topics: Aged; Aldosterone; Anemia; Atrial Natriuretic Factor; Blood Pressure; Blood Viscosity; Calcium; Cations; Epinephrine; Erythrocyte Count; Erythrocytes; Erythropoietin; Female; Hematocrit; Hemoglobins; Humans; Hypertension, Renal; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Norepinephrine; Potassium; Regression Analysis; Renal Dialysis; Renin; Sodium

In order to clarify the relationship between vasoactive substances and changes in blood pressure (BP) during hemodialysis (HD) in patients with end-stage renal disease, we measured plasma renin activity (PRA), plasma concentration of aldosterone (PAC), and the plasma concentrations of epinephrine (E), norepinephrine (NE), dopamine (DA) and atrial natriuretic peptide (ANP) in patients on HD. Fourty-eight patients, consisting of 24 males and 24 females, were included in this study. Their mean age was 63.8 years, and their mean HD duration was 55.9 months. In 9 patients without diabetes mellitus (DM) and whose BP was stable during HD, PRA and plasma concentrations of E and NE increased significantly during HD, and that of DA decreased during HD. In 9 patients without DM and whose BP fell during HD, PRA and plasma concentrations of E and NE showed no significant response to the decrease in body weight during HD. In spite of the increase in NE concentration during HD in 8 patients without DM and whose BP was usually hypotensive, BP remained low. This might be due to the decrease in sensitivity of their peripheral autonomic receptors to NE. In the 9 patients with DM whose BP was stable and 13 patients with DM whose BP fell during HD, vasoactive substances made almost no effective response to the decrease in body weight during HD. In conclusion, we must take into consideration the fact that both hypotensive patients during HD and diabetic patients on HD might exhibit an abnormal response of their vasoactive substances.

Topics: Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Dopamine; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Renin

Studies were performed to examine the changes of renal ANF second messenger guanosine 3',5'-cyclic monophosphate (cGMP) responses and receptor properties in chronic renal failure (CRF). Five-sixths-nephrectomized and sham-operated Wistar rats were used. The glomerular filtration rate was decreased in the five-sixths-nephrectomized rats, which also had significantly higher plasma blood urea nitrogen and plasma atrial natriuretic factor (ANF) levels (148.5 +/- 10.2 vs. 115.7 +/- 7.3 pg/ml, P = 0.01) than the sham rats. In vitro ANF-stimulated cGMP accumulations in glomeruli of five-sixths-nephrectomized rats were higher than controls. Radioligand-binding experiments showed downregulation of the total ANF receptor in both acid and nonacid wash CRF glomeruli (nonacid wash: 189 +/- 25 vs. 362.8 +/- 52.8 fmol/mg protein, P < 0.05; acid wash: 449.8 +/- 67 vs. 652.7 +/- 52.5 fmol/mg protein, P < 0.05). No change in receptor densities was observed in the des(Gln18,Ser19,Gly20,Leu21)atrial natriuretic peptide-(4--23)-NH2-resistant receptors between sham and CRF rat glomeruli. Therefore, downregulation of ANF clearance receptors exists in CRF rat glomeruli, and this is associated with the exaggerated ANF-stimulated cGMP response in these CRF glomeruli. Hypersensitivity of CRF rat to ANF, together with high plasma ANF levels and downregulation of clearance receptor, may contribute to increased sodium excretion in CRF.

Topics: Animals; Atrial Natriuretic Factor; Binding, Competitive; Cyclic GMP; Down-Regulation; Glomerular Filtration Rate; Kidney Failure, Chronic; Male; Nephrectomy; Rats; Rats, Wistar; Receptors, Atrial Natriuretic Factor; Second Messenger Systems

Plasma brain natriuretic peptide (BNP) levels have been reported to increase in patients with heart failure and end-stage renal disease (ESRD); however, little is known about molecular forms of plasma BNP that increase in these diseases. In the present study, we analyzed the molecular forms of plasma BNP in ESRD patients of both before (pre-) and after (post-) hemodialysis (HD) state. The plasma extract was analyzed by gel filtration on a TSK-GEL G2000 SW column followed by a RIA for both BNP and atrial natriuretic peptide (ANP). In the pre-HD patients, a 14- to 2300-fold increase in plasma level of immunoreactive (ir-) BNP was observed when compared to normal controls. A ratio of BNP-32 to g-BNP (pro BNP) in plasma from the patients was much larger than that in plasma from normal subjects, indicating that the high plasma level of ir-BNP level in the patients on HD largely results from a marked increase in BNP-32. HD significantly (P < 0.01) lowered the plasma levels of both BNP-32 and g-BNP with a greater reduction in BNP-32 than in g-BNP. Whereas, a-ANP was a main molecular form of plasma ANP in both pre- and post-HD plasma. These results suggest that plasma BNP-32 plays an important role in the sodium-fluid balance and that secretion and metabolism of BNP may differ from those of ANP in the HD patients.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Chromatography, Gel; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Radioimmunoassay; Renal Dialysis

Since it was first discovered in the early 1980s, the role of atrial natriuretic peptide (ANP) in the control of fluid and electrolyte balance and blood pressure has been extensively studied in both health and disease. We report here a study of ANP and its relationship to corresponding changes in right atrial pressure (RAP) in patients with chronic renal failure (CRF) on haemodialysis compared to healthy controls. Although there was a positive correlation between RAP and ANP in both groups, the changes in ANP following changes in RAP between the two groups were not statistically significant. A unique observation was the response of RAP to changes in posture, with RAP falling significantly as expected in healthy controls in contrast to the exceptional absence of a significant fall in patients with CRF. Healthy controls demonstrated appropriate postural changes in plasma renin activity (PRA) despite marked suppression of PRA levels due to salt loading, in complete contrast to patients with CRF who, despite chronic fluid overload and elevated levels of ANP, continued to have grossly elevated PRA levels that failed to change significantly in response to changes in posture.

Topics: Atrial Function, Right; Atrial Natriuretic Factor; Catheterization, Swan-Ganz; Heart Rate; Humans; Kidney Failure, Chronic; Male; Middle Aged; Posture; Renal Dialysis; Renin; Sodium Chloride

The effects of hormone stimulation on atrial natriuretic factor (ANF) release in atria were studied in experimental renal failure rats. In vitro experiments were done in two groups of male Wistar rats. Group 1 rats were sham operated, and group 2 rats were subjected to 5/6 nephrectomy. Overall glomerular filtration rate was significantly reduced (1.98 +/- 0.10 vs. 0.75 +/- 0.05 ml/min, p < 0.001) in nephrectomized rats. These rats were also mildly uremic [blood urea nitrogen (BUN): 18 +/- 0.6 vs. 60 +/- 3.9 mg/dl p < 0.001]. The right atria of partially nephrectomized and sham-operated rats were isolated and perfused in a modified Langendorff apparatus to measure ANF release rate. Experiments were done in two phases. In the initial phase, spontaneous release of ANF was measured. In the second phase, angiotensin II (10(-6) M), vasopressin (10(-6) M) or endothelin (ET 1; 10(-6) M) were added into the perfusate. Spontaneous ANF release by the atria of renal failure rats was significantly elevated compared to intact rats. A significant positive correlation was found between ANF release rate and BUN (r = 0.65, p < 0.01). This suggests that the increase in ANF release by the atria of chronic renal failure (CRF) rats is related to the severity of renal impairment. Angiotensin II, vasopressin and endothelin induced exaggerated increases in ANF release by the atria of CRF rats. These results show that a shift in stimulus response curve is present and can contribute to the observed increase in plasma ANF levels in CRF rats.

Topics: Angiotensin II; Animals; Atrial Natriuretic Factor; Blood Urea Nitrogen; Endothelins; Glomerular Filtration Rate; Heart; Heart Atria; Hormones; Kidney Failure, Chronic; Male; Nephrectomy; Rats; Rats, Wistar; Stimulation, Chemical; Vasopressins

Blood pressure regulation during intermittent hemodialysis treatment involves many different mechanisms. Eight normotensive patients without antihypertensive drugs on intermittent hemodialysis treatment, mean age 50 years, were studied with 24-hour blood pressure measurements. Atrial natriuretic peptide (ANP) and neuropeptide Y (NPY) were determined concomitantly. Eight control individuals matched for age and sex were investigated in the same way. A significant increase of both systolic and diastolic blood pressure, heart rate and pathological circadian rhythm was seen among the dialysis patients. High levels of ANP were found before and after dialysis. NPY showed steady state levels through the 24 hours and did not differ between the two groups. Overhydration is a probable cause of the disturbed blood pressure regulation and increased ANP-values.

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Neuropeptide Y; Peptides; Renal Dialysis

Topics: Animals; Atrial Natriuretic Factor; Brain; Humans; Hyponatremia; Inappropriate ADH Syndrome; Kidney Failure, Chronic; Vasopressins; Water-Electrolyte Balance

Brain natriuretic peptide (BNP) is a polypeptide hormone which is homologous with atrial natriuretic peptide (ANP). Since the 2 hormones partially share common secretory regulation we simultaneously assessed plasma BNP and ANP in patients with chronic glomerulonephritis without apparent cardiac involvement. Blood samples were taken from patients with serum creatinine (Cr) 0.5-1.2 mg/dl (normal renal function), patients with Cr > 1.2 mg/dl (chronic renal failure) and dialysis patients. BNP did not correlate with serum Cr, which indicated our antibody did not recognize accumulated metabolites due to decreased renal function. BNP and ANP decreased after dialysis-(p < 0.01). Changes of BNP during HD correlated with changes in body weight (p < 0.05). Plasma BNP concentrations were 12.0 +/- 22.0 pg/ml in patients with normal renal function, 17.6 +/- 23.4 pg/ml in chronic renal failure, and 91.5 +/- 93.5 in dialysis patients (p < 0.05 compared with patients with normal renal function). Plasma BNP/ANP ratios were 0.507 +/- 0.646 in patients with normal renal function, 0.392 +/- 0.842 in chronic renal failure, and 0.573 +/- 0.431 in dialysis patients (p < 0.05, compared with chronic renal failure). Increased ANP in chronic renal failure and dialysis indicates volume overload on atrium. In contrast, BNP increased only in dialysis patients, which indicates differences of hemodynamic stress in chronic renal failure and dialysis. We conclude that simultaneous measurements of plasma BNP and ANP further discriminate salt-water and hemodynamic abnormalities in dialysis patients.

Topics: Adult; Aged; Atrial Natriuretic Factor; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Renal Dialysis

An attempt was made to clarify whether the molecular forms of atrial natriuretic peptide (ANP) in the plasma of stable hemodialysis patients differ from those of healthy volunteers, and whether the ANP molecular forms in plasma might change during hemodialysis treatment. Ten stable hemodialysis patients with no clinical signs of cardiac disease were treated for 4 hours by a hollow fiber-type dialyzer. Plasma ANP concentrations before dialysis were 210 +/- 101.6 pg/ml (mean +/- SD), which were significantly higher than that of volunteers (59.2 +/- 37.2 pg/ml, n = 25). They were significantly decreased to 71.6 +/- 60.1 pg/ml after dialysis. Molecular patterns of ANP were measured by gel permeation chromatography and reverse-phase high performance liquid chromatography. Immunoreactive alpha-ANP peaks of GPC, which co-migrated with authentic alpha-, beta-, and gamma-ANP, were supposed to be alpha-, beta-, and gamma-ANP. The plasma of four patients contained a beta-ANP peak before dialysis, and three of the four still contained a beta-ANP peak after dialysis. These results showed that the middle-molecular-weight ANP, which co-migrated with authentic beta-ANP and is supposed to be beta-ANP, may particularly be secreted in clinically stable hemodialysis patients.

Topics: Adult; Aged; Atrial Natriuretic Factor; Chromatography, Gel; Chromatography, High Pressure Liquid; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Molecular Structure; Radioimmunoassay; Renal Dialysis

The potential role of atrial natriuretic factor (ANF) in blood pressure (BP) drops during hemodialysis (HD) has been examined in 30 patients with end-stage chronic renal failure. Echocardiographic measurements and evaluation of cardiac parasympathetic function were performed prior to HD sessions, simultaneously with hormonal determinations. The plasma ANF level was correlated with the peak value of the E wave and the Doppler index of the left ventricular preload and was more elevated in 'denervated' than in intact patients. During the HD sessions, the BP fell in 18 patients (group 1) and remained stable in 12 others (group 2), despite similar weight losses. Both groups differed by the basal values of plasma ANF, greater in group 1 than in group 2 (100.0 +/- 13.3 vs. 65.7 +/- 3.4 fmol/ml; p < 0.05). The magnitude of plasma ANF decrease was identical in both groups despite the BP decrease in group 1 at the end of the session. These results suggest that the ANF release depends not only on hemodynamics but also on cardiac innervation in dialyzed patients and that high plasma ANF levels are implied in the BP drops during HD session.

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Echocardiography, Doppler; Female; Heart; Hemodynamics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Parasympathetic Nervous System; Renal Dialysis; Ventricular Function, Left

1. Plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptides (BNP) were measured, along with left and right atrial and left ventricular volumes, in eight patients with chronic renal failure before and after the removal of 2.1 +/- 0.61 of fluid by ultrafiltration and again during volume repletion with intravenous sodium chloride solution (150 mmol/l saline) to restore body weight plus 0.5 kg. 2. Baseline levels of ANP (46.0 +/- 7.5 pmol/l) and BNP (22.0 +/- 4.4 pmol/l) were elevated above normal. There was a significant reduction in plasma ANP (26.5 +/- 4.7 pmol/l, P < 0.05) and BNP (19.1 +/- 4.9 pmol/l, P < 0.05)) following ultrafiltration. Changes in plasma ANP during ultrafiltration correlated significantly with changes in left atrial volume (r = 0.643, P < 0.05). 3. During volume repletion there was an exaggerated release of ANP (mean level post repletion 71.3 +/- 20.8 pmol/l) which was not paralleled by changes in BNP. Changes in BNP were small, showing no correlation with atrial or ventricular volumes during either ultrafiltration or volume repletion. 4. These findings indicate that in chronic renal failure without left ventricular dysfunction, moderate acute changes in volume status elict only small immediate responses in plasma BNP. Changes in plasma ANP are greater than BNP and more responsive to changes in left atrial volume.

Topics: Adolescent; Adult; Atrial Natriuretic Factor; Blood Volume; Cardiac Volume; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Renal Dialysis

Plasma levels of endothelin (ET) and atrial natriuretic peptide (ANP) are known to be elevated in patients on chronic hemodialysis. Since ET and ANP plasma levels are found to be raised in nonuremic diabetic versus nondiabetic subjects, we wanted to detect a possible difference in plasma levels of these hormones in diabetic versus nondiabetic patients who were on chronic renal replacement therapy. ET is a possible marker of increased vascular atherogenic activity. We measured plasma levels of ET and ANP pre- and posthemodialysis in 23 non-insulin-dependent (NIDDM) diabetic versus 23 nondiabetic patients who were matched according to age and time of day of hemodialysis, and who did not show clinical signs of overt cardiac decompensation. Mean plasma levels of ET and ANP did not differ in diabetic from nondiabetic patients, neither pre- nor postdialysis. In both patient groups, mean ET levels were twice the upper normal limit, did not change significantly pre- versus postdialysis, and did not correlate with blood pressure or with volume ultrafiltration during dialysis. Calcium channel blocker therapy was accompanied by a significant rise of ET pre- and postdialysis in nondiabetic patients but not in diabetic patients. In diabetic patients, ET plasma levels correlated positively with fructosamine levels as an indicator of short-term blood glucose control. Mean ANP plasma levels were about three times the upper normal limit and decreased significantly during dialysis, but this decrease correlated neither with volume ultrafiltration nor with blood pressure. In conclusion, we could not find a difference in plasma levels of ET and ANP for diabetic versus nondiabetic dialysis patients, but impaired short-term blood glucose control in diabetic and calcium channel blocker therapy in only nondiabetic dialysis patients showed concomitant increases in plasma ET levels and thus possibly different mechanisms of ET regulating pathways.

Topics: Aged; Atrial Natriuretic Factor; Blood Pressure; Calcium Channel Blockers; Diabetes Mellitus, Type 2; Endothelins; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

Plasma concentrations of atrial natriuretic peptide (ANP) and its second messenger cyclic guanosine-monophosphate (cGMP) were studied in 28 children and adolescents (1 to 19 years) on peritoneal dialysis and compared to 55 healthy children (1 to 20 years). Dialysate concentrations of the hormones were measured also in the patients. Plasma ANP was not significantly different in patients and controls (28.8 pmol/l [15.5-53.6 pmol/l] [median, lower and upper quartile] versus 26.3 pmol/l [19.9-31.8 pmol/l]). In seven children on peritoneal dialysis it exceeded an upper normal limit of 50 pmol/l, but it fell to normal values in four of them after forced fluid withdrawal. Plasma cGMP was elevated in the patients compared to the control children (1.6 nmol/l [1.1-1.7 nmol/l] versus 1.0 nmol/l [0.8-1.2 nmol/l]; p < 0.05). There were only weak correlations between plasma and dialysate concentrations of ANP and cGMP. Plasma concentrations of ANP seem to be elevated in children on peritoneal dialysis in case of fluid overload.

Topics: Adolescent; Atrial Natriuretic Factor; Child; Cyclic GMP; Female; Humans; Kidney Failure, Chronic; Male; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Radioimmunoassay; Reference Values; Water-Electrolyte Imbalance

Brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) plasma concentrations were measured in patients with dialysis-dependent chronic renal failure and in patients with coronary artery disease exhibiting normal or elevated left ventricular end-diastolic pressure (LVEDP) (n = 30 each). Blood samples were obtained from the arterial line of the arteriovenous shunt before, 2 h after the beginning of, and at the end of hemodialysis in patients with chronic renal failure. In patients with coronary artery disease arterial blood samples were collected during cardiac catheterization. BNP and ANP concentrations were determined by radioimmunoassay after Sep Pak C18 extraction. BNP and ANP concentrations decreased significantly (P < 0.001) during hemodialysis (BNP: 192.1 +/- 24.9, 178.6 +/- 23.0, 167.2 +/- 21.8 pg/ml; ANP: 240.2 +/- 28.7, 166.7 +/- 21.3, 133.0 +/- 15.5 pg/ml). The decrease in BNP plasma concentrations, however, was less marked than that in ANP plasma levels (BNP 13.5 +/- 1.8%, ANP 40.2 +/- 3.5%; P < 0.001). Plasma BNP and ANP concentrations were 10.7 +/- 1.0 and 60.3 +/- 4.0 pg/ml in patients with normal LVEDP and 31.7 +/- 3.6 and 118.3 +/- 9.4 pg/ml in patients with elevated LVEDP. These data demonstrate that BNP and ANP levels are strongly elevated in patients with dialysis-dependent chronic renal failure compared to patients with normal LVEDP (BNP 15.6-fold, ANP 2.2-fold, after hemodialysis; P < 0.001) or elevated LVEDP (BNP 6.1-fold, ANP 2.0-fold, before hemodialysis; P < 0.001), and that the elevation in BNP concentrations was more pronounced than that in ANP plasma concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Coronary Disease; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Renal Dialysis; Ventricular Pressure

1. The aim of this study was to determine plasma levels of N-terminal atrial natriuretic peptide and atrial natriuretic peptide in normal subjects and in patients with essential hypertension, cardiac transplant and chronic renal failure, using radioimmunoassays directed towards the mid-portion pro-atrial natriuretic peptide (31-67) and pro-atrial natriuretic peptide (1-30) of the N-terminal atrial natriuretic peptide and atrial natriuretic peptide (99-126). The circulating form(s) of the immunoreactive N-terminal atrial natriuretic peptide in plasma extracts has been investigated using all three radioimmunoassays by means of gel filtration chromatography to further clarify the major immunoreactive molecular circulating form(s) of N-terminal atrial natriuretic peptide in man. 2. The plasma level (mean +/- SEM) of N-terminal pro-atrial natriuretic peptide (31-67) in the normal subjects was 547.2 +/- 32.7 pg/ml (n = 36) and was significantly elevated in patients with essential hypertension (730.2 +/- 72.3 pg/ml, P < 0.025, n = 39), in cardiac transplant recipients (3214.0 +/- 432.2 pg/ml, P < 0.001, n = 9) and in patients with chronic renal failure (3571.8 +/- 474.1 pg/ml, P < 0.001, n = 11). Plasma levels of N-terminal pro-atrial natriuretic peptide (1-30) and atrial natriuretic peptide were similarly elevated in the same patient groups when compared with the mean plasma values in the normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Atrial Natriuretic Factor; Chromatography, Gel; Female; Heart Transplantation; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Peptide Fragments; Protein Precursors; Radioimmunoassay

1. C-type natriuretic peptide is a neuropeptide, which is also produced by the vascular endothelial cells. Plasma immunoreactive C-type natriuretic peptide concentrations in patients with various diseases have not yet been studied. 2. Plasma immunoreactive C-type natriuretic peptide concentrations were studied by radioimmunoassay in normal subjects, patients with congestive heart failure, non-dialysed patients with chronic renal failure and haemodialysis patients with chronic renal failure. The C-type natriuretic peptide levels were compared with the levels of atrial natriuretic peptide and brain natriuretic peptide. 3. Plasma immunoreactive C-type natriuretic peptide concentrations were greatly elevated in patients with chronic renal failure [non-dialysed, 13.0 +/- 4.2 pmol/l (mean +/- SEM), n = 9, P < 0.01 compared with normal subjects (4.4 +/- 0.4 pmol/l, n = 26); haemodialysis, 16.1 +/- 2.1 pmol/l, n = 13, P < 0.01], but not in patients with congestive heart failure (New York Heart Association Class II-IV, 3.0 +/- 0.7 pmol/l, n = 11, P > 0.05). Plasma immunoreactive atrial natriuretic peptide and brain natriuretic peptide concentrations were elevated both in patients with congestive heart failure and in haemodialysis patients with chronic renal failure. 4. Reverse-phase high performance liquid chromatography showed that immunoreactive C-type natriuretic peptide in plasma from normal subjects and haemodialysis patients was eluted in the positions of C-type natriuretic peptide-22 and -53. 5. These findings suggest that C-type natriuretic peptide is a non-cardiac circulating hormone and participates in the cardiovascular regulation in a different manner from atrial natriuretic peptide and brain natriuretic peptide.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Chromatography, High Pressure Liquid; Female; Heart Failure; Humans; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, C-Type; Proteins; Radioimmunoassay; Renal Dialysis

Adrenomedullin is a potent hypotensive peptide newly discovered in pheochromocytoma tissue by monitoring its elevating activity on platelet cAMP. We measured plasma concentration of adrenomedullin in patients with essential hypertension and chronic renal failure. As compared with normal subjects, plasma adrenomedullin was increased by 26% (P < 0.05) in hypertensives without organ damage and by 45% (P < 0.005) in those with organ damage. The increase in plasma adrenomedullin was more prominent in renal failure than in hypertension. Renal failure patients with plasma creatinine of 1.5-3, 3-6, and > 6 mg/dl had higher plasma adrenomedullin levels than healthy subjects by 78% (P < 0.05), 131% (P < 0.001), and 214% (P < 0.001), respectively. Moreover, adrenomedullin showed intimate correlations with norepinephrine, atrial natriuretic peptide, and cAMP in plasma (r = 0.625, P < 0.001; r = 0.656, P < 0.001; and r = 0.462, P < 0.001; respectively). Thus, plasma adrenomedullin is supposed to increase in association with changes in sympathetic nervous activity and body fluid volume in hypertension and renal failure. Considering its potent vasodilator effect, adrenomedullin may be involved in the defense mechanism preserving the integrity of the cardiovascular system in these disorders.

Topics: Adrenomedullin; Adult; Aged; Antihypertensive Agents; Atrial Natriuretic Factor; Cyclic AMP; Female; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Peptides

Many endocrine abnormalities were reported in patients with chronic renal failure (CRF), including elevated ANP, but little is known on ANP vaso-regulatory effects during exercise. This study is aimed to find whether plasma ANP rises during exercise in patients with CRF, as it does in normal subjects, and whether there is a difference between this response in both those groups. 36 subjects were studied, divided into three groups: I--CRF patients treated conservatively (nondialyzed), II--CRF patients, dialyzed, III--healthy subjects. Plasma ANP was measured at rest and then immediately after submaximal treadmill work load according to modified Bruce protocol with continuous ecg and blood pressure monitoring. In the CRF nondialyzed patients the metabolic equivalent (MET) was significantly lower than in the other groups. The myocardial oxygen consumption, estimated as double product quotient, was the lowest in the nondialyzed CRF patients. A significant increase of the plasma ANP was seen in all subjects studied, significantly higher in the CRF patients than in the control healthy subjects. No correlations were found between the plasma ANP level and other measured parameters.

Topics: Adult; Atrial Natriuretic Factor; Exercise Test; Humans; Kidney Failure, Chronic; Oxygen Consumption; Physical Exertion

The changes in haemoglobin concentration, haematocrit, plasma renin activity (PRA) and atrial natriuretic peptide (ANP) were studied in 10 haemodialysis patients with erythropoietin-associated hypertension. All patients received intravenously 1500 IU of recombinant human erythropoietin (rHuEPO) thrice weekly for 24 weeks. Treatment with rHuEPO induced significant rises in haemoglobin concentration (p < 0.001) and haematocrit (p < 0.01). However, the difference between post- and pretreatment levels of haemoglobin (delta Hb) was not correlated with that between post- and pre-treatment mean blood pressure (delta MBP). No correlation was found between delta Ht (difference between post- and pre-treatment values of haematocrit) and delta MBP. These results indicate that elevation of the haematocrit and haemoglobin concentration of haemodialysis patients does not necessarily lead to an increase in blood pressure. In these patients, no significant differences were observed in PRA and ANP, comparing pre-treatment values with those measured 4, 8, 12 or 24 weeks after commencing rHuEPO. This suggests that neither PRA nor ANP play a central role in the pathogenesis of rHuEPO-induced hypertension.

Topics: Adult; Atrial Natriuretic Factor; Erythropoietin; Female; Hematocrit; Hemoglobins; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Renin

The present study aimed to investigate whether brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), cortisol and thyroid hormone concentrations change during hemodialysis in patients with chronic renal failure. Blood samples were withdrawn in 30 patients with chronic renal failure before hemodialysis, 2 hours after the beginning and at the end of hemodialysis. ANP and BNP concentrations were determined by radioimmunoassay after Sep Pak C18 extraction. Cortisol, T3, T4, FT4 and TSH serum concentrations were measured by enzyme immunoassay. BNP and ANP plasma levels were strongly elevated in patients with renal failure (BNP 22.4 fold, ANP 4.7 fold versus controls [n = 20]) and decreased significantly (p < 0.001) during hemodialysis (BNP [pg/ml]: 192.1 +/- 24.9, 178.6 +/- 23.0, 167.2 +/- 21.8; ANP [pg/ml]: 240.2 +/- 28.7, 166.7 +/- 21.3, 133.0 +/- 15.5). BNP plasma concentrations showed a stronger elevation than ANP plasma levels and a less pronounced decrease during hemodialysis (BNP: 13.5 +/- 1.8%, ANP: 40.2 +/- 3.5%, p < 0.001) which might in part be due to the longer half-life of BNP. Cortisol and TSH levels did not change significantly whereas T3, T4 and FT4 levels increased significantly (p < 0.001) during hemodialysis. Since corticosteroids and thyroid hormones stimulate natriuretic peptide release, these data suggest that the dialysis-induced decrease of ANP and BNP plasma concentrations is not augmented by a loss of cortisol or thyroid hormones during hemodialysis. The present data provide support that BNP and ANP plasma concentrations are sensitive indicators of the extracellular fluid volume status.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Female; Humans; Hydrocortisone; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Renal Dialysis; Thyroid Hormones

The plasma concentration of immunoreactive human brain natriuretic peptide (ir-BNP) was measured in 40 patients on hemodialysis (HD) and in 12 healthy subjects. Immunoreactive human atrial natriuretic peptide (ir-ANP) was also measured. The mean (+/- SE) plasma ir-BNP concentration in the patients before HD (18.4 +/- 3.4 fmol/mL) was markedly higher than that in the control group (0.39 +/- 0.08 fmol/mL). The plasma ir-BNP level was significantly decreased by HD from 18.4 +/- 3.4 fmol/mL to 10.5 +/- 2.2 fmol/mL (P < 0.001), but the latter value was still higher than the upper limit of the normal range for our laboratory. There were significant correlations between the plasma ir-ANP level and the mean blood pressure before HD (P < 0.05) and between the HD-induced changes in plasma ir-ANP level and mean blood pressure (P < 0.001). These correlations were not observed between the plasma ir-BNP level and mean blood pressure. The plasma ir-BNP level correlated with the cardiothoracic ratio and this correlation was closer to that between the plasma ir-ANP level and cardiothoracic ratio. Ultrasound echocardiographic studies in 13 patients revealed that the pre-HD state of high cardiac output was correlated by HD in association with decreases in plasma ir-BNP and ir-ANP levels. Correlations were observed between the pre-HD ir-ANP level and the interventricular septal thickness index (r = 0.68, P < 0.05) and between the change in ir-BNP level and that in left atrial diameter (r = 0.806, P < 0.001). In conclusion, BNP levels were high in HD patients compared with the control subjects and were decreased during HD. In addition, BNP and ANP levels correlated with several parameters of volume change and cardiac status.

Topics: Atrial Natriuretic Factor; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Renal Dialysis

We have previously reported that C-type natriuretic peptide (CNP), the third member of natriuretic family, was produced in vascular endothelial cells and hypothesized that CNP might be a local regulator of vascular tone and/or growth from endothelial cells. In order to clarify the pathophysiological significance of CNP in humans, we examined the presence of CNP in human circulation and determined plasma levels of CNP in patients with various cardiovascular disorders. The plasma level of CNP in healthy persons was 1.4 +/- 0.6 fmol/ml (n = 13). The plasma level of CNP was markedly increased in patients with septic shock (13.2 +/- 10.1 fmol/ml, n = 11), while there was no alteration in patients with congestive heart failure or hypertension. There was two-fold increase of the plasma CNP level in patients with chronic renal failure. These results indicate that CNP, which can be considered as an endothelium-derived relaxing peptide, is detectable in human circulation and suggest the pathophysiological significance of endothelial CNP in humans.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Chromatography, Gel; Chromatography, High Pressure Liquid; Cross Reactions; Heart Failure; Humans; Hypertension; Kidney Failure, Chronic; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Nerve Tissue Proteins; Reference Values; Shock, Septic

The human heart secretes both atrial natriuretic peptide and brain natriuretic peptide. This study attempts to clarify the pathophysiological significance of the peptides in cardiovascular diseases. Using immunoradiometric assay, plasma brain natriuretic peptide and atrial natriuretic peptide levels in essential hypertension, various secondary hypertension, chronic renal failure, chronic heart failure during cardiac pacing, and acute myocardial infarction were determined. Mean plasma brain natriuretic peptide and atrial natriuretic peptide levels in healthy subjects were 3.7 +/- 0.3 and 5.7 +/- 0.3 pmol/L, respectively, and increased as a function of age. Plasma brain natriuretic peptide levels showed a larger increase than atrial natriuretic peptide levels in various cardiovascular diseases. In chronic renal failure, whereas plasma atrial natriuretic peptide levels decreased significantly after hemodialysis and were correlated with the changes in body weight, changes in plasma brain natriuretic peptide levels were less prominent and did not show such a correlation. In chronic heart failure, both basal plasma brain natriuretic peptide and atrial natriuretic peptide levels were also significantly elevated. However, in response to acute ventricular or atrial pacing, brain natriuretic peptide levels did not show any increase in contrast to the marked increase of atrial natriuretic peptide levels. In acute myocardial infarction, brain natriuretic peptide levels showed more prominent changes than atrial natriuretic peptide levels and were correlated with serum levels of creatine kinase and cardiac myosin light chain I in most patients. These results suggest that both brain and atrial natriuretic peptides play an important role in the regulation of cardiovascular homeostasis.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenal Gland Neoplasms; Adult; Aged; Aging; Atrial Natriuretic Factor; Cardiac Pacing, Artificial; Cardiovascular Diseases; Female; Heart Failure; Humans; Hyperaldosteronism; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Pheochromocytoma; Reference Values; Regression Analysis; Renal Dialysis

To evaluate the additive effect of moderate chronic renal failure to the abnormal dopamine generation and action observed in stable hypertension, we investigated 22 age-matched patients with a comparable degree of hypertension with and without chronic renal failure. Both groups were compared with each other and with an age-matched control group after a single oral dose of dihydroxyphenylalanine (DOPA) while cardiorenal responses and DOPA, dopamine, and their metabolites were measured. The hypertensive patients with chronic renal failure shared with their hypertensive counterparts without chronic renal failure an impaired DOPA decarboxylation to dopamine. However, patients with chronic renal failure had decreased hemodynamic and normal natriuretic responses compared with the hypernatriuresis of hypertensive patients with normal renal function; patients with chronic renal failure had elevated basal plasma concentrations of DOPA and dopamine sulfates as well as increased plasma and urinary DOPA sulfate but blunted urinary dopamine sulfate increases after DOPA administration; they presented augmented plasma atrial natriuretic factor concentrations. Thus, hypertensive patients with moderate chronic renal failure exhibit a decreased hemodynamic responsiveness to DOPA administration-induced dopamine elevation but with the natriuretic effect of dopamine maintained (possibly because of its permissive interaction with increased atrial natriuretic factor levels). Hypertensive patients with chronic renal failure have a heightened DOPA and dopamine sulfoconjugating propensity. Dopamine sulfate attenuates the biologic action of free dopamine. This may contribute (possibly via glomerular hypertension and hyperfiltration due to decreased postglomerular vasodilation) to progressive hypertensive renal damage, particularly in groups predisposed to dopamine deficiency, such as diabetics, blacks, and the elderly.

Topics: 3,4-Dihydroxyphenylacetic Acid; Atrial Natriuretic Factor; Blood Pressure; Creatinine; Diastole; Dihydroxyphenylalanine; Dopamine; Female; Homovanillic Acid; Humans; Hypertension; Kidney Failure, Chronic; Levodopa; Male; Middle Aged; Reference Values; Sodium

Two groups of subjects were studied. The group A consisted of 40 patients treated by HD (haemodialysis) (mean age--x +/- SEM 38.6 +/- 1.47 years, duration of haemodialysis treatment 36.8 +/- 3.7 months, cuprophan dialyzers and acetate containing solution--38 mEg/l--were used, time of HD--4 hours 3 times weekly, predialysis serum creatinine was 900.8 +/- 32.1 mumol/l (10.2 +/- 0.4 mg%) postdialysis serum creatinine was 467.8 +/- 28.3 mumol/l (5.3 +/- 0.3 mg%). Patients were not treated with erythropoietin. The control group comprised 20 healthy subjects (mean age 36.7 +/- 2.7 years and serum creatinine level 76.7 +/- 3.5 mumol/l (0.9 +/- 0.1 mg%). In all examined subjects the following experimental protocol was used. In both group blood pressure (BP) and heart rate (HR) were determined at about 8 a.m. after an overnight rest. Then blood samples were withdrawn for estimation of ANP, endothelin, haematocrit value (Ht), haemoglobin (Hb) and creatinine concentrations. Between 8 and 12 a.m. all examined subjects of the group A were dialysed. After each hour of dialysis BP and HR were measured and blood samples were withdrawn ANP (Peninsula Lab.Kids.) and endothelin (Amersham Kids) were measured using RIA methods, but other biochemical parameters using routine methods. Serum creatinine and plasma ANP levels significantly decreased after HD. Plasma endothelin level was significantly higher than in the control subjects. After first hour of HD a significant decrease of plasma endothelin was observed and than plasma endothelin level started to increase. No significant correalations between creatinine, ANP and endothelin levels in examined group was observed.

Topics: Adult; Atrial Natriuretic Factor; Creatinine; Endothelins; Humans; Kidney Failure, Chronic; Renal Dialysis

We investigated the effect of volume overload on the plasma concentrations of brain and atrial natriuretic peptides as well as cyclic GMP, using specific radioimmunoassays, in 49 patients with chronic renal failure on regular hemodialysis treatment. Markedly elevated levels of the brain (16.2 +/- 1.3 pmol/l) as well as atrial (39.0 +/- 2.8 pmol/l) natriuretic peptide in plasma were found before the dialysis session, as compared to healthy volunteers (range for brain natriuretic peptide, 0.7-7.3 pmol/l, mean level 2.55 +/- 0.32 (SEM) pmol/l). In contrast to the levels of the atrial natriuretic peptide, those of the brain natriuretic peptide were lowered less efficiently by the dialysis procedure: The mean pre-/postdialytic concentration differences were -1.5 pmol/l and -14.2 pmol/l for brain and atrial natriuretic peptide, respectively. The concentrations of the intracellular mediator of the natriuretic peptides, cyclic GMP, were found to be excessively elevated (34.8 +/- 2.8 nmol/l) and returned to near-normal values (12.4 +/- 1.6 nmol/l) at the end of the dialysis session. Concentrations of BNP in plasma of the patients were well correlated to those of ANP. Significant though less marked correlations were also observed between the plasma concentrations of cyclic GMP and BNP, or ANP, respectively. In contrast to those of ANP, pre-/postdialysis differences in plasma BNP concentrations were not correlated to the extent of volume reduction during dialysis. Our findings show that pathophysiologic states resulting in elevations of the plasma concentrations of the atrial natriuretic peptide can also lead to increased levels of the brain natriuretic peptide.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Cyclic GMP; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Renal Dialysis

The major stimulus for atrial natriuretic peptide (ANP) release is atrial stretch and increased values are observed in volume overload states such as chronic renal failure. Since successful kidney transplantation restores volume homeostasis, we compared the effects of human cadaveric kidney transplantation on time course and changes of plasma ANP in the early postoperative period in 4 patients with successful and 4 patients with failed transplantation. ANP concentrations were elevated before transplantation in both groups (91 +/- 16 and 70 +/- 32 pmol/l) and decreased after successful (50 +/- 27 pmol/l, day 16) but increased after failed transplantation (146 +/- 45 pmol/l, day 16). Moreover, there was a close correlation between changes of body weight and ANP concentrations. Plasma renin activity decreased and plasma noradrenaline increased non-significantly in both groups, the latter more so after failed transplantation (116 +/- 42 to 194 +/- 156 vs 156 +/- 157 to 425 +/- 287 ng/l). No correlation was found between changes of renin activity or plasma catecholamines and ANP concentrations. The results indicate that the mechanisms governing release of atrial natriuretic peptide are operative in patients with chronic end-stage renal failure and after successful kidney transplantation with a return of atrial natriuretic peptide concentrations towards normal in the latter.

Topics: Adult; Aged; Atrial Natriuretic Factor; Body Weight; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Norepinephrine; Renin

The changes in blood volume (BV), atrial natriuretic peptide (ANP), plasma renin activity (PRA), aldosterone (Aldo), norepinephrine (NE), epinephrine (Epi), parathyroid hormone (PTH), arginine vasopressin (AVP) and the cyclic nucleotides cAMP and cGMP were measured during a fluctuating BV cycle in 15 patients with end-stage renal failure maintained on chronic hemodialysis (HD). HD consisted of 4 periods of about 60 min each. The first half of each HD period consisted of ultrafiltration (UF) greater than 1,000 ml/h, and the second half consisted of no UF. Changes in relative BV were measured using continuous hemoglobinometry. Total BV at the end of treatment was 74.3 +/- 6.9% of the pretreatment volume. A significant positive correlation between BV and the levels of ANP, PTH, Epi and cGMP and an inverse correlation between BV and PRA, Aldo, AVP and NE were demonstrated. While mean values of NE and AVP levels were directly related to actual changes in BV, individual values did not homogeneously reflect this relationship. The cyclic nucleotides cGMP and cAMP did not follow immediate BV changes, but showed a significant decrease correlated with diminished BV. Based on a pre-postdialysis analysis, significant changes in PRA and Aldo were missing. It seems possible that vascular stability in dialysis patients may be maintained by the response of NE and AVP, and not by the renin-aldosterone system. The changes in ANP and cGMP values correlated most significantly (r = 0.38 and r = 0.51, p < 0.005) with the changes in BV, but no single variable could explain the blood pressure regulation during HD with intermittent rapid UF.

Topics: Adult; Aged; Aldosterone; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Blood Volume; Cyclic AMP; Cyclic GMP; Epinephrine; Heart Rate; Hemodiafiltration; Humans; Kidney Failure, Chronic; Male; Middle Aged; Norepinephrine; Parathyroid Hormone; Renal Dialysis; Renin; Time Factors; Vasoconstrictor Agents

Vena cava diameter (VCD) was measured by ultrasonography in 10 acutely hypervolemic dialysis patients (6 men, 4 women; mean age 61.3 +/- 15.4 years), results being compared with the level of the central venous pressure (CVP) and, in 39 long-term dialysis patients (18 men, 21 women; mean age 56 +/- 15 years), with the plasma concentration of atrial natriuretic peptide (ANP). In 86 subjects without renal disease (43 men, 43 women; mean age 39.4 +/- 14.6 years) there was a statistically highly significant correlation between the end-expiratory VCD and heart rate (r = -0.63; P < 0.001). These data were used to construct a VCD/heart rate (HR) nomogram. In the ten dialysis patients HR-adjusted VCD correlated significantly at various hydration states (54 measurements) with the CVP (r = 0.72; P < 0.001). The steep slope for the relationship between CVP and VCD showed marked interindividual variations. However, in all patients (except one) with a raised CVP (> 12 cm H2O) the HR-adjusted VCD was above the 95th percentile. In the 39 patients on long-term dialysis (13 with, 25 without predialysis tricuspid regurgitation [TR] there occurred a parallel decrease in VCP and ANP during removal of fluid. In the 25 patients without TR, the fall in ANP concentration and VCD correlated significantly (r = 0.70; P < 0.001). These results indicate that, in patients with renal failure but normal cardiac function, measurement of the VCD by ultrasonography provides an adequate index of hydration.

Topics: Adult; Aged; Atrial Natriuretic Factor; Central Venous Pressure; Echocardiography; Female; Heart Rate; Humans; Kidney Failure, Chronic; Male; Middle Aged; Plasma Volume; Renal Dialysis; Venae Cavae

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Circadian Rhythm; Female; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged

Hypotension is a frequent complication in patients subjected to regular hemodialysis. Insufficient regulation of blood pressure following dialysis with ultrafiltration has been attributed to a lack in hormone activation. To determine whether altered production of vasoactive hormones is involved in the breakdown of blood pressure regulation during hemodialysis (HD), blood volume (BV), atrial natriuretic peptide (ANP), plasma renin activity (PRA), aldosterone (Aldo), norepinephrine (NE), epinephrine (Epi), intact immunoreactive parathyroid hormone (iPTH) and arginine vasopressin (AVP) were examined. The relative BV was measured by continuous hemoglobinometry during the HD period of about 240 min. The total decrease in BV at the end of treatment was 23.5 +/- 4.8% of the pretreatment value. Systolic blood pressure (SBP) was 99.6 +/- 23.0 mmHg before dialysis compared with 74.6 +/- 18.8 mmHg at the end of dialysis and heart rate (HR) increased from 76.3 +/- 5.5/min before to 92.0 +/- 10.0/min at the end of dialysis. Despite the wide range of interindividual variance, the hormonal changes indicate that hypotensive patients under HD develop reduced sensitivity of the angiotensin-renin, adrenergic and AVP systems to volumetric stimuli. A paradoxical activation in iPTH and PRA independent Aldo secretions is apparent.

Topics: Aldosterone; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Blood Volume; Epinephrine; Female; Heart Rate; Hormones; Humans; Hypotension; Kidney Failure, Chronic; Male; Middle Aged; Norepinephrine; Parathyroid Hormone; Renal Dialysis; Renin

In 13 patients with chronic renal failure on maintenance hemodialysis, plasma vasopressin, atrial natriuretic factor, catecholamines and renin activity were measured during ordinary hemodialysis with fluid removal, and during isolated isoosmotic ultrafiltration and a subsequent isovolemic hemodialysis. Concomitant with a significant fall in serum osmolality, plasma vasopressin decreased significantly from 6.3 +/- 0.8 to 3.8 +/- 0.4 pg/ml (p < 0.05). Predialytic plasma vasopressin was significantly correlated to serum osmolality (r = 0.62, p = 0.001). No such relationship was observed after dialysis. During isolated ultrafiltration (1.25 +/- 0.13 L) through 1 hour, no change in either osmolality or vasopressin was observed, whereas atrial natriuretic factor decreased (700 +/- 136 to 564 +/- 115 pg/ml, p < 0.05). Atrial natriuretic factor was excessively high at all times, and may explain the low plasma renin activity observed in these patients even after fluid removal. No consistent changes were observed in the catecholamines during hemodialysis or ultrafiltration alone, despite marked changes in blood pressure and heart rate. Thus, even in patients with chronic renal failure osmotic regulation of vasopressin seems intact, and volume reduction through ultrafiltration causes a decrease in atrial natriuretic factor.

Topics: Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Catecholamines; Female; Hemofiltration; Humans; Kidney Failure, Chronic; Kidney Function Tests; Male; Middle Aged; Renal Dialysis; Renin; Water-Electrolyte Balance

To examine whether atrial natriuretic factor (ANF) is secreted adequately in the early phase of myocardial infarction, plasma ANF concentration and clinical parameters, including hemodynamic variables, were studied in 118 patients with acute myocardial infarction (AMI). The patients were divided into 2 subgroups according to the absence (group A, n = 41) or presence (group B, n = 77) of a history of valvular heart disease, previous myocardial infarction, hypertension, or renal failure. Although no significant difference in atrial pressure after the infarction was found between the 2 groups, the plasma ANF level was significantly lower in group A than in group B (76 +/- 6 vs. 185 +/- 26 pg/ml; mean +/- SEM, p < 0.01). Plasma ANF was correlated with pulmonary capillary wedge pressure in group B (r = 0.54, p < 0.001), whereas no relationship with hemodynamic parameters was observed in group A. In 56 of the 118 patients (group A, n = 18; group B, n = 38), the pulmonary arterial plasma level was significantly higher in group A (p < 0.05), whereas the difference was not significant in group B. Seven of the 8 expired cases among these 56 patients had peripheral plasma ANF levels of more than 150 pg/ml, which were higher than those in pulmonary arterial plasma. These observations suggest firstly that the plasma level of ANF is lower in patients with a new onset of myocardial infarction compared to those with a history of cardiac or renal diseases, and secondly that stimulated ANF release originates not only from the right side of the heart, but also from additional site(s), particularly in patients with chronic ventricle overload and a poor prognosis.

Topics: Atrial Function, Right; Atrial Natriuretic Factor; Female; Heart Valve Diseases; Hemodynamics; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Myocardial Infarction; Pulmonary Wedge Pressure; Risk Factors

The radioimmunologic assays appeared to be the most convenient methods for determination of atrial natriuretic peptide (ANP) concentration in blood plasma. The purpose of this work was to compare the control quality parameters of two radioimmunologic methods for the ANP determination in human plasma: the methods described by Pruszczyński et al. and the method with the use of Amersham ready-made set (kit). The comparison of the two methods was performed by analyzing 10 series of ANP determinations carried out by Pruszczyński method, and 15 series by means of the kit. Both methods appeared to fulfil the criteria of satisfactory quality for RIA determinations. The second purpose of this study was to define the utility of the RIA method for the determination of ANP in clinical practice, taking into the consideration some factors influencing or modifying plasma ANP levels. Three groups of persons of were studied: 15 healthy subjects, 16 patients with acromegaly and 47 patients with the impairment of renal function. The ANP level in plasma was determined in these 3 groups of persons. It has been demonstrated that the change of body position from upright to supine caused the increase of the ANP concentration in plasma. It has also been found that the decrease in the intravascular fluid volume induced by furosemide administration resulted in the reduction of ANP concentration in plasma. The enlarged intravascular fluid volume, accompanying acromegaly and probably present in persons with the impairment of kidneys, was associated with the increased ANP concentrations in plasma.

Topics: Acromegaly; Adult; Atrial Natriuretic Factor; Blood Pressure; Diagnostic Errors; Female; Furosemide; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Poland; Posture; Quality Control; Radioimmunoassay; Reagent Kits, Diagnostic

Chronic renal failure was induced in male Wistar rats with 5/6 nephrectomy (group I) and sham-operation was carried in the controls (group II). The results showed that in group I, plasma ANP levels increased progressively as Scr elevated. The plasma levels of renin and angiotensin raised simultaneously as compared with the controls (P < 0.001). At the 20th week after operation, urine volume and Na decreased significantly (P < 0.05) and the number of glomerular ANP receptors decreased significantly at the 12th week (P < 0.05) and 20th week (P < 0.01). Our data suggest that in 5/6 nephrectomized rats: 1. The elevation of plasma ANP level might be partly caused by damage of glomerular receptors. 2. The elevated plasma ANP could not cause its diuretic, natriuretic, blood pressure depression and R-A inhibition effect due to the damage of kidney ANP receptors.

Topics: Aldosterone; Angiotensin II; Animals; Atrial Natriuretic Factor; Kidney; Kidney Failure, Chronic; Male; Nephrectomy; Rats; Rats, Wistar; Receptors, Atrial Natriuretic Factor

Plasma atrial natriuretic peptide (ANP) and cyclic 3'5'-guanosine monophosphate (cGMP) were investigated as indicators of fluid volume overload in children and adolescents with chronic renal failure. Plasma ANP and cGMP were measured in both paediatric patients with chronic renal failure (n = 17, mean serum creatinine 371 +/- 242 mumol/l) and those with end-stage renal disease on haemodialysis (n = 18). cGMP was higher in children with chronic renal failure than in 45 healthy controls (1.0 +/- 0.4 vs 2.1 +/- 0.8 nmol/l, P less than 0.01), whereas plasma ANP was similar (26.9 +/- 9.7 vs 34.0 +/- 12.3 pmol/l). Both ANP and cGMP were markedly elevated in children with end-stage renal disease before haemodialysis and fell significantly during dialysis. During dialysis body weight decreased by 1.6 +/- 0.7 kg, corresponding to 4.5 +/- 2.1% of body weight. Plasma ANP correlated positively with plasma cGMP in haemodialysed patients (r = 0.43, P less than 0.05). Reduction in body weight and in mean arterial pressure correlated more closely with plasma ANP than with cGMP. Therefore, elevation of plasma ANP appears to indicate volume overload in children undergoing haemodialysis, but whether it can be used also in children with chronic renal failure requires further investigation.

Topics: Adolescent; Adult; Atrial Natriuretic Factor; Blood Volume; Body Weight; Child; Child, Preschool; Creatinine; Cyclic GMP; Female; Humans; Kidney Failure, Chronic; Male; Renal Dialysis; Water-Electrolyte Imbalance

Topics: Atrial Natriuretic Factor; Humans; Kidney Failure, Chronic; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface; Renal Dialysis; Vasodilation

The postdialytic plasma level of cGMP, a marker for the release of atrial natriuretic peptide (ANP) in humans, is closely related to hypervolemia in chronic hemodialysis patients. In order to test the practicability of routine postdialysis cGMP determination for the detection of fluid overload, ANP and cGMP levels in the total hemodialysis population of 81 patients were measured with blood samples drawn immediately after hemodialysis. Twenty-three patients had a cGMP level of more than 20 pmol/mL. In 13 of these, pulmonary congestion was present on the chest roentgenogram. Two of these patients refused a gradual reduction of their dry body weight. In the remaining 21 patients, the weight reduction was associated with a decrease in cGMP levels in all cases and with a decrease in ANP levels in all but two cases. Fourteen of the 21 patients reached a cGMP level below 20 pmol/mL after weight reduction, and at that time, none of these showed signs of pulmonary congestion on chest x-ray. All seven patients, whose cGMP levels remained above 20 pmol/mL despite the reduction, had documented heart disease with impairment of left ventricular function. These results suggest that the plasma cGMP level after hemodialysis is more apt for the determination of dry body weight than is ANP or a chest roentgenogram.

Topics: Adult; Aged; Antihypertensive Agents; Atrial Natriuretic Factor; Biomarkers; Body Weight; Cardiovascular Diseases; Cyclic GMP; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Nitric Oxide; Predictive Value of Tests; Pulmonary Edema; Radiography; Renal Dialysis; Ventricular Function, Left; Water-Electrolyte Imbalance

1. We have developed a radioimmunoassay for the measurement of immunoreactive brain natriuretic peptide (1-32) in human plasma. Simultaneous measurements of atrial natriuretic peptide have also been carried out to allow for direct comparison between circulating brain natriuretic peptide and atrial natriuretic peptide. Plasma levels of immunoreactive brain natriuretic peptide (means +/- SEM) were 1.1 +/- 0.1 pmol/l in 36 normal healthy subjects and were significantly elevated in cardiac transplant recipients (18.8 +/- 3.9 pmol/l, n = 12) and in patients with dialysis-independent (8.8 +/- 1.5 pmol/l, n = 11) or dialysis-dependent (41.6 +/- 8.8 pmol/l, n = 14) chronic renal failure. Similarly, in these groups of patients plasma levels of atrial natriuretic peptide were also significantly raised when compared with those in the group of normal healthy subjects. 2. The plasma level of atrial natriuretic peptide was significantly higher than that of brain natriuretic peptide in normal subjects and in patients with dialysis-independent chronic renal failure, with ratios (atrial natriuretic peptide/brain natriuretic peptide) of 2.8 +/- 0.2 and 2.2 +/- 0.3, respectively. However, in both cardiac transplant recipients and patients on dialysis plasma levels of atrial natriuretic peptide and brain natriuretic peptide were similar, with ratios of 1.3 +/- 0.2 and 1.0 +/- 0.1, respectively, in these two groups. 3. Plasma levels of brain natriuretic peptide and atrial natriuretic peptide were significantly correlated in the healthy subjects and within each group of patients. When all groups were taken together, there was an overall correlation of 0.90 (P < 0.001, n = 73).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Atrial Natriuretic Factor; Female; Heart Transplantation; Humans; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Renal Dialysis

The fasting plasma levels of 10 vasoactive regulatory peptides were measured by radioimmunoassay in 23 stable patients with chronic renal failure receiving regular hemodialysis treatment (RDT) and compared with those of healthy controls. The plasma concentrations of arginine vasopressin, atrial natriuretic peptide, beta-endorphin, methionine-enkephalin, motilin, neuropeptide Y, substance P, and vasoactive intestinal peptide were increased. The plasma level of calcitonin gene-related peptide was not statistically different from that of the controls. The plasma concentration of gamma 2-melanocyte-stimulating hormone was lowered in the RDT-patients. The arterial blood pressure correlated with the plasma levels of motilin and neuropeptide Y. We conclude that patients with chronic renal failure receiving RDT have increased concentrations of 8 out of 10 measured vasoactive regulatory peptides. The elevated levels of vasoactive peptides may contribute to the adaptation of the cardiovascular system to impaired renal function.

Topics: Adult; Aged; Aged, 80 and over; Arginine Vasopressin; Atrial Natriuretic Factor; beta-Endorphin; Blood Pressure; Enkephalin, Methionine; Female; Humans; Kidney Failure, Chronic; Kidney Function Tests; Male; Middle Aged; Motilin; Neuropeptide Y; Neuropeptides; Renal Dialysis; Substance P; Vascular Resistance; Vasoactive Intestinal Peptide

Studies were done in partially nephrectomized rats to examine the effect of dietary sodium intake on atrial natriuretic factor (ANF) released by the atria. Experiments were done in four groups of male Wistar rats. Group 1 (n = 10) and 3 (m = 10) rats were sham-operated. Group 2 and 4 were 5/6 nephrectomized. Group 1 and 2 were fed a sodium-supplemented diet. Group 3 and 4 received a sodium-deficient diet. Renal functions were similar between group 2 and 4. Plasma ANF level was raised in group 2 (182 +/- 17 pg/ml). Circulating ANF levels in group 1,3 and 4 were 95 +/- 5, 90 +/- 5 and 95 +/- 4 pg/ml, respectively. Atrial ANF contents were higher in partially nephrectomized rats after receiving a sodium-supplemented diet. A reduction in atrial ANF contents occurred when fed a sodium-deficient diet. In vitro studies were done to assess the rate of ANF released. ANF secretory rates were highest in group 2 (11 +/- 1.5 pg/min/mg). There was no difference between group 1,3 and 4. A positive correlation was found between plasma ANF and ANF released in all groups examined. Thus, plasma ANF levels were a good reflection of ANF secretory rates. A significant correlation existed between plasma ANF and sodium excretion in chronic renal failure rats (r = 0.78; p less than 0.01). A dissociation between plasma ANF and water excretion was seen. These results suggest that in chronic renal failure rats, ANF played a role in sodium adaptation.

Topics: Adaptation, Physiological; Animals; Atrial Natriuretic Factor; Kidney Failure, Chronic; Male; Natriuresis; Nephrectomy; Rats; Rats, Inbred Strains; Sodium, Dietary

The immunoreactivity of plasma and urine atrial natriuretic peptide (ANP) was measured in patients with renal disease and in healthy volunteers. The molecular forms of ANP in these subjects were estimated by gel permeation chromatography and reverse phase high performance liquid chromatography. No significant increase in plasma ANP was observed in patients with nephrotic syndrome or non-oliguric chronic renal failure compared to healthy volunteers. However, plasma ANP levels were significantly increased in patients on hemodialysis (normal 18.6 +/- 11.4 fmol/ml; hemodialysis 91.2 +/- 69.9 fmol/ml, p < 0.01). Chromatographic analyses revealed that plasma ANP consisted of only alpha-ANP or combined alpha- and gamma-ANP in healthy volunteers and in nephrotic patients, whereas beta-ANP frequently appeared in the plasma of both dialyzed and non-dialyzed chronic renal failure patients. Excreted forms, except in subjects free from renal disease where gamma-ANP may serve as a potential marker of glomerular injury in humans.

Topics: Adult; Atrial Natriuretic Factor; Chromatography, Gel; Chromatography, High Pressure Liquid; Female; Humans; Kidney Diseases; Kidney Failure, Chronic; Male; Middle Aged; Nephrotic Syndrome; Peptide Fragments; Radioimmunoassay; Renal Dialysis

Topics: Aldosterone; Atrial Natriuretic Factor; Diuretics; Humans; Kidney; Kidney Failure, Chronic; Kidney Function Tests; Prostaglandins; Renin; Sulfonamides; Vasodilation

Diurnal change of plasma atrial natriuretic peptide (ANP) concentration was investigated in 12 patients with hypertension due to chronic renal failure (CRF) and in 12 patients with essential hypertension (EH) of comparable degree. Blood pressure (BP) monitoring was performed at 15-min intervals, while peripheral blood samples were obtained at 4-hour intervals starting from 8.00 h. The mean 24-hour plasma levels (+/- SEM) of ANP were 24.3 +/- 1.8 pmol/l in EH and 23.4 +/- 1.2 pmol/l in CRF. In EH, plasma ANP concentration was highest at 4.00 h (33.5 +/- 0.8 pmol/l) and lowest at 16.00 h (15.5 +/- 0.6 pmol/l). In CRF, no significant circadian change was present (22.2 +/- 3.1 and 20.4 +/- 3.6 pmol/l, respectively), and the nocturnal fall in BP was lost. Our data demonstrate that in CRF the loss and possible reversal of the nocturnal decline in BP is associated with the disappearance of any significant circadian variation in the circulating concentrations of ANP. These findings suggest a role for ANP in the alteration of BP variability of CRF, possibly mediated by autonomic dysfunction, and are further evidence for the existence of a relation between the circadian rhythms of ANP and BP.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Circadian Rhythm; Female; Glomerulonephritis; Heart Rate; Humans; Hypertension, Renal; Kidney Failure, Chronic; Male; Middle Aged; Pyelonephritis

The role of the rate of increase in hematocrit (Hct) and changes in vasoactive substances as a cause of hypertension induced by the administration of recombinant erythropoietin (r-EPO) were examined in 20 stable hemodialysis (HD) patients. Measurements were made twice at the start of treatment and when the Hct reached 30%. Patients were divided into 2 groups: Group I: 14 patients received r-EPO, 3000 units intravenously three times a week. Group II: 6 patients, needing repeated blood transfusion, were given 2 to 4 units of washed red blood cells during a HD session. The Hct increased by 0.65%/week in Group I and by 6.7%/2 days in Group II. An elevation in blood pressure was not seen in any patient. There was no difference in the levels of renin, angiotensin II, epinephrine, norepinephrine, dopamine, atrial natiuretic peptide (ANP), BUN, creatinine, cardiac thoracic ratio and body weight in any of the groups. In conclusion, elevation of the Hct in HD patients whatever the rate of increase within the 30% Hct range, does not cause an increase in blood pressure. In addition, the levels of vasoactive substances do not change in partially corrected anemic HD patients. As a result blood pressure control can be helped by aiming at the lower target Hct level of around 30%.

Topics: Angiotensin II; Atrial Natriuretic Factor; Blood Pressure; Blood Transfusion; Catecholamines; Dopamine; Epinephrine; Erythropoietin; Female; Hematocrit; Humans; Hypertension; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Norepinephrine; Pilot Projects; Recombinant Proteins; Renal Dialysis; Renin

Human atrial natriuretic peptide (HANP) is a hormone with the physiological characteristics of a regulator of body fluid volume. We studied whether, or not, it is possible to use HANP as a parameter to determine the so-called dry weight (D.W.) in patients on maintenance dialysis. Subjects for experiments included 117 hemodialysis (HD) patients, 18 chronic renal failure (CRF) patients under conservative treatment and 20 normal controls. Plasma HANP level was much higher in HD patients than in controls. In CRF patients treated conservatively, there was no significant correlation between plasma HANP and the degree of renal dysfunction. In HD patients plasma HANP showed a significant positive correlation with CTR (r = 0.408, p less than 0.001), but no correlation with the age or duration of hemodialysis. During hemodialysis, the plasma HANP level fell with the lapse of time significantly (p less than 0.001). In HD patients without complications, plasma HANP level after HD were significantly higher (p less than 0.001) in ones with CTR of 50% or more than with CTR of less than 50%. Plasma HANP may play an important part in regulating the balance of body fluid volume. These findings suggest that plasma HANP is useful as a parameter to determine the D.W. in patients on hemodialysis.

Topics: Adolescent; Adult; Aged; Atrial Natriuretic Factor; Body Fluids; Body Weight; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

We examined the effects of 60 min alpha-hANP infusion (24 ng/min/kg) on glomerular filtration rate (GFR), renal blood flow (RBF), cardiac index (CI) and blood pressure (BP) in 8 patients with chronic renal failure (CRF) with GFR ranging from 18 to 80 ml/min/1.73 m2 and in 8 control (C) subjects with normal renal function. Basal plasma levels of ANP and cGMP were elevated in CRF (ANP: 60.6 +/- 9.1 vs 13.6 +/- 1.9 pmol/l, p less than 0.05; cGMP: 14.3 +/- 2.9 vs 6.6 +/- 1.1 pmol/ml, p less than 0.05). During ANP infusion, peak levels of cGMP were higher in CRF than in C (27.5 +/- 3.2 vs. 17.3 +/- 1.3 pmol/ml, p less than 0.05). During ANP infusion, GFR increased in CRF by 70.7 +/- 4.2% from 34.5 +/- 6.8 to 57.4 +/- 9.9 ml/min/1.73 m2 (p less than 0.001) as compared to 16.2 +/- 1.4% in C (p less than 0.001 vs CRF). RBF increased in CRF by 43.6 +/- 6.4% and in C by 3.1 +/- 1.2% (p less than 0.01). Basal urinary sodium excretion (UNaV) was slightly lower in CRF than in C but rose to the same level in both groups during ANP infusion. In CRF, as opposed to C, UNaV remained elevated above baseline after the end of the infusion. The effect of ANP on fractional sodium excretion (FENa), however, was more pronounced in C.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Atrial Natriuretic Factor; Cyclic GMP; Female; Glomerular Filtration Rate; Hemodynamics; Humans; Kidney Failure, Chronic; Kidney Function Tests; Male; Middle Aged; Renal Circulation; Renin-Angiotensin System; Vascular Resistance; Water-Electrolyte Balance

Topics: Adrenergic beta-Antagonists; Atrial Natriuretic Factor; Blood Pressure; Blood Volume; Echocardiography; Female; Humans; Hypertension, Renal; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Renin

Atrial natriuretic peptide (ANP) and plasma renin activity (PRA) were studied in 19 patients with end-stage renal disease (ESRD) under haemodialysis (HD). On the basis of clinical findings, patients were divided into three groups: group A, 6 patients, of mean age 41 +/- 15 years, without heart failure and in need of ultrafiltration (658 +/- 282 ml h-1); group B, 6 patients, of mean age 54 +/- 15 years, without heart failure under isovolaemic HD; group C, 7 patients, of mean age 60 +/- 3 years, with heart failure (NYHA III-IV) and in need of ultrafiltration (607 +/- 120 ml h-1). The highest predialysis ANP levels were found in group C (1534 +/- 471 pg ml-1) followed by group A (476 +/- 168 pg ml-1) and group B (236 +/- 138 pg ml-1) (normal range 62 +/- 27 pg ml-1). Systolic and diastolic blood pressure and heart rate did not correlate with ANP levels in either of the groups. However, iso-osmotic reduction of the body weight by ultrafiltration was correlated with decreasing ANP levels during HD (for groups A and C, r = 0.88 and 0.98, respectively). Isovolaemic HD did not alter ANP concentrations (group B). All patients received a volume bolus at the end of HD, and they responded with an instant increase in ANP concentration, which was most pronounced in patients with concomitant heart failure. PRA was not significantly correlated with ANP levels during HD. In conclusion, the results of this study indicate that there is a sensitive response of ANP levels to changes in body fluid status in ESRD.

Topics: Adult; Aged; Atrial Natriuretic Factor; Body Weight; Diuresis; Female; Heart Failure; Homeostasis; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Renin; Statistics as Topic; Time Factors; Water-Electrolyte Balance

Indirect evidence suggests that atrial natriuretic peptide (ANP) secretion is augmented in chronic renal disease. The object of our present study is to examine the release of ANP from isolated atria obtained from chronic renal failure rats to directly determine whether ANP secretions are increased under these conditions. Experiments were conducted on male Wistar rats (200-225 g) who were subjected to 5/6 nephrectomy of sham operation. Plasma blood urea nitrogen was significantly elevated in 5/6 nephrectomized rats (65 +/- 7 vs. 16 +/- 1 mg%). Overall glomerular filtration rate was 2.36 +/- 0.06 ml/min in sham-operated animals, as opposed to 0.55 +/- 0.11 ml/min in 5/6 nephrectomized rats. Fractional excretion of sodium was significantly higher in 5/6 nephrectomized rats (0.52 +/- 0.01 vs. 1.68 +/- 0.21%). Plasma ANP was 102 +/- 4 pg/ml in normal rats and 161 +/- 14 pg/ml in 5/6 nephrectomized ones. We have also measured immunoreactive ANP in the atria of normal and 5/6 nephrectomized rats. ANP content and concentration in the atria were lower in 5/6 nephrectomized rats. (652 +/- 34 vs. 515 +/- 46 ng/mg of tissue). Right atria from normal and nephrectomized animals was superfused with a modified Langendorff preparation. Spontaneous release of ANP was significantly higher from the nephrectomized rats (17.5 +/- 0.6 pg/min/mg) than from the normal rats (9.8 +/- 0.3 pg/min/mg). These results suggest that ANP may play a role in sodium homeostasis in rats with reduced renal mass.

Topics: Animals; Atrial Function; Atrial Natriuretic Factor; Blood Urea Nitrogen; Glomerular Filtration Rate; Heart Atria; Hemostasis; Kidney Failure, Chronic; Male; Nephrectomy; Rats; Rats, Inbred Strains; Sodium

Plasma concentrations of immunoreactive alpha ANF were measured before, during, and after 3 hours of hemodialysis (HD) and hemofiltration (HF). In seven healthy subjects plasma alpha ANF concentrations were measured to serve as controls. Highly elevated pre-treatment alpha ANF levels were obtained in the HD group (286 +/- 52 pg/ml, mean +/- SE), and in the HF group (275 +/- 48 pg/ml) as compared with the controls (40 +/- 3 pg/ml). The effect of both HD and HF on the alpha ANF concentration was not significant after the first hour of treatment. However, a significant decrease was obtained after the second (HD = 244 +/- 49, HF = 140 +/- 17) and third hours (HD = 244 +/- 48, HF = 135 +/- 15) (p less than 0.05) in both treatments. A steeper decline in the alpha ANF concentration was notable during HF compared with HD. There was a significant difference (p less than 0.05) when both modalities were compared at the end of treatment. A correlation (r2 = 0.98, p less than 0.001) was noted between changes in the alpha ANF levels and the ultrafiltration (UF) volumes only during HF. Plasma alpha ANF concentrations at the filter outlet were lower than at the inlet in both groups. It is concluded that the plasma alpha ANF concentrations are highly elevated in chronic renal failure patients. Despite the decrease in these concentrations during HD and HF it did not reach the normal plasma level. Monitoring of plasma alpha ANF may be a useful indicator for the extracellular volume status during HD and HF treatments.

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Female; Hemofiltration; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

Atrial natriuretic peptide has been considered to be a major regulator in the body's water and salt homeostasis. Antagonizing those mechanisms leading to volume retention and overload (renin, angiotensin, aldosterone), ANP has been suggested to play a critical role in the pathology of certain diseases like renal failure, congestive heart failure or hypertension. In this regard, we measured ANP plasma concentration in normal healthy dogs and dogs with renal failure, congestive heart failure and Cushing syndrome. ANP levels were slightly decreased in dogs with Cushing disease (n = 9; 5.5 +/- 2 fmol/ml), increased in renal failure (n = 7; 16.2 +/- 5.8 fmol/ml, p less than 0.05) and markedly augmented in dogs with congestive heart failure (n = 14; 52.9 +/- 29.75 fmol/ml, p less than 0.01) as compared to healthy dogs (n = 6; 8.3 +/- 3.5 fmol/ml). Furthermore, characterization of the measured immunoreactivity (IR-ANP) revealed, that up to 50% of the IR-ANP in dogs with congestive heart failure corresponds to the ANP precursor molecule, not found in healthy subjects. This fact might present one possible explanation for the attenuated response to ANP in congestive heart failure. In addition, this finding may also serve a diagnostical purpose.

Topics: Animals; Atrial Natriuretic Factor; Chromatography, High Pressure Liquid; Cushing Syndrome; Dog Diseases; Dogs; Female; Heart Failure; Kidney Failure, Chronic; Male

Plasma concentrations of the immunoreactive N-terminus, C-terminus and 4,000-dalton midportion of the N-terminus of the atrial natriuretic factor (ANF) prohormone were measured before and after hemodialysis in 13 patients with end-stage renal disease. There was a significant (p less than 0.001) fall in the mean plasma concentration of the C-terminus (i.e. ANF, amino acids 99-126 of the prohormone) from 123 +/- 25 to 80 +/- 22 fmol/ml (mean +/- SEM) with dialysis. The whole N-terminus, on the other hand, increased from 9,336 +/- 2,011 to 11,021 +/- 2,134 fmol/ml after dialysis (p less than 0.002). Pro ANF 31-67 (i.e. amino acids 31-67 of the prohormone) increased postdialysis from 27,775 +/- 4,300 to 31,040 +/- 4,840 fmol/ml (p less than 0.003). Only 1.5% of pro ANF 1-98 and pro ANF 31-67 were cleared by the dialyzer membrane while 15% of ANF crossed the membrane. Thus, with hemodialysis the C-terminus decreases while the N-terminus and pro ANF 31-67 from the midportion of the N-terminus of the ANF prohormone increase in plasma which is partially explained by their respective abilities to cross the dialyzer membrane.

Topics: Aged; Atrial Natriuretic Factor; Humans; Kidney Failure, Chronic; Middle Aged; Molecular Weight; Peptide Fragments; Protein Precursors; Radioimmunoassay; Renal Dialysis

Atrial natriuretic peptide (ANP), a recently discovered cardiac hormone, is an important regulator of body fluid homeostasis. Twenty patients with established chronic renal failure and on maintenance haemodialysis were studied before and after dialysis with capillary dialysers. ANP was determined by RIA after extraction. Mean (+/- SD) pre-dialysis ANP concentration was 146 +/- 51 pg/ml and decreased significantly during dialysis to 68 +/- 38 pg/ml (p less than 0.001). Per cent and absolute changes in plasma ANP level correlated significantly with concomitant changes in body weight (r = 0.764; p less than 0.001 and r = 0.558; p less than 0.01, resp.) but not with changes in serum creatinine, blood pressure or serum electrolytes. The obtained results indicate that ANP levels in patients with chronic renal failure are elevated mainly due to fluid overload, and the rapid fall in ANP concentration observed during haemodialysis is caused by the removal of excess fluid from the body.

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Creatinine; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Potassium; Renal Dialysis; Sodium; Time Factors

Plasma concentrations of human atrial natriuretic peptide (99-126) are elevated in patients with end-stage chronic renal failure and on haemodialysis. Plasma atrial natriuretic peptide (ANP) concentrations change with extracellular fluid volume, suggesting that ANP continues to have a role in chronic renal failure. We have studied the effects of an infusion (5 pmol/kg per min) in subjects with chronic renal failure (CCr) less than 30 ml/min per 1.73 m2). Glomerular filtration rate and effective renal plasma flow increased by 23% (P less than 0.01) and 27% (P less than 0.01) respectively and sodium excretion more than doubled. Systolic and diastolic blood pressures decreased by 14 (SD 1.6) and 6 (SD 0.8) mmHg respectively (P less than 0.001), and plasma renin activity declined (P less than 0.01). Plasma ANP concentrations were elevated compared to normal subjects and reached a peak of 224 (SD 87) pmol/l at the end of the infusion. Plasma half-life was 4.8 (SD 2.7) min. Plasma concentrations are elevated in chronic renal failure and ANP may play a physiological role in controlling extracellular fluid volume and blood pressure.

Topics: Atrial Natriuretic Factor; Blood Pressure; Diuretics; Electrolytes; Hemodynamics; Humans; Kidney Failure, Chronic; Osmolar Concentration; Peptide Fragments; Renal Circulation; Renin

Atrial natriuretic peptide (ANP) is stored in atrial myocytes as a 126 amino acid precursor molecule (ANP 1-126) and is cleaved during its release into circulation into the biologically active C-terminal ANP (99-126) and the N-terminal counterpart, ANP (1-98). While interest has focused on ANP (99-126) under physiological and pathophysiological conditions, data for the cosecreted N-terminal sequence, ANP (1-98) are generally missing. Plasma levels of the N-terminal immunoreactive peptide (N-ANP [1-98]) were measured in normal dogs, and in dogs with impaired volume regulation (congestive heart failure; chronic renal failure or Cushing's syndrome and compared with those of C-ANP (99-126). The N-ANP (1-98) concentration was 593.1 +/- 81.1 fmol ml-1 in normal subjects, which is about 60-fold higher than the C-ANP (99-126) (10.8 +/- 2.6 fmol ml-1). In patients suffering from chronic renal failure ANP (1-98) was increased to 1582 +/- 196 fmol ml-1, and in dogs with congestive heart failure to 1612 +/- 244 fmol ml-1. In contrast, Cushing's syndrome dogs showed decreased N-ANP (1-98) concentrations (351 +/- 65.9 fmol ml-1). There was a positive correlation between plasma levels of N-ANP (1-98) and C-ANP (99-126) levels (correlation coefficients: normal: r = 0.78; congestive heart failure: r = 0.76; chronic renal failure: r = 0.86; Cushing's syndrome: r = 0.57). High pressure liquid chromatographic analysis of dog plasma showed one major peak of N-terminal immunoreactivity corresponding to ANP (1-98).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Atrial Natriuretic Factor; Chromatography, High Pressure Liquid; Cushing Syndrome; Diuretics; Dog Diseases; Dogs; Female; Heart Failure; Immune Sera; Kidney Failure, Chronic; Male; Peptide Fragments; Protein Precursors; Radioimmunoassay; Reference Values

In 11 patients with decompensated cirrhosis and deteriorating renal function, the effect of the vasoconstrictor substance 8-ornithin vasopressin (ornipressin; POR 8; Sandoz, Basel, Switzerland) on renal function, hemodynamic parameters, and humoral mediators was studied. Ornipressin was infused at a dose of 6 IU/h over a period of 4 hours. During ornipressin infusion an improvement of renal function was achieved as indicated by significant increases in inulin clearance (+65%), paraaminohippuric acid clearance (+49%), urine volume (+45%), sodium excretion (+259%), and fractional elimination of sodium (+130%). The hyperdynamic circulation was reversed to a nearly normal circulatory state. The increase in systemic vascular resistance (+60%) coincided with a decrease of a previously elevated renal vascular resistance (-27%) and increase in renal blood flow (+44%). The renal fraction of the cardiac output increased from 2.3% to 4.7% (P less than 0.05). A decline of the elevated plasma levels of noradrenaline (2.08-1.13 ng/mL; P less than 0.01) and renin activity (27.6-14.2 ng.mL-1.h-1; P less than 0.01) was achieved. The plasma concentration of the atrial natriuretic factor increased in most of the patients, but slightly decreased in 3 patients. The decrease of renal vascular resistance and the increase of renal blood flow and of the renal fraction of cardiac output play a key role in the beneficial effect of ornipressin on renal failure. These changes develop by an increase in mean arterial pressure, the reduction of the sympathetic activity, and probably of an extenuation of the splanchnic vasodilation. A significant contribution of atrial natriuretic factor is less likely. The present findings implicate that treatment with ornipressin represents an alternative approach to the management of functional renal failure in advanced liver cirrhosis.

Topics: Atrial Natriuretic Factor; Female; Hemodynamics; Humans; Kidney Failure, Chronic; Kidney Function Tests; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Ornipressin; Renal Circulation

Indirect evidence suggest that volume overload is the major determinant of plasma atrial natriuretic factor (ANF) elevation in hemodialysis patients. Correlations between plasma ANF levels and extracellular volume (ECV) were investigated by simultaneously measuring both parameters in 30 pediatric hemodialysis patients (aged 1 to 17.5 years; 18 M, 12 F) 24 hours after a dialysis session. Plasma ANF was determined using a commercially available RIA (Amersham) after plasma extraction (SEP-Pack C18); ECV was estimated by determining the volume of distribution of inulin and expressing the result as the % of body weight. In hemodialysis children, ANF levels ranged from 43 to 427 pg/ml (versus 30-70 pmoles/ml in age-matched controls) and EVC ranged from 17 to 33% BW. A significant positive correlation was found between plasma ANF levels and ECV (r = 0.66; p less than 0.001). Patients who exhibited falls in blood pressure during the dialysis session had lower mean ANF and ECV values (133 +/- 90 pg/ml and 23 +/- 3% BW, respectively) than those who did not (211 +/- 123 pg/ml and 26 +/- 4% BW, respectively). Conversely, patients who needed chronic antihypertensive therapy had higher mean plasma ANF and ECV values (204 +/- 122 pg/ml and 26 +/- 4% BW, respectively) than those who did not (149 +/- 100 pg/ml and 23. 5 +/- 4.5% BW, respectively). In a small subgroup of patients who had repeated determinations, individual plasma ANF and ECV changes were closely matched and both parameters were well correlated.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Atrial Natriuretic Factor; Body Weight; Child; Child, Preschool; Humans; Infant; Kidney Failure, Chronic; Plasma Volume; Renal Dialysis

Neuroendocrine activity in normal subjects was compared to patients with chronic renal failure on maintenance hemodialysis (CRF-HD) and to cyclosporine-treated renal transplantation (RT) recipients in an effort to further define the mechanisms underlying their associated fluid, electrolyte, and hemodynamic abnormalities. To evaluate neuroendocrine function in CRF and RT patients, plasma levels of angiotensin II (A-II), vasopressin (AVP), atrial natriuretic peptide (ANP), neuropeptide Y, neuropeptide Y (NPY), epinephrine (E), and norepinephrine (NE) were measured before and after HD and RT. Plasma concentrations of A-II, AVP, ANP, and NPY were significantly elevated in patients with CRF. HD did not produce a significant change in plasma concentrations of AVP, ANP, NPY, E, or NE. NE plasma levels, but not E levels, increased pre- and post-HD. A-II plasma levels were elevated basally in CRF patients and significantly increased following HD. Following RT, plasma levels of A-II, AVP, NPY, and creatinine decreased significantly over the first week, but AVP and NPY did not normalize. Plasma levels of ANP were elevated during the first month, then decreased to normal levels in RT patients. NE levels, but not E levels, were elevated both pre- and post-RT. Despite antihypertensive treatment, the group mean arterial pressure increased post-RT from 100 +/- 4.4 to 116 +/- 3.7 mmHg by POD 6.

Topics: Adult; Angiotensin II; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Cyclosporine; Epinephrine; Furosemide; Humans; Hypertension, Renal; Kidney Failure, Chronic; Kidney Transplantation; Methylprednisolone; Neurosecretory Systems; Norepinephrine; Prospective Studies; Radioimmunoassay; Renal Dialysis; Water-Electrolyte Balance

To determine the relationship between plasma immunoreactive atrial natriuretic peptide (i-ANP) and renin-angiotensin-aldosterone system (RAAS), plasma i-ANP, plasma renin activity (PRA) and plasma aldosterone (PA) were assayed in 29 patients (19 hypertensive and 10 normotensive) with chronic renal failure (CRF), and in 10 healthy subjects. Hypertensive patients had higher i-ANP values than normotensive patients and controls (P less than 0.05 and P less than 0.01 respectively). There was no significant correlation between plasma i-ANP and creatinine concentrations in hypertensive patients, whereas this correlation was statistically significant in normotensive patients (r = 0.70, P less than 0.01). Other positive correlations were between plasma i-ANP and systolic blood pressure in hypertensive patients (r = 0.69, P less than 0.01) and between plasma ANP and mean arterial pressure in normotensive patients (r = 0.63, P less than 0.01). There was significant negative correlation between plasma ANP and fractional sodium excretion (FENa) in hypertensive patients (r = -0.47, P less than 0.05), though there was significant positive correlation in normotensive patients (r = 0.80, P less than 0.01). Hypertensive patients, with the exception of one anuric patient and another with atrial fibrillation, had a significant negative correlation between FENa and systolic arterial blood pressure (r = 0.64, P less than 0.01). The patient group had increased PRA and PA values (P less than 0.01 and P less than 0.001 respectively) and showed positive correlation with mean arterial pressure (MAP) (r = 0.71, P less than 0.001 and r = 0.58, P less than 0.01 respectively). These results show that increased concentrations of immunoreactive ANP circulate in CRF together with activated RAAS. We demonstrate that elevated ANP cannot affect blood pressure and natriuresis in hypertensive patients with CRF, whose RAAS is activated.

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Humans; Hypertension; Kidney Failure, Chronic; Middle Aged; Natriuresis; Regression Analysis; Renin; Renin-Angiotensin System

The function of atrial natriuretic peptide (ANP) is claimed to be control of salt and water homeostasis, and thus, the hormone may be involved in the pathogenesis of certain diseases with impaired volume regulation. We, therefore, studied plasma ANP concentration in dogs with chronic renal failure, congestive heart failure, and hyperadrenocorticism. Dogs with chronic renal failure had twofold higher plasma ANP concentration (16.2 +/- 5.8 fmol/ml), compared with healthy dogs (8.3 +/- 3.5 fmol/ml). An even more distinct increase (sixfold) of plasma ANP concentration was found in dogs with congestive heart failure (52.9 +/- 29.7 fmol/ml). In contrast, dogs with hyperadrenocorticism did not have high ANP plasma concentration (5.5 +/- 2.0 fmol/ml). High-performance liquid chromatographic analysis of plasma from dogs with congestive heart failure indicated that, in addition to the normal circulating form of ANP (99-126), the unprocessed precursor ANP (1-126) is detectable in the circulation. These qualitative and quantitative alterations of plasma ANP concentration in dogs further suggest involvement of this peptide in the development and/or maintenance of diseases associated with impaired volume regulation.

Topics: Adrenocortical Hyperfunction; Animals; Atrial Natriuretic Factor; Chromatography, High Pressure Liquid; Dog Diseases; Dogs; Female; Heart Failure; Kidney Failure, Chronic; Ligands; Male; Radioimmunoassay

Plasma levels of immunoreactive atrial natriuretic peptide (IR-ANP) were measured with a specific radioimmunoassay in 19 undialysed patients with chronic renal failure. At the beginning, an extremely high level of plasma hANP (50 fmol/ml) seen in a patient was rejected with Smirnov's test and was excluded from further statistics. The plasma IR-ANP levels in these patients were significantly higher than those of 19 normal subjects matched with age and sex (10.9 +/- 1.6 vs 5.3 +/- 0.6 fmol/ml, mean +/- SEM, p less than 0.01), and positively correlated with mean blood pressure (r = 0.44, p less than 0.05) and the cardiothoracic ratio (r = 0.65, p less than 0.01), but did not correlate with creatinine clearance (r = -0.38, n.s.). Further, a significant correlation was observed between plasma IR-ANP and urinary protein output (r = 0.47, p less than 0.05). On the other hand, urinary protein output did not correlate significantly with variables such as mean blood pressure, the cardiothoracic ratio or creatinine clearance. Since it has been suggested that ANP enhances glomerular capillary permeability, increased ANP responding to volume overload in those patients may play an important role in increasing urinary protein excretion.

Topics: Adult; Age Factors; Aged; Aging; Atrial Natriuretic Factor; Blood Pressure; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Proteinuria; Radioimmunoassay; Sex Factors

Plasma atrial natriuretic peptide (ANP), cyclic guanosine monophosphate (GMP) and renin activity (PRA) were measured in 13 patients with mitral stenosis 24 h before and 48 h after balloon valvotomy resulting in a fall in LA pressure from 23.4 +/- 2.2 to 10.5 +/- 0.8 mmHg (P less than 0.01). Before treatment, plasma ANP was higher during ambulation (128.1 +/- 18.5 pg ml-1) than in the supine posture (93.3 +/- 15.0 pg ml-1; P less than 0.01) and did not diminish after return to the erect posture (86.4 +/- 14.1 pg ml-1). A physiological response was restored after valvotomy with ANP plasma levels of 49.2 +/- 7.8 pg ml-1 in the initial ambulant period, 63.1 +/- 12.6 pg ml-1 in the supine posture and 44.6 +/- 8.7 pg ml-1 in the final erect posture. Postural variations of cyclic GMP were parallel to those of ANP. In contrast, LA hypertension did not abolish PRA postural response. During the three successive periods of ambulation, supine posture and erect posture PRA was 5.4 +/- 1.0, 2.8 +/- 0.6 and 5.5 +/- 1.2 ng h-1 ml-1, respectively, before treatment, whereas after treatment the values measured were 10.3 +/- 2.9, 2.3 +/- 0.7 and 7.0 +/- 2.5 ng h-1 ml-1 respectively. Variations of plasma ANP, cyclic GMP and PRA in response to postural changes were also studied in 10 healthy volunteers and in 12 uraemic patients with high plasma ANP.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Atrial Natriuretic Factor; Cardiac Catheterization; Creatinine; Female; Guanosine Monophosphate; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Mitral Valve Stenosis; Posture; Reference Values

Plasma atrial natriuretic peptide (ANP) levels were measured in non-dialyzed and dialyzed chronic renal failure (CRF) patients and in normal subjects. Changes in plasma ANP in response to hemodialysis (HD) and to isolated ultrafiltration (UF) were also investigated in dialyzed CRF patients. Plasma ANP levels were significantly higher in 28 non-dialyzed CRF patients than in 27 normal subjects (mean +/- SEM, 174.0 +/- 25.9 vs 25.0 +/- 1.9 pg/ml, p less than 0.001). Plasma ANP levels did not correlate with blood urea nitrogen or serum creatinine, however patients with advanced renal failure (creatinine clearance less than 10 ml/min) with cardiomegaly (cardiothoracic ratio greater than 50%) or hypertension (BP greater than 140/90 mmHg) had significantly higher plasma ANP levels than those who were not. A 6-hour HD significantly decreased the plasma ANP level (423.4 +/- 71.3 to 220.6 +/- 40.0 pg/ml, p less than 0.001) and body weight in 21 dialyzed CRF patients, and the decrement in plasma ANP showed a positive correlation with the decrement in body weight (r = 0.425, p = 0.056). In 8 dialyzed CRF patients, we further performed a 1-hour isolated UF for removal of isoosmotic intravascular fluid without changes in the solute concentrations, followed by a subsequent 5-hour HD. The decrease in plasma ANP during the 1-hour UF period was 68% of the total ANP decrement for the whole 6-hour study. The average plasma ANP level was decreased with 94.6 +/- 42.5 pg/ml/kg/h in the UF period compared to 3.5 +/- 1.4 pg/ml/kg/h in the HD period (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Atrial Natriuretic Factor; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Ultrafiltration

Patients with end stage renal failure have elevated plasma levels of atrial natriuretic peptide (ANP) which seems to be a sensitive parameter of body fluid status. A prospective study comparing patients on hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) was still missing. Six identical patients (59 +/- 10 yrs, residual diuresis 1.3 +/- 0.61, 1 data expressed as means +/- SEM) were studied in the predialysis phase and under steady state conditions on HD and on CAPD. Plasma levels of ANP, cyclic guanosine monophosphate (cGMP), adrenaline, noradrenaline and dopamine were determined. Blood and dialysate samples were repeatedly taken. Ultrafiltration-volume, dry weight and blood pressure were not different between HD and CAPD. ANP and cGMP reached the highest plasma levels in the predialysis phase with 421 +/- 180 pg/ml and 19.8 +/- 6.4 pmol/ml and decreased after the onset of dialysis treatment. On HD mean ANP levels of 279 +/- 175 pg/ml were not significantly different from those on CAPD (320 +/- 213 pg/ml). However, cGMP concentrations on CAPD (15.7 +/- 5.4 pmol/ml) surpassed the values measured on HD (10.5 +/- 3.4 pmol/ml, p less than 0.05). Plasma noradrenaline was markedly elevated in the predialysis phase (421 +/- 180 pg/ml) and decreased under dialysis treatment. Differences between HD and CAPD were not found. Adrenaline and dopamine concentrations fell within the normal range.

Topics: Atrial Natriuretic Factor; Catecholamines; Cyclic GMP; Humans; Kidney Failure, Chronic; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis

The atrial natriuretic factor (ANF) is a hormone whose effects and mode of secretion have been determined. But its exact role in the regulation of volemia in comparison with that of the renin-angiotensin system is still to be defined. Studies of human diseases associated with an increase of ANF plasma concentration may help reach this goal. The mechanisms resulting in elevated ANF plasma concentrations (increase of secretion, decrease of catabolism of the hormone) and the effects of these high levels of ANF on renal functions and circulation are analysed in chronic cardiac failure, mitral stenosis, pulmonary artery hypertension, acute tachycardias, chronic and acute renal failures and in the course of cardiac transplantation. The therapeutic usefulness of drugs inhibiting ANF catabolism (blockers of the clearance receptors for ANF and inhibitors of the enzymes degrading ANF) is also considered.

Topics: Acute Kidney Injury; Atrial Natriuretic Factor; Heart Failure; Heart Transplantation; Humans; Hypertension, Pulmonary; Hypertension, Renovascular; Kidney Failure, Chronic; Mitral Valve Stenosis; Tachycardia, Supraventricular

The purpose of the present study was to assess the plasma levels of atrial natriuretic peptide (ANP) in chronically uremic patients not submitted to dialysis and to determine the predialysis plasma concentration of ANP, the effect of ultrafiltration on plasma levels of ANP (hemodialysis, (HD), and the HD clearance of ANP in a population of adult patients treated with maintenance HD. The mean plasma ANP concentration (pg/ml) in HD was 370.2 +/- 35.5 pg/ml (mean +/- SEM) before HD and decreased to 165.3 +/- 15.2 after HD (p less than 0.01). Both values were significantly higher than in controls (28 +/- 2; n = 39). The changes in plasma ANP levels correlated inversely with those in plasma protein concentration (r = -0.53; p less than 0.03; y = 48.6 +/- 0.8 x). ANP clearance across the cuprophan membrane averaged 13 +/- 6.4 ml/mn. Resting plasma ANP values in the 16 uremic patients ranged between 16 and 277 pg/ml (124 +/- 11 pg/ml). These levels were significantly higher than those observed in controls (p less than 0.01). In these patients there was a highly significant correlation between serum creatinine and plasma ANP concentrations (p less than 0.01; r = 0.75; y = 0.2x + 3). Furthermore we report the results of the determination of the renal clearance of ANP in normal dogs. In all dogs a fall in plasma ANP concentration was recorded between the aorta (28.6 +/- 4.5 pg/ml) and the renal vein (14.2 +/- 2.7 pg/ml). The renal extraction ratio averaged 51.3 +/- 3.7%. Mean ANP renal clearance was 38.2 +/- 5.2 ml/mn.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Atrial Natriuretic Factor; Dogs; Female; Humans; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

1. The natriuretic and diuretic effects of atriopeptin III (125, 250 and 500 ng kg-1, i.v.) were studied in groups of rats anaesthetized with pentobarbitone which were either sham controls, unilaterally nephrectomized controls, adenine-fed or subtotal nephrectomy chronic renal failure models. 2. Atriopeptin III given at these doses to the sham control animals had no effect on blood pressure, renal blood flow or glomerular filtration rate but reversibly increased urine flow, between 46% to 54%, absolute sodium excretion, between 52% to 61%, and fractional sodium excretion, between 48% to 54% (all P values less than 0.05) from the lowest to the highest dose. The adenine-fed chronic renal failure group of rats had a reduced renal blood flow of between 30 and 75%, and glomerular filtration rate of approximately 20%, compared to the sham controls. Administration of atriopeptin at 125, 250 and 500 ng kg-1 to the animals with renal failure increased water and sodium excretion to the same degree as observed in the sham group of rats. 3. In the group of unilaterally nephrectomized rats, atriopeptin III, at 125, 250 and 500 ng kg-1 increased urine flow by 36%, 47% and 72%, respectively, absolute sodium excretion by 37%, 57% and 106%, respectively, and fractional sodium excretion by 46%, 45% and 102%, respectively. A similar pattern of responses was observed in the subtotal nephrectomy, chronic renal failure group in which filtration rate was approximately 4 times less than the controls. 4. These results show that in two different models of chronic renal failure, atriopeptin III still caused a natriuresis and diuresis. This suggests that the nephrons retain sensitivity to the atrial natriuretic peptides in diseases such as chronic renal failure and that these compounds may be useful in mobilizing body fluids in this situation.

Topics: Adenine; Animals; Atrial Natriuretic Factor; Diuresis; Glomerular Filtration Rate; Kidney; Kidney Failure, Chronic; Kidney Function Tests; Male; Natriuresis; Nephrectomy; Nephrons; Rats; Rats, Inbred Strains

Since it remains unclear how the regulatory mechanism of blood pressure and volume is associated with the renin-angiotensin system, the sympathetic nervous system, and atrial natriuretic peptide (ANP), we examined the changes in blood pressure and vasoactive hormones occurring in 12 patients with end-stage renal failure. They were divided into two groups, those who were anuric (group A, n = 7), and those who had a daily urine volume of more than 700 ml (group B, n = 5). The changes in the mean blood pressure (MBP) and these vasoactive hormones were observed during hemodialysis with water removal in group A and without water removal in group B, and during blood pressure reduction with sodium nitroprusside in group A. The basal levels of ANP in groups A and B were twice as high as those of normotensive subjects. During hemodialysis, MBP did not reveal any changes in both groups. In group A, ANP and body weight (BW) decreased, whereas the plasma renin activity (PRA) and norepinephrine (NE) increased. In group B, ANP remained stable during the first 3 hr and decreased at the end of hemodialysis. However, BW, PRA, and NE were unchanged. In group A, significant correlations were observed between the changes in BW and those in ANP (r = 0.52, p less than 0.05), PRA (r = -0.57, p less than 0.01), and NE (r = -0.76, p less than 0.01). During blood pressure reduction, MBP decreased with accompanying increases in NE and PRA. However, ANP did not show any change.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Atrial Natriuretic Factor; Blood Pressure; Blood Volume; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Renin-Angiotensin System; Sympathetic Nervous System

In chronic renal failure, non-immunological mechanisms may cause disease progression. It is postulated that the high plasma levels of atrial natriuretic factor which occur in some patients with chronic renal impairment are biologically active. They would not only serve to maintain sodium balance but also alter glomerular haemodymanics and enhance proteinuria to the long-term detriment of renal function.

Topics: Animals; Atrial Natriuretic Factor; Humans; Kidney Failure, Chronic; Models, Biological

We have developed and validated a two-site liquid-phase immunoradiometric assay (IRMA) of atrial natriuretic peptide (ANP) in unextracted human plasma. Both radiolabeled rabbit anti-ANP IgG and polyclonal mouse anti-ANP must bind to ANP for detection, and the assay is specific for peptides with both an intact C-terminus and a disulfide bridge. The assay sensitivity (detection limit) is 0.96 pmol/L, and the working range is 2.3-300 pmol/L, with the hook effect occurring above 500 pmol/L. Results for diluted plasma from normal subjects and from patients with renal failure paralleled the standard curve; analytical recovery of ANP added to such samples averaged 94%. The between- and within-assay CVs at 8 pmol/L were 10% and 5%, respectively. The assay is sufficiently sensitive and precise to detect the postural change in ANP concentrations in normal subjects.

Topics: Atrial Natriuretic Factor; Female; Humans; Immunochemistry; Immunoradiometric Assay; Kidney Failure, Chronic; Male; Posture

Plasma immunoreactive human atrial natriuretic peptide (hANP) levels were measured in 9 patients with chronic renal failure treated with maintenance hemodialysis in order to evaluate the effects of fluid removal and osmotic pressure. Under hemodialysis without fluid removal plasma hANP levels remained unchanged, but the levels were significantly decreased during extra-corporeal ultrafiltration (p less than 0.01). The present study provided strong evidence that the fall in plasma hANP levels in hemodialysis patients is mainly due to the reduction in circulating plasma volume.

Topics: Adult; Aged; Atrial Natriuretic Factor; Body Weight; Extracorporeal Circulation; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Ultrafiltration; Vasopressins

About 30% of hemodialyzed patients are suffering from chronic fluid overload despite advice to restrict the oral fluid intake. To investigate the cause of the abnormal drinking behaviour a clinical study was performed in 51 non-diabetic patients with endstage renal disease exhibiting lower interdialysis weight gain (less than 3 kg, n = 17) and increased interdialysis weight gain (greater than 3 kg, n = 34). Blood pressure, body weight self-estimated thirst intensity before and after hemodialysis were analyzed. Biochemical and behavioral variables were measured including hormonal factors of water and sodium metabolism. Significant differences of dry weight, creatinine, urea nitrogen and thirst intensity were found between the two groups. Catecholamines, renin, angiotensin II, aldosterone, vasopressin and atrial natriuretic peptide exhibited a similar pattern in both groups. Atrial natriuretic peptide decreased during hemodialysis in both groups, angiotensin II, however, and norepinephrine showed an exaggerated response to ultrafiltration rate in polydipsic patients. These results suggest that changes in serum osmolality during hemodialysis did not contribute to thirst and drinking behaviour. It seems that postdialytic hypovolaemia together with higher plasma-angiotensin II-levels is responsible for increased oral intake of fluid and excessive weight gain.

Topics: Angiotensin II; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Chemical Analysis; Body Weight; Drinking Behavior; Humans; Kidney Failure, Chronic; Norepinephrine; Renal Dialysis; Renin; Thirst

Plasma levels of immunoreactive N-terminal ProANP have been measured in plasma from 19 healthy individuals, 15 patients with essential hypertension, 8 cardiac transplant recipients and 8 patients with chronic renal failure using two separate radioimmunoassays (RIAs), one directed against ProANP (1-30) and the other against ProANP (79-98). The mean concentrations of ProANP (1-30) and ProANP (79-98) were elevated in these groups of patients. There were positive correlations between levels of ProANP (1-30) and ProANP (79-98), with a correlation coefficient of 0.97 (P less than 0.001, n = 50). In healthy individuals a 2-1 (isotonic) saline infusion significantly increased both ANP (99-126) (P less than 0.05, n = 8) and N-terminal ProANP (P less than 0.005, n = 8) within 15 min of the end of the infusion. Plasma N-terminal ProANP levels were still significantly elevated after 75 min (P less than 0.05, n = 8) and 225 min (P less than 0.05, n = 8), by contrast ANP (99-126) had returned to basal values. Gel filtration of plasma extracted on Sep-Pak C-18 from normal individuals and patients gave a single immunoreactive peak for N-terminal ProANP as measured by both N-terminal ProANP assays, indicating an absence of small N-terminal fragments and the presence of a single high molecular weight form. These studies demonstrate that the major circulating N-terminal ANP in man is probably ProANP (1-98) and that it is cosecreted with ANP (99-126).

Topics: Adult; Aged; Atrial Natriuretic Factor; Chromatography, Gel; Female; Heart Transplantation; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Molecular Weight; Peptide Fragments; Protein Precursors; Radioimmunoassay; Sodium Chloride

N-Terminal pro ANP (atrial natriuretic peptide) in human plasma has been measured by radioimmunoassay after extraction on Sep-Pak cartridges. Immunoreactive N-terminal pro ANP circulates in human plasma at higher levels than alpha-hANP (approximately 20-fold higher in normal subjects) and was elevated in patients with essential hypertension, cardiac transplantation and patients with chronic renal failure. In chronic renal failure patients undergoing hemodialysis, C-terminal ANP (ANP 99-126), but not N-terminal ANP, declined significantly after dialysis. Gel filtration experiments demonstrated a single peak of N-terminal ANP immunoreactivity, eluting in parallel with synthetic human pro ANP 1-67, indicating a similar molecular size and the absence of low molecular weight N-terminal fragments.

Topics: Adolescent; Adult; Atrial Natriuretic Factor; Chromatography, Gel; Female; Heart Transplantation; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Peptide Fragments; Protein Precursors

The aim of the study was the search for the correlation between the degree of impairment renal function (measured by creatinine clearance) and plasma concentration of atrial natriuretic peptide (ANP) and urinary fractional sodium excretion (FENa) in patients with chronic renal diseases. Forty seven patients were studied: 10 with diminished renal reserve (group I), 10 with renal insufficiency (group II), 27 with renal failure (group III) and 10 chronically haemodialysed before dialysis (group IV). Control group consisted of 27 healthy persons. All patients and controls were on the diet containing 100-120 mmol sodium daily. Plasma ANP levels were significantly higher in all groups of patients (I--16.5 +/- 5.7; II--40.7 +/- 18.6; III--86.2 +/- 49.9; IV--196.1 +/- 51.3 pmol/l, respectively) than in controls (10.8 +/- 6.0 pmol/l). A significant correlation (r = 0.85; p less than 0.01) between plasma ANP concentration and FENa was found when the patients from all groups were pooled together. The results confirm the important role of ANP in the adaptation of reduced kidney mass to the excretion of sodium load.

Topics: Adult; Atrial Natriuretic Factor; Creatinine; Female; Humans; Kidney Failure, Chronic; Kidney Function Tests; Male; Metabolic Clearance Rate; Middle Aged; Sodium

1. In order to examine the potential role of atrial natriuretic factor in modulating the increased sodium excretion per nephron in chronic renal failure, we studied 12 uraemic patients on the last day of two successive 7 day periods during which their sodium intake was 100 and 20 mmol of sodium/day, respectively. 2. There was a parallel decrease from 6.31 +/- 0.75 to 2.17 +/- 0.32% in the fractional excretion of filtered sodium and from 234.4 +/- 74.9 to 80.6 +/- 20.3 pg/ml (supine position) or 140.1 +/- 43.6 to 60.7 +/- 14.6 pg/ml (upright position) in plasma atrial natriuretic factor. Both parameters were significantly correlated during the two periods of different sodium intake (P less than 0.05). The ratio of plasma guanosine 3':5'-cyclic monophosphate to plasma creatinine changed proportionally to plasma atrial natriuretic factor. Plasma aldosterone and plasma renin activity increased during the sodium-depleted period but only plasma renin activity was significantly correlated with fractional excretion of filtered sodium. 3. The predominant role of atrial natriuretic factor compared with that of aldosterone in the renal response to varying sodium intake is suggested both by regression analysis and by the effect of 5 day's treatment with a converting enzyme inhibitor (enalapril) in six other uraemic patients on a normal (100 mmol/day) sodium intake. Such treatment, although resulting in a significant increase in plasma renin activity and a significant decrease in plasma aldosterone, at least in the supine position, did not modify the fractional excretion of sodium and plasma atrial natriuretic factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aldosterone; Atrial Natriuretic Factor; Creatine; Cyclic GMP; Enalapril; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renin; Sodium; Sodium, Dietary

Thirty-seven patients with volume-retaining disorders (liver cirrhosis with ascites, n = 8; heart failure NYHA III-IV, n = 12; endstage renal failure, n = 17) and twelve healthy age-matched controls were given a small dose (33 micrograms) of hANF (human atrial natriuretic factor). We tested the resulting hemodynamic and renal effects as well as the effect on plasma cyclic GMP levels and compared them with the properties of platelet ANF receptors. The ANF injection evoked an increase in cyclic GMP plasma levels of 19.3 +/- 2.2 nM in healthy controls. This increase tended to be smaller in the cirrhosis group (15.5 +/- 3.3 nM) and in the heart failure group (16.8 +/- 2.3 nM) than in the dialysis group (20.5 +/- 2.5 nM). The invasion rates of cyclic GMP were comparable in all groups, but the evasion rates increased more in the heart failure and endstage renal failure groups (27.9 +/- 7.7 min and 26.1 +/- 3.4 min, respectively) than in the cirrhosis and control groups (14.9 +/- 1.9 min and 14.2 +/- 1.9 min, respectively). Patients with endstage renal failure and congestive heart failure showed a smaller decrease in diastolic blood pressure than controls and patients with liver cirrhosis. Renal actions of ANF were diminished in cirrhosis and heart failure patients. Binding capacities of platelet ANF receptors were higher in the control group (12.2 +/- 1.5 receptors/cell) than in the patient groups (cirrhosis, 7.8 +/- 1.2; endstage renal failure, 8.0 +/- 0.9; heart insufficiency, 8.0 +/- 1.0 receptors/cell), with no differences among the patient groups. Binding affinities were not significantly different. Correlation analysis showed that the relationship between the actions of ANF and the increases in plasma cyclic GMP levels is loose and cannot predict the hemodynamic or renal effects of exogenous ANF in a given patient. Although the behavior of plasma cyclic GMP levels fails to predict the responsiveness of the body to ANF in a given patient, it does reflect the differences between the patient groups and the control group. In contrast, we found no correlation between the properties of platelet ANF receptors and ANF action.

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Platelets; Cyclic GMP; Female; Heart Failure; Hemodynamics; Humans; Kidney Failure, Chronic; Liver Cirrhosis; Male; Middle Aged; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface; Recombinant Proteins; Water-Electrolyte Balance

Chronic renal failure (CRF) was induced in male wistar rats (Group I) by 5/6 nephrectomy and the sham-operated ones served as control (Group II). The results showed that in Group I, plasma atrial natriuretic peptide (ANP) levels increased progressively as the Scr was elevated. Plasma R-A rose simultaneously compared to the normal (P less than 0.001). At the 20th week after operation, urine volume and Na decreased significantly (P less than 0.05). The number of glomerular receptors decreased markedly at the 12th week (P less than 0.05) and 20th week (P less than 0.01). Our data suggest that in 5/6 nephrectomized rats, the elevation of plasma ANP level might be partly caused by the damage of glomerular ANP receptors, and the elevated plasma ANP could not play its role in diuresis, natriuresis, blood pressure depression and R-A inhibition as a result of the damage of kidney ANP receptors.

Topics: Animals; Atrial Natriuretic Factor; Autoradiography; Kidney Failure, Chronic; Kidney Glomerulus; Male; Nephrectomy; Rats; Rats, Inbred Strains; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface

The role of human atrial natriuretic peptide (alpha-hANP) in the regulation of blood pressure (BP) and extracellular fluid volume (ECFV) remains elusive. This is of particular interest in chronic renal failure, in which first, increased sodium and water retention plays a major pathogenetic role in the development of hypertension, and second, altered secretion and/or metabolism of alpha-hANP may contribute to fluid volume and BP regulation. In the present study the relationship between renal function, BP, and circulating alpha-hANP was investigated in 16 non-dialyzed patients with stable chronic renal failure (CRF) without edema. Analysis of potential molecular heterogeneity of immunoreactive (ir) ANP was performed by gel permeation chromatography of plasma extracts from normotensive patients with CRF. Serum creatinine concentrations averaged 435 +/- 76 mumol/l ranging from 127 to 1187 mumol/l, systolic and diastolic BP averaged 158 +/- 4 and 94 +/- 2 mmHg, respectively. Plasma alpha-hANP concentrations ranged from 5 to 75 with a mean of 23 +/- 4 pmol/l as compared to a mean of 10 +/- 1 pmol/l in healthy volunteers (p less than 0.05). A significant linear correlation between plasma alpha-hANP and serum creatinine concentrations (r = 0.92) was observed; a weaker correlation was found between mean arterial pressure and alpha-hANP (r = 0.66). Chromatographic analysis revealed considerable amounts of higher molecular weight circulating ir-ANP, approximately 15,000 Da, in addition to the biologically active small mol wt ANP.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Female; Half-Life; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Sodium

The effects of 4 h haemodialysis (15 patients) or 4 h haemofiltration (five patients) on plasma concentrations of atrial natriuretic peptide (ANP) were compared by means of a sensitive radioreceptor binding assay, and related to accompanying changes in body weight, blood pressure and plasma renin activity. Before dialysis, plasma ANP concentrations were considerably elevated: haemodialysis group 10-484 pmol/l (mean 156 pmol/l); haemofiltration group 72-320 pmol/l (mean 170 pmol/l). Although plasma concentrations of ANP fell markedly with treatment in both groups: post-haemodialysis 2-187 pmol/l (mean 67 pmol/l); post-haemofiltration 47-135 pmol/l (mean 79 pmol/l), after treatment it remained above the normal range in 14 of the 20 patients. Pretreatment plasma ANP was related to systolic blood pressure (r = 0.459; P less than 0.05) but bore no relationship to mean or diastolic blood pressure, or plasma renin activity. The fall in plasma ANP concentration during treatment correlated with the postural blood pressure drop after dialysis (r = 0.505; P less than 0.05), but was unrelated to changes in weight or plasma renin activity with haemodialysis or haemofiltration. Plasma ANP concentrations rose rapidly again in the 60 min after dialysis treatment, without change in body weight. These results show that high levels of biologically active ANP circulate in end-stage renal disease. The fact that these are not reduced to normal by haemodialysis or haemofiltration, despite restoration to normovolaemic or hypovolaemic state, suggests that the increased levels of ANP in end-stage renal failure are due to both hypervolaemia and other factors, which may include occult cardiac dysfunction and loss of renal clearance.

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Female; Hemofiltration; Humans; Kidney Failure, Chronic; Male; Middle Aged; Plasma Volume; Renal Dialysis; Renin

Water immersion (WI)-induced alterations of circulating plasma volume (PV), plasma renin activity (PRA), plasma levels of aldosterone (Ald), vasopressin (AVP) and atrial natriuretic peptide (ANP) were examined in 12 patients with noninflammatory acute renal failure (ARF) at the anuric/oliguric phase, in 20 hemodialyzed patients with chronic renal failure and in 15 healthy subjects. Patients with acute and chronic renal failure showed significantly elevated basal ANP concentrations (138.67 +/- 12.88 and 295.8 +/- 21.87 pg/ml, respectively) as compared with normals (74.54 +/- 4.1 pg/ml) and significantly elevated PRA (20.85 +/- 3.24 and 6.60 +/- 0.94 ng/ml/h, respectively versus 2.33 +/- 0.31 ng/ml/h), plasma levels of Ald (16.11 +/- 1.26 and 18.11 +/- 1.58 ng/dl, respectively versus 12.71 +/- 1.03 ng/dl) and AVP (6.95 +/- 0.62 and 6.08 +/- 0.54 pg/ml, respectively versus 2.68 +/- 0.48 pg/ml). After 2 hrs of WI a significant decline of PRA, Ald and AVP but an increase of ANP was noted in all examined groups. The absolute WI-induced increase in plasma ANP was significantly less marked in uremic patients than in normals. The endocrine profile of patients with ARF differed only quantitatively from that of patients with CRF both under basal and WI conditions. WI was followed by a significant increase of PV which was significantly more marked in patients with ARF (+ 16.42 +/- 1.73%) than in CRF (10.57 +/- 0.37%) and in normals (+11.3 +/- 1.6%). Only in healthy subjects a significant correlation was found between WI-induced changes of PV and ANP, PRA and Ald, and between PRA and AVP.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Kidney Injury; Adult; Atrial Natriuretic Factor; Humans; Immersion; Kidney Failure, Chronic; Renal Dialysis; Renin-Angiotensin System; Rest; Time Factors; Vasopressins

Using a cross-over protocol we repeatedly measured the plasma levels of alpha-hANP (atrial natriuretic peptide) during one week by radio-immunoassay in eight patients with end-stage renal disease treated with chronic hemodialysis or hemofiltration. Before each hemodialysis or hemofiltration session mean plasma ANP levels (353 +/- 112, and 337 +/- 99 pg.ml-1, respectively) were significantly above normal (50 - 166 pg.ml-1). In all but one patient, the values fell significantly towards but not reaching the normal range. Plasma ANP concentrations returned to normal at the end of the treatment in only two of the eight subjects. There was a positive correlation between the increase in body weight from one treatment to the next and the plasma ANP concentration (r = +0.35, p less than 0.05). The net loss of fluid volume during each treatment did not correlate significantly with the change in plasma ANP levels. There was no difference between hemodialysis and hemofiltration. Plasma ANP measurement may be helpful in the judgement of volume status in patients with end-stage renal disease treated by hemodialysis or hemofiltration.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Body Weight; Female; Heart Rate; Hemofiltration; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

The present experiments were performed to clarify the renal and hemodynamic effects of atrial natriuretic peptide (ANP) in dogs with chronic renal failure (CRF; produced by 5/6 nephrectomy 3-4 weeks before study). Synthetic alpha-hANP was administered intravenously (0.1 micrograms/kg body weight for 30 min) with a priming bolus injection (1.0 micrograms/kg body weight) to anesthetized controls (n = 8) and CRF-dogs (n = 10). The effects of ANP on renal function, cardiac function, lithium clearance, and plasma ANP levels during clearance studies were determined. Effects of ANP on the hemodynamics were observed to the same degree in both groups. An increase in inulin clearance (CIn) was noted only in the CRF-dogs (7.5 +/- 2.1 to 9.6 +/- 2.9 ml/min; p less than 0.01). The infusion of ANP increased the urine volume, absolute sodium excretion, and osmolar clearance in the control and CRF groups. The fractional excretion of lithium (FELi), a marker of the proximal reabsorption of sodium, was higher at baseline in the CRF group (control group, 24.4 +/- 6.7 vs. CRF group, 41.5 +/- 13.2%; p less than 0.001). Following ANP infusion, FELi increased in both groups. The plasma ANP levels were monitored during the clearance study, and those of the CRF group were higher throughout the experiments. Thus, extrinsic ANP induced diuresis and natriuresis in CRF-dogs, produced by nephron mass reduction. Discrepancies in the pattern of response and plasma ANP levels were observed between the controls and CRF-dogs, suggesting that the action and metabolic clearance rate of ANP were altered in the CRF state.

Topics: Animals; Atrial Natriuretic Factor; Diuresis; Dogs; Hemodynamics; Kidney; Kidney Failure, Chronic; Natriuresis

Plasma concentrations of atrial natriuretic peptide (ANP), arginine vasopressin (AVP), plasma renin activity (PRA) and aldosterone, were measured before and after 3 h of hemodialysis in 9 patients with end-stage renal disease on maintenance hemodialysis. Hormone concentrations were also determined in the same patients on a separate occasion after 1 h of ultrafiltration (UF). Plasma concentrations of ANP were significantly higher in the patients with ESRD than in a normal reference population and declined after both 1 h and 3 h of hemodialysis. Plasma concentrations of ANP failed to exhibit a significant decline after 1 h of UF. Plasma AVP concentrations were not significantly different after either hemodialysis or UF, while plasma aldosterone concentrations fell with hemodialysis. The decline in plasma aldosterone concentrations paralleled the decrease in dialysis-induced fall in serum potassium concentrations. There was no correlation between the blood pressures, heart rate, interdialytic weight gain and estimated fluid overload and any of the hormones measured except for the plasma renin activity (PRA) which correlated significantly with the systolic blood pressure. The data suggest that ANP may not be a major factor in blood pressure regulation in normotensive patients with ESRD and its elevation in patients with ESRD is most likely due to fluid overload and atrial distention as well as a possible reduction in its metabolic clearance in renal insufficiency. The fall in plasma ANP following hemodialysis is not due to its removal by dialysis but is most likely due to a reduction in ANP production caused by dialysis-induced correction of hypervolemia.

Topics: Adult; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Female; Heart Rate; Hemofiltration; Humans; Kidney Failure, Chronic; Male; Middle Aged; Radioimmunoassay; Renal Dialysis; Renin-Angiotensin System; Weight Loss

To clarify the molecular nature and dynamics of circulating alpha human atrial natriuretic polypeptide (alpha hANP) in chronic renal disease, the plasma concentrations of alpha hANP were determined by radioimmunoassays using two distinct monoclonal antibodies (MoAbs). One MoAb (10B1) recognized N-terminus of alpha hANP, while the other (C351) recognized the ring structure. The preliminary studies revealed a close correlation (r = 0.97, p less than 0.0001) between plasma alpha hANP measured with 10B1 and C351 MoAbs, supporting the theory that the main circulating form is alpha hANP(1-28). Therefore, the more sensitive radioimmunoassay using MoAb (C351) was used in the present studies. The plasma alpha hANP was 3.8 +/- 1.7 (mean +/- SD) in healthy subjects, 2.7 +/- 1.4 fmol/ml in patients with chronic glomerulonephritis without renal failure, 16.2 +/- 16.8 fmol/ml in patients with chronic renal failure, and 24.3 +/- 10.5 fmol/ml in patients under maintenance hemodialysis. Thus, the elevation of plasma alpha hANP was related to the stages of renal damage. Although the plasma alpha hANP in 18 patients under maintenance hemodialysis declined significantly (p less than 0.01) after hemodialysis, their levels (17.9 +/- 9.0 fmol/ml) after hemodialysis were still higher than those in healthy subjects. On the other hand, a positive correlation (r = 0.65, p less than 0.05) between alpha hANP and creatinine in blood was found only in the group of chronic renal failure before maintenance hemodialysis. These results suggest that an impaired metabolism of alpha hANP in the kidney might play an important role in the elevation of plasma alpha hANP as well as the stimulation of alpha hANP secretion caused by the expansion of extracellular fluid.

Topics: Adult; Antibodies, Monoclonal; Antibody Specificity; Atrial Natriuretic Factor; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Radioimmunoassay; Renal Dialysis

The relationship between inferior vena cava diameter (VCD), collapse-index (CI) determined by echography, and alpha-human atrial natriuretic peptide (alpha-h-ANP) concentrations were studied in 19 chronic haemodialysis patients. A significant correlation was found between VCD and alpha-h-ANP before dialysis (r = 0.78; P less than 0.0001). No such correlation was found between CI, left atrial diameter and left ventricular end-diastolic diameter, and alpha-h-ANP values. In nine patients who according to vena cava indices were hypervolaemic before dialysis (group I), alpha-h-ANP concentrations were significantly greater than in ten normo- or hypovolaemic patients (group II): 392.8 +/- 134.1 pg/ml and 168.0 +/- 62.5 pg/ml respectively. Although the same amount of fluid was ultrafiltrated in both groups, alpha-h-ANP decreased significantly in group I only, whereas in group II the decrease was not significant: 392.8 +/- 134.1 to 185.2 +/- 81.7 (P less than 0.001); 168.0 +/- 62.5 to 130.0 +/- 59 respectively. After achieving normovolaemia alpha-h-ANP concentrations in patients with a mitral valve insufficiency grade I was doubled compared to normovolaemic patients without mitral valve insufficiency, suggesting that alpha-h-ANP release will also occur from the left atrium. In the latter group alpha-h-ANP values were approximately doubled compared to healthy controls. The highly significant correlation between VCD before dialysis and changes in alpha-h-ANP during dialysis with fluid removal underlines the value of vena cava diameter in estimating volume status.

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Blood Volume; Cardiac Output; Female; Heart Rate; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Ultrasonography; Vena Cava, Inferior

1. Plasma levels of immunoreactive N-terminal pro-atrial natriuretic peptide (N-terminal ANP) have been measured in 25 normal subjects, 29 patients with essential hypertension, six cardiac transplant recipients, seven patients with dialysis-independent chronic renal failure and 11 patients with haemodialysis-dependent chronic renal failure. Plasma was extracted on Sep-Pak cartridges and N-terminal ANP immunoreactivity was measured using an antibody directed against pro-ANP (1-30). 2. Plasma levels of N-terminal ANP (means +/- SEM) were 235.3 +/- 19.2 pg/ml in normal subjects and were significantly raised in patients with essential hypertension (363.6 +/- 36.3 pg/ml), in cardiac transplant recipients (1240.0 +/- 196.2 pg/ml), in patients with chronic renal failure not requiring dialysis (1636.6 +/- 488.4 pg/ml) and patients with chronic renal failure on maintenance haemodialysis (10336.1 +/- 2043.7 pg/ml). 3. There were positive and significant correlations between the plasma levels of N-terminal ANP and alpha-human ANP (alpha-hANP) with individual correlation coefficients of 0.68 within the normal subjects, 0.47 in patients with essential hypertension, 0.78 in patients with dialysis-independent chronic renal failure and 0.68 in patients with haemodialysis-dependent chronic renal failure (P less than 0.05 in every case).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Atrial Natriuretic Factor; Chromatography, Gel; Female; Heart Transplantation; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Natriuresis; Peptide Fragments; Protein Precursors; Reference Values

In a study of the role of atrial natriuretic peptide (ANP) in sodium homeostasis in experimental renal failure, we found that a infusion of ANP at 0.25 microgram/min for 15 min produced an increase in the glomerular filtration rate (GFR) and fractional excretion of sodium (FENa) in five-sixth nephrectomized (5/6 Nx) rats. Renal vascular resistance (RVR) was lower during the base-line period and did not change after the administration of 100 ng/ml ANP to isolated perfused kidney (IPK) from adriamycin-treated rats. Furthermore, fractional excretion of ANP (FEANP) by IPK decreased in kidneys from adriamycin-treated rats as compared to that in kidneys from control rats. Finally, after 5/6 Nx, levels of plasma immunoreactive ANP (ir-ANP) gradually increased but excretion of water and sodium did not change during normal intake of sodium. The increase in levels of ir-ANP was accompanied by an increase in the rates of excretion of water and sodium was observed 2 days later but these rates returned to the base-line values after 2 weeks. These findings suggest that ANP plays an important role in the adjustment of acute changes in the volume of extracellular fluid during experimental renal failure.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Diuresis; Doxorubicin; Glomerular Filtration Rate; Homeostasis; Kidney; Kidney Failure, Chronic; Kinetics; Male; Natriuresis; Nephrectomy; Rats; Rats, Inbred Strains; Sodium; Vascular Resistance

Changes of plasma atrial natriuretic factor (ANF) levels in 89 patients with different kinds of renal diseases (including 39 patients treated with hemodialysis) were studied. The results showed: 1. The mean value of plasma ANF level was significantly increased in patients with renal diseases than that in healthy subjects. The increase was positively correlated with the change of creatinine, serum potassium, mean arterial pressure and ptfV1. The plasma ANF level was markedly decreased after hemodialysis. 2. The right atrial pressure of 8 patients with chronic renal failure measured by right heart catheterization was normal. No significant changes occurred after hemodialysis. 3. Impedance cardiogram and mechanical cardiogram showed that left heart function was significantly improved after hemodialysis. 4. ANF was detected in ultrafiltration liquid. 5. There was no difference of the ANF content between the serum of the first and maintenance hemodialysis. The authors thought that the main causes of increase of plasma ANF level are decrease of catabolic metabolism in renal failure, stimulation of ANF secretion by left heart failure and increased loading of left atrium and increased production of ANF by body compensation as the result of mean arterial pressure increase. The decrease of ANF after hemodialysis was mainly due to improvement of renal and cardiac function, lessening of the left atrial loading, the reduced mean arterial pressure and its direct elimination by hemodialysis.

Topics: Adolescent; Adult; Aged; Atrial Natriuretic Factor; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

Plasma atrial natriuretic factor (ANF), blood pressure, age, plasma renin activity and creatinine were measured in 50 normal volunteers, 141 essential hypertensives, 35 patients with chronic renal failure who had never been dialysed and 27 patients with end-stage renal failure on constant haemodialysis. Plasma ANF was correlated positively with age in the normal group (r = 0.52, P less than 0.01) and with blood pressure in the essential hypertensives (r = 0.50, P less than 0.001), and negatively with renin in the normal and end-stage renal failure patients (r = -0.47, r = -0.34; P less than 0.01, P less than 0.05, respectively). When patients without left ventricular hypertrophy were matched for age and blood pressure, plasma ANF was significantly different between the essential hypertensives and the normal and end-stage renal failure patients (16 +/- 1, 38 +/- 6 and 148 +/- 24 pmol/l, respectively; P less than 0.001). Cardiac factors are therefore not the only determinant of circulating plasma ANF in humans with chronic renal failure.

Topics: Aging; Atrial Natriuretic Factor; Blood Pressure; Creatinine; Humans; Kidney; Kidney Failure, Chronic; Renal Dialysis; Renin

In order to evaluate the possible role of vasoactive hormones in the mechanism of exaggerated sodium loss due to reduced renal mass we measured plasma concentration of atrial natriuretic peptide (ANP), aldosterone, plasma renin activity (PRA), plasma noradrenaline, and dopamine, in 12 children with advanced chronic renal failure (mean CIn 17.8 +/- 2.6, mean +/- SEM, CPAH 93.5 +/- 17 ml/min per 1.73 m2, FENa 7.0 +/- 0.95%). No patient had clinical signs of volume overload. Plasma concentrations of ANP were not significantly different from those of healthy age-matched controls (29.2 +/- 7.2 vs 23.2 +/- 3.1 fmol/ml) and did not correlate with urinary sodium excretion. Plasma concentrations of aldosterone, PRA and noradrenaline, were also within the physiological range, while plasma dopamine levels were elevated (260 +/- 36 vs 98 +/- 11 pg/ml, less than 0.001). Our data do not support the notion that ANP or the renin-aldosterone axis play a major role in the adaptation of remaining nephrons to maintain long-term sodium balance in normotensive children with chronic renal failure.

Topics: Adaptation, Physiological; Adolescent; Adult; Atrial Natriuretic Factor; Child; Child, Preschool; Dopamine; Female; Homeostasis; Humans; Kidney Failure, Chronic; Male; Natriuresis; Norepinephrine; Renin-Angiotensin System; Sodium

Circulating digitalislike immunoreactive substances (DLIS) may represent a class of volume-sensitive natriuretic factors. Chronic renal failure patients are known to have elevated levels of circulating natriuretic activity and also to have detectable DLIS. Using digoxin radioimmunoassay, DLIS levels were measured in desalted, deproteinized plasma from 15 stable hemodialysis patients. Predialysis DLIS was 109.3 +/- 6.3 pg/mL (digoxin equivalents) and decreased to 97.5 +/- 5.9 pg/mL following dialysis (P less than 0.001). Predialysis DLIS correlated with weight gain from the prior dialysis (P less than 0.01). The degree of extracellular fluid volume expansion predialysis also correlated with predialysis DLIS (P less than 0.01). Postdialysis DLIS also correlated with postdialysis extracellular fluid volume status (P less than 0.01). DLIS levels in dialysis patients were higher than in 50 normal subjects (30.0 +/- 1.2 pg/mL; P less than 0.001). Also, the changes in DLIS with dialysis were paralleled by similar changes in simultaneously measured human alpha-atrial natriuretic peptide (ANP) levels. These results demonstrate that (1) DLIS levels are higher in hemodialysis patients than in normal individuals; (2) with dialysis, DLIS levels increase and decrease in association with extracellular fluid volume expansion and removal, respectively; (3) DLIS levels correlate with the degree of extracellular fluid volume expansion in dialysis patients; and (4) DLIS levels change in parallel with levels of another class of natriuretic factor ANP. These characteristics are consistent with the hypothesis that DLIS represents a volume-sensitive factor.

Topics: Adult; Atrial Natriuretic Factor; Blood Proteins; Cardenolides; Digoxin; Extracellular Space; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Radioimmunoassay; Renal Dialysis; Saponins; Sodium-Potassium-Exchanging ATPase

The role of atrial peptide in humans with chronic renal insufficiency is uncertain. Therefore, the effects of synthetic atrial peptide (atriopeptin III, 24 amino acids) infusion on renal function and solute excretion were examined in 16 subjects with chronic renal insufficiency of diverse etiologies. After a two-hour baseline period, atrial peptide was infused for four hours in doses ranging from 0.005 to 0.1 micrograms/kg/min. When all doses were combined, absolute and fractional excretions of sodium increased significantly from baseline values (130 +/- 15 to 231 +/- 28 microEq/min and 3.57 +/- 0.57 to 6.03 +/- 1.26%, respectively, P less than 0.05). Significant increases in urinary excretion of chloride, calcium, and phosphorus were also seen during atrial peptide infusion. Increased absolute and fractional phosphorus excretion persisted during the two-hour postinfusion period, while excretion of other solutes returned to baseline. Glomerular filtration rate (GFR) increased by greater than 20% in five of 16 subjects. Two subjects with severe renal insufficiency (GFR = 9 and 12 mL/min) had no apparent response to atrial peptide infusion. Subjects receiving doses of 0.05 and 0.1 microgram/kg/min had significant falls of mean arterial pressure by the last hour of infusion. A dose-dependent effect of atrial peptide on sodium excretion was suggested, but not statistically significant. No apparent dose-dependent effect was seen on GFR or other solute excretions. Despite the presence of chronic renal insufficiency, atrial peptide increased renal solute excretion in most subjects. The demonstration that atrial peptide retains its diuretic and natriuretic effect in the presence of renal insufficiency supports the hypothesis that atrial peptide plays an important adaptive role in sodium homeostasis of the failing kidney.

Topics: Adult; Aged; Atrial Natriuretic Factor; Cyclic AMP; Cyclic GMP; Diuresis; Electrolytes; Hemodynamics; Humans; Kidney; Kidney Failure, Chronic; Middle Aged; Natriuresis; Osmolar Concentration

The authors measured the plasma levels of calcitonin gene-related peptide (CGRP), the most potent vasodilatator known, during sequential ultrafiltration and haemodialysis in 12 patients using a radio-immunoassay method. Mean plasma levels of CGRP were 70.3 +/- 16.5 (mean +/- SE) pmol l-1 at the start of treatment, it increased to 85.3 +/- 17.6 pmol l-1 during ultrafiltration and to 114.5 +/- 25.3 pmol l-1 during dialysis. Systolic blood pressure decreased during haemodialysis. Plasma levels of CGRP were negatively correlated to systolic blood pressure before and at the end of dialysis, and changes in plasma levels of CGRP were strongly correlated to changes in systolic blood pressure. The increase in CGRP levels was not correlated to the fluid removal, toxin removal or changes in osmolality. The increase in plasma levels of CGRP observed during dialysis may be an important cause of dialysis induced vasodilatation and fall in blood pressure.

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Blood Volume; Calcitonin Gene-Related Peptide; Female; Glomerulonephritis; Heart Rate; Humans; Kidney Failure, Chronic; Male; Middle Aged; Neurokinin A; Renal Dialysis; Ultrafiltration

Atrial natriuretic peptide (ANP) is a hormone liberated from the heart during atrial stretch (volume overload). In order to determine if ANP levels are altered in patients on continuous ambulatory peritoneal dialysis (CAPD) or affected by the dialysis procedure itself, we measured plasma ANP in patients before and after peritoneal infusion of two liters of 1.5% Dianeal dialysate and in dialysate subsequently drained from these patients. Plasma ANP is elevated in CAPD patients, but is not affected by infusion of dialysate. ANP is cleared from plasma by peritoneal dialysis.

Topics: Adult; Aged; Atrial Natriuretic Factor; Dialysis Solutions; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis

Plasma atrial natriuretic peptide (ANP) and digoxin-like immunoreactive substances (DLIS) levels were assayed in 10 patients on intermittent peritoneal dialysis (IPD) before and after a 12 hour dialysis session. Ultrafiltration volumes and blood pressures, pre and post dialysis were recorded. Left atrial diameter (LAD), as determined by M-mode echocardiography was measured prior to and at the end of each dialysis session. Ten age matched patients on hemodialysis (HD) served as controls. Predialysis plasma ANP was significantly higher in HD as compared to IPD patients and dialysis resulted in a significant decrease of plasma ANP in IPD and HD patients (37.9 +/- 28.0 to 23.1 +/- 28.5 and 201.9 +/- 110.7 to 117.0 +/- 75.6 pg/ml, respectively, p less than 0.05). Ultrafiltration volumes in IPD averaged 1840 +/- 645 ml/dialysis. The corresponding decrease in body weight in HD was 2000 +/- 220 g. Total DLIS levels in IPD and HD did not change with dialysis. LAD decrease significantly post dialysis (41.3 +/- 5.0 to 38.6 +/- 5.7 cm, p less than 0.001). Calculated ANP clearance during IPD was 5.6 +/- 3.9 ml/min. Plasma ANP correlated significantly with ultrafiltration volumes and LAD. It thus appears that ANP is sensitive to volume status in dialysed patients. Its dialysance, in IPD, approaches that of other middle molecules. Under the conditions tested ANP does not influence DLIS levels.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Blood Pressure; Blood Proteins; Cardenolides; Digoxin; Echocardiography; Female; Heart Atria; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis; Saponins

The changes in plasma atrial natriuretic peptide (ANP) were studied in four adult patients after cadaveric renal transplantation. In three patients who achieved good renal function, the correction of volume overload, as reflected by reduction in weight and right atrial pressure, was associated with a steady fall in plasma ANP and a parallel decrease in both fractional excretion of sodium and plasma cyclic guanosine monophosphate. The fourth patient, with severe acute rejection, developed severe peripheral oedema, and fractional sodium excretion remained low despite high values of ANP.

Topics: Adult; Atrial Natriuretic Factor; Cyclic GMP; Graft Survival; Humans; Kidney Failure, Chronic; Kidney Transplantation; Middle Aged; Plasma Volume

This highly sensitive radioreceptor assay (RRA) for the active circulating form of atrial natriuretic factor (ANF), fragment 99-126, in human plasma requires 125I-labeled ANF, bovine zona-glomerulosa membrane receptors, and amiloride HCl. The amiloride elicits an increase in the binding affinity of ANF to its receptors. ANF is extracted from human plasma with "Sep-Pak" cyano cartridges. After a 90-min incubation at 25 degrees C, bound and free fractions are separated by filtration. The ANF concentration that inhibits receptor binding of the radioligand by 50% is 12.4 fmol of unlabeled ANF per tube. The minimum detectable concentration is 0.2 fmol per tube. Using ANF-supplemented plasma samples, there was a good correlation (r = 0.99) between ANF concentrations found and those expected. Only the active circulating form of ANF fully cross-reacts in this assay, which confirms its high selectivity. Results correlated strongly (r = 0.93) for clinical samples tested by RRA and RIA.

Topics: Adrenal Cortex; Animals; Atrial Natriuretic Factor; Cattle; Chromatography, High Pressure Liquid; Cross Reactions; Humans; Kidney Failure, Chronic; Methods; Phenylephrine; Radioimmunoassay; Radioligand Assay; Reagent Kits, Diagnostic; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface

ANP and c-GMP concentrations in 7 patients with chronic renal failure (CRF) undergoing regular hemofiltration (HF) were determined. After switching to hemodialysis (HD) under identical ultrafiltration and treatment time no significant difference of the ANP and c-GMP profiles was detected, suggesting that the type of treatment does not affect ANP and c-GMP plasma levels. In both procedures a continuous decrease of ANP and c-GMP was observed. Head down tilting to compensate hypotension during HD was immediately followed by an increase in ANP and c-GMP during ultrafiltration. An acute onset of tachyarrhythmia absoluta during HD was also accompanied by a rise in ANP plasma concentrations. This demonstrates that ANP secretion is not altered in patients with CRF. Since ANP plasma levels closely correlate with intravascular volume, periodic determination of this hormone in HD/HF patients may provide diagnostic information to detect volume overload.

Topics: Atrial Natriuretic Factor; Cyclic GMP; Hemofiltration; Humans; Kidney Failure, Chronic; Radioimmunoassay; Renal Dialysis

To elucidate further the possible role of atrial natriuretic peptide (ANP) and hypothetical natriuretic hormone (NH) in volume and BP regulation in chronic renal failure (CRF) we measured plasma ANP, digitalis-like substances (DLS) and Na+-K+-ATPase activity (using 86Rb influx into RBC) in 9 patients with CRF before and after hemodialysis. Volume expansion between consecutive dialyses led in all patients to the elevation of plasma ANP (83.4 +/- 14.2 pmol/l) reaching in some overhydrated subjects and/or patients with concomitant cardiac insufficiency concentration greater than 150 pmol/l. Reduced 86Rb influx into RBC before hemodialysis (37.7 +/- 4.9% of controls) was accompanied by higher DLS concentrations (201 +/- 32 pmol/l). Ultrafiltration during hemodialysis with ECFV reduction lowered both ANP and DLS concentrations to 28.1 +/- 9.4 pmol/l and to 151 +/- 23 pmol/l, respectively, and abolished partly the inhibition of Na+-K+-ATPase activity (64.9 +/- 7.6% of controls). These changes corresponded to the degree of ECFV alteration. Our results suggest that both natriuretic principles are activated during ECFV expansion in CRF, probably as a corrective mechanism, with a tendency to normalize when ECFV is reduced during hemodialysis.

Topics: Adult; Atrial Natriuretic Factor; Blood Proteins; Cardenolides; Digoxin; Erythrocytes; Female; Humans; Kidney Failure, Chronic; Male; Natriuretic Agents; Renal Dialysis; Saponins; Sodium-Potassium-Exchanging ATPase

To study the role of alpha-human atrial natriuretic polypeptide (alpha-hANP) in body fluid regulation, we measured the plasma concentration of alpha-hANP and renal function in 9 patients with congestive heart failure (CHF), 10 with chronic renal failure (CRF) and 8 normotensives (NT) before and during alpha-hANP infusion at 0.025 microgram/kg.min. The plasma concentration of alpha-hANP was significantly higher in the CHFs and CRFs than in the NTs (319, 168 and 72 pg/ml, respectively). Alpha-hANP infusion decreased mean blood pressure in a similar manner in the 3 groups (-5%, p less than 0.01 each). Increases in urinary sodium excretion and glomerular filtration rate during alpha-hANP infusion, however, were greater in the CHFs and CRFs than in the NTs. Furthermore, the higher the preinfusion level of renal vascular resistance (RVR), the greater was the reduction in RVR by alpha-hANP (r = -0.80, p less than 0.001). The metabolic clearance rate (MCR) of alpha-hANP was significantly smaller in the CHFs and CRFs than in the NTs (38, 35 and 67 ml/min.kg, respectively). These results suggest that the renal vasodilatory actions of alpha-hANP seem to be enhanced in patients with increased RVR and that the elevation of the basal plasma concentration of alpha-hANP in CHFs and CRFs may be in part due to the low MCR.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Cyclic GMP; Glomerular Filtration Rate; Heart Failure; Humans; Infusions, Intravenous; Kidney; Kidney Failure, Chronic; Metabolic Clearance Rate; Middle Aged; Natriuresis; Renal Circulation; Vascular Resistance; Vasodilation

Two peptides consisting of amino acids 1-30 and 31-67 of the N-terminal end of the prohormone of atrial natriuretic factor (pro ANF) which vasodilate aortas in vitro, lower blood pressure in vivo, and have natriuretic properties were found to circulate in 54 normal human volunteers. The mean circulating concentration of pro ANF 1-30 was 1861 +/- 87 pg/ml (SEM) while pro ANF 31-67 mean concentration was 1478 +/- 71 pg/ml versus a level of 67 +/- 3 pg/ml for atrial natriuretic factor (ANF). In chronic renal failure their mean concentrations increased to 40,484 +/- 6,929 pg/ml (SEM), 108,566 +/- 16,888 pg/ml, and 348 +/- 81 pg/ml for pro ANFs 1-30 and 31-67 and ANF respectively. Since pro ANF 1-30 and pro ANF 31-67 circulate in man and have physiologic effects they meet the criteria of two new hormones.

Topics: Adult; Atrial Natriuretic Factor; Contraceptives, Oral; Female; Humans; Kidney Failure, Chronic; Male; Peptide Fragments; Protein Precursors; Reference Values; Smoking

The relationship between kidney function and plasma immunoreactive atrial natriuretic factor (irANF) levels as well as the effects of synthetic human ANF-(99-126) were investigated in 13 patients with mild to moderate chronic renal failure. Under basal conditions, glomerular filtration rate averaged 39 +/- 5 (SEM) ml/min/1.73 m2 and blood pressure (BP) averaged 166/107 +/- 7/2 mm Hg; 12 patients were hypertensive. Plasma irANF levels were significantly increased (98 +/- 16 vs 42 +/- 4 pg/ml in healthy control subjects; p less than 0.001) and correlated (p less than 0.05-0.005) inversely with hematocrit (r = -0.65) and positively with systolic BP (r = 0.75) or fractional sodium excretion (r = 0.75). Human ANF-(99-126) infusion for 45 minutes at 0.034 microgram/kg/min augmented (p less than 0.05-0.01) diuresis and urinary sodium, chloride, calcium, phosphate, and magnesium excretion. During the subsequent 45 minutes of human ANF-(99-126) infusion at a rate of 0.077 microgram/kg/min, diuresis and electrolyte excretion remained elevated (p less than 0.05-0.01). Glomerular filtration rate and effective renal plasma flow were not significantly modified, but filtration fraction rose progressively (p less than 0.01). Human ANF-(99-126) infusion decreased BP (p less than 0.05-0.01), produced hemoconcentration (hematocrit + 7%; p less than 0.01) without negative body fluid balance, and increased (p less than 0.01-0.001) plasma norepinephrine, insulin, and serum free fatty acids; plasma aldosterone and renin activity were unaltered during but rose after cessation of human ANF-(99-126) infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Female; Glomerular Filtration Rate; Hematocrit; Homeostasis; Humans; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Norepinephrine; Peptide Fragments; Renin; Sodium

We explored the effects of 12-hour infusion of atrial natriuretic peptide (alpha-rANP:rat, 1-28) on arterial acid-base balance, using 5/6 nephrectomized rats with chronic renal failure. Before the infusion, nephrectomized rats had a higher mean arterial blood pressure, greater urine volume, and lower creatinine clearance than the normal controls, but they did not show a significant difference in arterial hydrogen ion concentration (pH), plasma bicarbonate concentration (HCO3-), partial pressure of carbon dioxide (PCO2), plasma base excess (BE), or plasma ANP concentration. alpha-rANP infusion produced a continuous blood pressure reduction in both nephrectomized and control rats. Urine volume and urinary sodium and potassium excretion tended to increase at 2-hour infusion, but not at 12-hour infusion. In the controls alpha-rANP significantly increased pH from 7.47 to 7.50, and decreased PCO2 by 14%. In contrast, in nephrectomized rats alpha-rANP significantly decreased pH from 7.48 to 7.44, HCO3- by 13%, and BE from -0.07 to -3.22 meq/l. Rats with chronic renal failure had greater reduction in HCO3- than the controls (p less than 0.05). There was no difference in plasma ANP level between the two groups. Thus, it is indicated that the long-term infusion of alpha-rANP reduces pH in rats with chronic renal failure, thereby adversely affecting the acid-base balance.

Topics: Acid-Base Equilibrium; Animals; Atrial Natriuretic Factor; Blood Pressure; Creatinine; Diuresis; Heart Rate; Kidney Failure, Chronic; Male; Potassium; Rats; Sodium

The remnant kidney model of progressive renal failure in the rat was used to assess the relationships between the renin-angiotensin system, exchangeable body sodium, and both plasma concentration and atrial content of atrial natriuretic factor (ANF) measured sequentially over 4 weeks. Following subtotal nephrectomy plasma creatinine (mumol/L) rose from 40 +/- 6 (sham) to 107 +/- 24 (P less than 0.05) at 1 week, and rose further to 124 +/- 20 (P less than 0.05) by 4 weeks. Plasma renin activity (nanograms of angiotensin I/mL/min) rose from 4.5 +/- 0.5 to 11.8 +/- 2.8 (P less than 0.05) at 1 week, but was suppressed by 4 weeks to 2.2 +/- 0.3 (P less than 0.001). Plasma angiotensin II (pg/mL) was 52 +/- 2 (sham), 117 +/- 20 at 1 week (P less than 0.05) and 51.3 at 4 weeks. Exchangeable sodium (mmol/kg) rose progressively from 43.2 +/- 5 (before surgery) to 48.6 +/- 0.9 at 1 week and 50.8 +/- 2.2 at 4 weeks. Plasma atrial natriuretic factor (ANF) (pg/mL) rose progressively from 114 +/- 6 (sham) to 248 +/- 31 (P less than 0.01) at 1 week and 456 +/- 78 at 4 weeks (P less than 0.01). Atrial ANF content fell as the plasma concentration rose. In the remnant kidney model of progressive renal failure there was a progressive increase in exchangeable body sodium and plasma atrial natriuretic factor, with reciprocal changes in atrial ANF content suggesting that ANF secretion rate was increased. Initially the renin-angiotensin system was stimulated, but later it was suppressed.

Topics: Animals; Atrial Natriuretic Factor; Creatinine; Heart Atria; Kidney Failure, Chronic; Rats; Renin-Angiotensin System; Sodium

To investigate whether plasma atrial natriuretic peptide (ANP) is a valuable index to detect fluid expansion in children with endstage renal disease, we studied 34 children and adolescents on regular intermittent hemodialysis or on continuous ambulatory peritoneal dialysis (CAPD). In 22 pediatric patients, plasma ANP was markedly elevated prior to hemodialysis and fell to near normal levels after dialysis (109.9 +/- 80.0 to 39.0 +/- 23.1 fmol/ml, means +/- SD). During removal of fluid excess by 1-h sequential ultrafiltration without dialysis in eight adolescents, plasma ANP fell from 123.8 +/- 97.0 to 45.3 +/- 24.6 fmol/ml. Ultrafiltration was followed by 3 h hemodialysis with fluid removal and ANP decreased further to 29.6 +/- 12.1 fmol/ml. In 12 patients on CAPD, plasma ANP was similar to that in 96 healthy control children (29.3 +/- 28.9 vs 23.9 +/- 11.9 fmol/ml) and did not differ from that in 12 children with advanced chronic renal failure (32.6 +/- 20.1 fmol/ml) and seven successfully transplanted children (32.4 +/- 8.5 fmol/ml). Four patients on hemodialysis (post dialysis), one on patients on hemodialysis (post dialysis), one on CAPD and two with advanced chronic renal failure had definitely elevated ANP levels (greater than 56 fmol/ml = greater than 3 SD mean of controls) indicating fluid volume overload. It is concluded that plasma ANP is elevated in children with chronic renal failure due to volume expansion and that measurement of plasma ANP is a sensitive marker to detect fluid overload in these children.

Topics: Adolescent; Atrial Natriuretic Factor; Blood Pressure; Child; Hematocrit; Hemoglobins; Humans; Kidney Failure, Chronic; Peritoneal Dialysis, Continuous Ambulatory; Reference Values

The role of human atrial natriuretic peptide (alpha-hANP) in chronic blood pressure (BP) and extracellular fluid volume (ECFV) regulation remains elusive. Hence, the role of alpha-hANP in chronic renal failure is of particular interest since in this pathological condition: (1) increased sodium and water retention plays a major pathogenetic role in the development of hypertension and (2) altered secretion and/or metabolism of alpha-hANP may contribute to fluid volume and BP regulation. To evaluate the relationship between the degree of renal insufficiency, BP and circulating alpha-hANP, we determined plasma alpha-hANP concentrations by radioimmunoassay in 16 nondialyzed patients with progressive chronic renal failure (CRF) of various degrees; subsequently analysis of potential molecular heterogeneity of immunoreactive (ir) ANP was performed by means of gel permeation of plasma extracts from patients with CRF without concomitant hypertension. Serum creatinine concentrations ranged from 127 to 1187 (435 +/- 76) mumol/l, systolic BP from 135 to 200 (158 +/- 4) and diastolic BP from 80 to 110 (94 +/- 2) mmHg, respectively. Plasma alpha-hANP concentrations ranged from 5 to 75 (23 +/- 4) pmol/l which was thus significantly higher as compared to 9 +/- 2 pmol/l found in healthy volunteers (p less than 0.05). A highly significant linear correlation between plasma alpha-hANP and serum creatinine concentrations (r = 0.92; p less than 0.01) was observed; a weaker correlation was found between mean arterial pressure and alpha-hANP (r = 0.66) and serum creatinine concentration (r = 0.59), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Molecular Weight; Radioimmunoassay

Fluid overload is a frequent complication in anuric patients undergoing hemodialysis (HD) or hemofiltration (HF). Elevated ANP plasma concentrations are associated with overhydration or congestive heart failure (CHF). After intensive ultrafiltration in 18 HD patients with high ANP levels at the end of HD, ANP values normalized (28 +/- 4 fmol/ml) in 11 patients (group A), suggesting previous volume overload, whereas ANP remained elevated (126 +/- 31 fmol/ml) in seven patients (group B). Left ventricular ejection fraction by radionuclide ventriculography (LVEF) was significantly (p less than 0.01) lower in group B (41 +/- 7%) as compared to normal values in group A (67 +/- 8%). M-mode echocardiography demonstrated left atrial enlargement (53 +/- 3 mm) and pathologic enddiastolic left ventricular diameters (58 +/- 4 mm) in group B, compared to normal dimensions of left atrial (43 +/- 1 mm) and left ventricular enddiastolic diameters (47 +/- 4 mm) in group A. Persisting high ANP concentrations after intensive ultrafiltration in HD patients indicate CHF and require further diagnostic evaluation.

Topics: Atrial Natriuretic Factor; Blood Volume; Echocardiography; Female; Hemofiltration; Humans; Kidney Failure, Chronic; Male; Middle Aged; Radioimmunoassay; Renal Dialysis

Using RIAs for the N- and C-terminal fragments of the human atrial natriuretic polypeptide (ANP) precursor gamma ANP, that is gamma ANP-(1-25), and alpha ANP [gamma ANP-(99-126)], we studied the secretion of gamma ANP-derived peptides from the heart in normal subjects and patients with heart disease, chronic renal failure, and cirrhosis. We detected gamma ANP-(1-25)-like immunoreactivity (-LI) in plasma from normal subjects (n = 17) in considerable amounts [mean, 510 +/- 62 (+/- SE) pg/mL (174 +/- 21 pmol/L)]; the mean plasma alpha ANP-LI level at the same time in these subjects was 32.8 +/- 4.4 pg/mL (10.7 +/- 1.4 pmol/L). Gel permeation chromatographic analysis of plasma samples from normal subjects and patients with heart disease and chronic renal failure revealed two major components; one was alpha ANP, and the other was the 10K N-terminal gamma ANP fragment (N-peptide) resulting from the removal of alpha ANP (3K) from gamma ANP (13K). In addition, gamma ANP (13K), which possessed both gamma ANP-(1-25)-LI and alpha ANP-LI, and beta ANP, an antiparallel dimer of alpha ANP, were detected in some patients as minor components. A significant positive correlation between plasma levels of the N-terminal gamma ANP fragment and alpha ANP (P less than 0.01) and almost equal step-ups in the coronary sinus plasma levels of the N-terminal gamma ANP fragment and alpha ANP suggest that they are cosecreted in equimolar amounts. The high molar ratio of plasma gamma ANP-(1-25)-LI to alpha ANP-LI (17.4 +/- 1.4) in normal subjects and the significantly higher ratio in patients with chronic renal failure (36.9 +/- 7.1; P less than 0.01) suggest the slower clearance of the N-terminal gamma ANP fragment than alpha ANP and a role for the kidney in its degradation. Since the molar ratio of plasma gamma ANP-(1-25)-LI to alpha ANP-LI in patients with cirrhosis (20.7 +/- 2.7) was similar to that in normal subjects, it is unlikely that the N-terminal gamma ANP fragment is metabolized by the liver. In patients with heart disease, plasma gamma ANP-(1-25)-LI and alpha ANP-LI levels were higher in those with cardiac decompensation and were positively correlated with right atrial pressure, pulmonary arterial pressure, and pulmonary capillary wedge pressure, indicating cosecretion of the N-terminal gamma ANP fragment and alpha ANP in response to atrial stretch.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adult; Aged; Atrial Natriuretic Factor; Chromatography, Gel; Chromatography, High Pressure Liquid; Female; Heart Diseases; Humans; Kidney Failure, Chronic; Liver Cirrhosis; Male; Middle Aged; Peptide Fragments; Radioimmunoassay

1. In order to examine the potential role of endogenous atrial natriuretic peptide (ANP) in modulating the increased sodium excretion per nephron in chronic renal failure, we studied healthy subjects with normal renal function (group I) and patients with moderate (group II) or severe chronic renal failure (group III) before, during and after administration of an intravenous sodium load. All subjects had been on a controlled diet containing 120 mmol of sodium per day for 5 days before the study. 2. Under basal conditions, plasma ANP and fractional excretion of sodium (FENa) were highest in group III. Both parameters increased in response to the sodium load in the three groups studied (P less than 0.001). Changes with time differed from group to group (P less than 0.05), the more marked response for both parameters being observed in group III. After adjustment with respect to plasma ANP (analysis of covariance), FENa was no longer modified in response to the sodium load, whereas adjustment of FENa with respect to mean blood pressure was without consequence on the significance of its change with time. This demonstrates that plasma ANP, but not mean blood pressure, represents the main factor producing variation in FENa during and after the sodium load. 3. These results suggest an important role for plasma ANP in promoting adaptation of short-term sodium excretion in response to an acute sodium load in patients with chronic renal failure who ingest a normal sodium intake.

Topics: Adaptation, Physiological; Adult; Atrial Natriuretic Factor; Female; Humans; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Sodium

Topics: Atrial Natriuretic Factor; Humans; Kidney Failure, Chronic; Osmolar Concentration; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis

A highly sensitive radioimmunoassay to measure atrial natriuretic peptide (ANP) concentration in urine has been established, and its clinical usefulness is presented. ANP in urine was stable at 4 degrees C for several days and was easily measured by our radioimmunoassay. The average ANP excretion in 65 healthy persons was 25.0 +/- 1.4 ng/day (mean +/- SEM) and the fractional excretion of ANP was 0.7 +/- 0.05%. In 14 patients with congestive heart failure, the average ANP excretion was 119.2 +/- 29.4 ng/day, which decreased to 53.3 +/- 11.0 after successful treatment.

Topics: Adult; Aged; Atrial Natriuretic Factor; Digitalis Glycosides; Diuretics; Female; Heart Failure; Humans; Kidney Failure, Chronic; Male; Middle Aged; Radioimmunoassay

Sensitive radioimmunoassay for determination of immunoreactive atrial natriuretic peptide (ANP) in human plasma was developed and employed for the study of plasma ANP concentrations in healthy controls under basal conditions (2.4 +/- 0.1 pmol/l) and during volume expansion by saline infusion (9.6 +/- 2.0 pmol/l and 14.2 +/- 1.8 pmol/l, respectively). Plasma renin activity and plasma aldosterone concentration exhibited opposite changes during saline infusion. In pathological states associated with extracellular fluid volume (ECFV) expansion, ANP concentration were significantly higher than in the controls (liver cirrhosis 8.6 +/- 0.9; congestive heart failure 33.1 +/- 4.8; chronic renal failure before haemodialysis 72.2 +/- 6.4 pmol/l). Further volume expansion in liver cirrhosis by saline infusion led to the further increase in ANP (13.3 +/- 1.3 and 16.1 +/- 1.5 pmol/l, respectively) and ECFV reduction by ultrafiltration during haemodialysis in chronic renal failure diminished but did not normalize plasma ANP (22.5 +/- 2.9 pmol/l). In patients with arterial hypertension the concentration of ANP exceeded the normal range by 62.5% and reached 8.0 +/- 0.5 pmol/l on the average. Our results support the suggestion that ANP is an important regulatory humoral mechanism participating in the regulation of sodium, volume and blood pressure homeostasis.

Topics: Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Electrolytes; Extracellular Space; Heart Failure; Homeostasis; Humans; Hypertension; Kidney Failure, Chronic; Liver Cirrhosis; Radioimmunoassay; Renin; Water-Electrolyte Balance

Atrial natriuretic factor (ANF) levels were ten times normal in hemodialysis patients before dialysis. ANF was not cleared by the dialyzer membrane but plasma levels decreased 47% by the end of dialysis. Patients undergoing peritoneal dialysis had plasma ANF levels four times normal and had detectable ANF in their dialysate. Hemodialysis patients with a marked fall in BP after dialysis had higher ANF levels (P less than 0.05) and lower norepinephrine (NE) levels (P less than 0.05) associated with a failure to increase NE in response to dialysis. Elevated ANF levels are associated with postdialysis hypotension in hemodialysis patients.

Topics: Adult; Aged; Atrial Natriuretic Factor; Female; Humans; Hypotension, Orthostatic; Kidney Failure, Chronic; Male; Metanephrine; Middle Aged; Norepinephrine; Normetanephrine; Peritoneal Dialysis; Renal Dialysis

The possible role of atrial natriuretic peptides (ANP) for the adaptive changes in renal Na excretion during chronic renal failure was studied in 5/6 nephrectomized (NX) rats maintained on a normal (100 mmol/kg) and a high (800 mmol/kg) Na diet. Atrial content of natriuretic substances was determined by bioassay and plasma ANP by radioimmunoassay. Nephrectomized rats showed a twofold increase in plasma ANP irrespective of their Na intake. Atrial ANP content was increased by high Na diet but unchanged by NX. Nephrectomized rats maintained on high Na diet showed partial depletion of atrial ANP stores. There were no significant changes in the volume fraction of atrial granules determined. The results suggest that ANP is involved in the regulation of renal Na excretion during chronic renal failure and acute Na loading; other mechanisms are probably involved in the adaption to chronic Na loading.

Topics: Animals; Atrial Natriuretic Factor; Female; Heart Atria; Kidney Failure, Chronic; Male; Nephrectomy; Rats; Rats, Inbred Strains; Sodium; Urea

We measured plasma levels of immunoreactive human atrial natriuretic factor (ANF) in chronic renal failure patients treated by hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). Predialysis plasma ANF was significantly higher in HD patients (271.8 +/- 173.4 pg/ml) as compared to CAPD patients (81.8 +/- 80.5 pg/ml) and healthy subjects (31.5 +/- 19.8 pg/ml). Plasma volume was higher in HD patients than in CAPD patients. Plasma ANF and plasma volume showed a significant positive correlation. In HD patients, high plasma ANF value decreased significantly to a value comparable with that of CAPD patients after each dialysis. The removal rates of ANF by HD and CAPD were comparable. Ultrafiltration corresponding to 2% of body weight without dialysis also reduced plasma ANF. Thus, the difference in plasma ANF values between HD and CAPD patients seems to be mostly due to the difference in plasma volume, indicating that plasma ANF is sensitive to volume status even in chronic dialysis patients.

Topics: Adult; Atrial Natriuretic Factor; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Plasma Volume; Renal Dialysis

Basal plasma atrial natriuretic peptide (ANP) and blood pressure were measured in 11 patients with chronic renal failure before requirement of dialysis, 13 patients on chronic dialysis, and 28 control subjects (Study 1). Changes in ANP during noradrenaline infusion were determined in eight patients with chronic renal failure before dialysis, 12 patients on chronic dialysis, and 17 control subjects (Study 2). ANP was also measured in 14 healthy control subjects during angiotensin II infusion (Study 3). Study 1 showed a significantly greater ANP in patients before the stage of dialysis (median 23 pg/ml) and in dialysis patients (34 pg/ml) than in control subjects (19 pg/ml) P less than 0.01 for both. In Study 2, noradrenaline induced an increase in ANP in the non-dialysed patients (P less than 0.05) and in the control subjects (P less than 0.01), but not in the dialysis patients. According to Study 3, ANP was unchanged during angiotensin II infusion. Blood pressure was increased in all groups during noradrenaline and angiotensin II infusions. It can be concluded that ANP Is increased both in patients with chronic renal failure before requirement of dialysis and in patients on maintenance dialysis. It is suggested that noradrenaline stimulates ANP release.

Topics: Adolescent; Adult; Aged; Angiotensin II; Atrial Natriuretic Factor; Blood Pressure; Female; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Norepinephrine; Renal Dialysis

Echocardiographically determined left ventricular function and cardiovascular hormone balance were assessed before and after hemodialysis in 10 patients who had been on hemodialysis for 4 months to 15 years. Plasma levels of atrial natriuretic peptide (ANP), antidiuretic hormone (ADH), renin activity and aldosterone were determined. All patients had vector- and echocardiographic evidences of slight to moderate left ventricular hypertrophy. The body weight decreased 2.0 kg (3.3 +/- 0.5%) with dialysis. Nine out of ten patients showed a slightly reduced ejection fraction that normalized after dialysis (p less than 0.05). Left atrial and ventricular systolic dimensions were around the upper reference limit before dialysis with a decrease after dialysis (p less than 0.05 and p less than 0.02, respectively). The levels of ANP decreased with dialysis from 2-17 times to 1 to 15 times the upper reference value in nine out of the ten patients. In the whole group the decrease was 117 +/- 35% (p less than 0.005). A significant regression was obtained between percentage decrease of body weight and percentage change of ANP (r = 0.67; p less than 0.05). The plasma concentration of ADH did not change following dialysis but the mean value was significantly higher than the mean value of the reference group of the laboratory (p less than 0.05 before and p less than 0.005 after dialysis). Renin activity and aldosterone levels were low and did not change during dialysis. In conclusion, the slight left ventricular hypertrophy may partly be a response to volume overload with hyperdynamic circulation and partly to metabolically depressed myocardial function.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aldosterone; Atrial Natriuretic Factor; Cardiomegaly; Echocardiography; Female; Heart; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Renin; Vasopressins

The discovery of the atrial natriuretic factor (ANF) has opened a new field in modern biology. After rapid isolation and identification of this new peptide from atrial granules, it is now evident that this new hormone has a wide variety of actions with general implication in the control of vascular tone, sodium and water balance, hormonal secretion as well as neuronal functions. The major mode of action of this hormone is transmitted via its interaction with a membrane enzyme, particulate guanylate cyclase, leading to increases of cGMP levels. This nucleotide is a faithful marker of ANF action correlating with all functions ascribed to ANF up to date. Significant increases of ANF as well as of cGMP have been discovered in heart and renal failure, secondary hypertension and other states with altered salt-water balance, impairment of heart function and particularly increase of atrial pressure. The increases of levels and relative inefficiency of increased ANF have to be carefully interpreted in face of increased levels of cGMP. It can be expected that new pharmacological developments will occur in this area issuing from both our increasing knowledge concerning the peripheral mode of action of this hormone, its physiological implications as well as its pharmacological effectiveness in diseases with altered salt-water balance, cardiac function and blood pressure disregulation.

Topics: Atrial Natriuretic Factor; Cyclic GMP; Guanylate Cyclase; Heart Failure; Humans; Hypertension; Kidney Failure, Chronic; Metabolic Clearance Rate; Plasma Volume; Vasodilation; Water-Electrolyte Balance

Plasma levels of immunoreactive alpha human atrial natriuretic peptide (IR-ANP) were measured in nine patients with chronic renal failure before and after removal of 1.3-3.7 litres of fluid by ultrafiltration and again during volume repletion with intravenous sodium chloride solution (150 mmol/l: saline). Baseline levels of IR-ANP were elevated but fell by 22% during ultrafiltration. Saline infusion induced a rapid and steep rise in IR-ANP levels which were 150% of baseline while body weight was still 2% below baseline. Changes in plasma renin, angiotensin II, aldosterone and vasopressin during the study were slight compared with the change in IR-ANP, but noradrenaline levels rose threefold during ultrafiltration. There was a significant positive relationship between arterial pressure and IR-ANP levels before and after ultrafiltration. These results lend support to the suggestion that atrial peptides are of physiological importance, especially in states of chronic fluid overload such as chronic renal failure.

Topics: Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Blood Volume; Electrolytes; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Norepinephrine; Renin-Angiotensin System; Sodium Chloride; Ultrafiltration

Using direct radioimmunoassay, the plasma concentration of human atrial natriuretic polypeptide (hANP) was measured in patients with impaired renal function. Patients on maintenance hemodialysis (HD) and those still on medical management (non-HD) were examined. In 13 non-HD patients with serum creatinine values from 2.0 to 8.3 mg/dl, mean plasma hANP (+/- SE) was 404 +/- 23 pg/ml, while it was 236 +/- 11 pg/ml in the normal control group (n = 15) and the difference was significant (p less than 0.001). In all patients as a whole, there was a positive correlation between plasma hANP and mean blood pressure (r = 0.56, p less than 0.05) but no correlation was present between plasma hANP and renal function. Fifty-six HD patients were divided into 2 groups depending on blood pressure level. Plasma levels of hANP in the hypertensive (BP greater than or equal to 150/90 mmHg, n = 21) and in the normotensive (BP less than 150/90 mmHg, n = 35) HD group were 588 +/- 58 pg/ml and 364 +/- 29 pg/ml, respectively, with plasma hANP in both HD groups significantly higher than in the controls (p less than 0.001). There was also a significant difference of plasma hANP between hypertensive and normotensive HD patients (p less than 0.01). However, when the normotensive HD group without cardiomegaly (cardiothoracic ratio less than 50%, n = 17) was compared with the control, the value of plasma hANP was not statistically different from that of the control group. These results suggest that plasma hANP in patients with impaired renal function is influenced by blood pressure and/or cardiac condition.

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Female; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Radioimmunoassay; Renal Dialysis

In this simple, sensitive radioimmunoassay (RIA) of atrial natriuretic polypeptide (hANP) in human plasma, nonspecific interference is minimized by deproteinizing the plasma by heat treatment at 85 degrees C for 10 min. We directly measure alpha-hANP in the supernates by RIA, with use of antiserum that recognizes the N-terminal region of alpha-hANP. The minimal detectable value was 0.4 pg per tube. The intra-assay CV was 6.6% (n = 8). The mean concentration of hANP in plasma of 54 healthy volunteers was 41 (SD 29) ng/L. Concentrations of hANP in plasma increased after saline infusion and high salt intake for one week in patients with essential hypertension. High concentrations were also measured in patients with renal failure and congestive heart failure. This method, which requires no extraction or purification with column chromatography, is especially useful for simultaneous measurement of several samples.

Topics: Atrial Natriuretic Factor; Chromatography; Heart Failure; Hot Temperature; Humans; Hypertension; Kidney Failure, Chronic; Radioimmunoassay

A specific and sensitive radioimmunoassay has been developed and used to measure circulating atrial natriuretic peptide (ANP) in normal man and in patients with chronic renal failure. Circulating ANP levels rose with head-down tilt and exercise, and were raised in patients with chronic renal failure in proportion to volume status. This suggests that ANP release is mediated via increased atrial stretch, although other release mechanisms cannot be excluded. Extracts of normal human plasma subjected to reverse phase HPLC showed one major peak of immunoreactivity co-migrating with alpha-human ANP. However, when plasma extracts from patients with renal failure were chromatographed on a similar system, a second later eluting peak of ANP immunoreactivity was observed. This may represent circulating ANP precursors or degradation molecules. Significant arteriovenous differences in plasma ANP concentration were observed in patients with chronic renal failure. Arterial and venous plasma ANP levels decreased slightly after haemodialysis. Plasma ANP concentrations were inversely correlated with haematocrit in these patients.

Topics: Animals; Atrial Natriuretic Factor; Chromatography, High Pressure Liquid; Exercise Test; Humans; Kidney Failure, Chronic; Male; Posture; Radioimmunoassay; Rats; Renal Dialysis

The plasma concentration of atrial natriuretic peptide (ANP) in 16 healthy subjects on a free diet was 41 +/- 23 pg ml-1 (mean +/- SD) when upright and 58 +/- 27 pg ml-1 in the supine position (P less than 0.05), which confirms the concept that the supine position raises plasma ANP. Water immersion to the neck for 2 h caused a brisk diuresis, natriuresis and raised plasma ANP in 8 healthy subjects, suggesting that ANP is a mediator of diuresis and natriuresis during immersion. Dynamic exercise (50-200 W per 4 min) on a bicycle ergometer caused a gradual increase in plasma ANP in 6 healthy males, with a close correlation between the increases in plasma ANP and heart rate (r = 0.96). Thus, plasma ANP levels are increased in healthy subjects by stimuli causing an increased preload and possibly by tachycardia itself. Markedly raised plasma levels of ANP were found in patients with congestive heart failure, and upright posture caused a further rise of plasma ANP which correlated with the increase in heart rate (r = 0.87). High plasma ANP concentrations were also found in 25 patients with end-stage renal failure maintained on haemodialysis. When these patients were subdivided into those with concomitant heart failure and those with normal cardiac function, changes in plasma ANP correlated with predialysis weight gain and weight loss during dialysis, but only in patients without heart failure. In 9 infants treated by operative or pharmacological closure of persistent ductus arteriosus, high pre-treatment plasma ANP values were lowered by successful therapy, and plasma ANP correlated with the degree of left atrial distension.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Atrial Natriuretic Factor; Ductus Arteriosus, Patent; Female; Heart Failure; Humans; Immersion; Infant; Infant, Newborn; Kidney Failure, Chronic; Male; Physical Exertion

Plasma atrial natriuretic peptide (ANP) concentrations were measured by both direct radio-immunoassay and with pre-extraction of the peptide from plasma using C18 reverse phase columns. Peptide concentrations were measured in normal subjects (including a group of eight volunteers who received an intravenous infusion of 0.9% NaCl solution), patients with renal failure (including a group with end-stage disease undergoing renal dialysis) and patients with a spectrum of cardiac dysfunction. The overall correlation of results from direct and extracted assay methods was good. However, absolute values from extracted assays were significantly lower than from parallel direct assays. This discrepancy was due to interference from platelets and from another, as yet unidentified, plasma component demonstrated by gel filtration experiments. Extraction of the peptide from plasma by C18 columns largely eliminated these sources of interference and was particularly important for accurate measurement of peptide concentrations within the normal range. Plasma peptide concentrations were elevated in cardiac and renal failure, fell with renal dialysis and rose in normal subjects challenged with an intravenous isotonic fluid load. These findings suggest that ANP participates in the regulation of body fluid volumes and arterial pressure.

Topics: Adolescent; Adult; Atrial Natriuretic Factor; Buffers; Chromatography, Gel; Chromatography, High Pressure Liquid; Female; Heart Diseases; Humans; Kidney Failure, Chronic; Male; Middle Aged; Radioimmunoassay

We have used a sensitive direct radioimmunoassay to study the effects of exercise on plasma atrial natriuretic peptide (ANP) concentrations in man. Plasma ANP concentration increased three-fold in sixteen patients undergoing bicycle ergometer electrocardiographic tests for the investigation of chest pain. Resting ANP concentrations were higher in those patients in whom there was more evidence of heart disease, such as a positive exercise test, treatment with a beta blocker or history of myocardial infarction, although exercise resulted in increased ANP in both groups. We also confirm the increased plasma ANP concentration observed in patients with congestive cardiac failure and renal failure. In nine patients with renal failure routine haemodialysis was accompanied by a 30 per cent reduction in plasma ANP concentration. Plasma ANP concentrations were similar in treated hypertensive patients, untreated borderline hypertensive patients and normotensive subjects.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Electrocardiography; Exercise Test; Female; Heart Failure; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Physical Exertion; Radioimmunoassay; Renal Dialysis

In an attempt to clarify the clinical significance of atrial natriuretic peptide (ANP) in man, plasma levels of immunoreactive ANP were studied in patients with heart diseases and in those with chronic renal failure. When ANP concentrations in pulmonary arterial plasma were compared with hemodynamic variables in patients with heart diseases who underwent cardiac catheterization, a significant positive correlation was found between plasma ANP levels and mean pulmonary capillary wedge pressure, while plasma ANP levels were not significantly correlated to mean right atrial pressure (MRAP). After the injection of contrast medium, both MRAP and plasma ANP levels increased and a significant positive correlation was observed between two variables. Plasma levels of ANP were elevated in patients with congestive heart failure according to the severity. In addition, patients associated with atrial fibrillation showed significantly higher plasma ANP levels than those on sinus rhythm. In patients with paroxysmal atrial arrhythmias, plasma ANP levels increased markedly during paroxysms. Patients with chronic renal failure had elevated plasma ANP levels, which fell after hemodialysis. These results suggest that both left and right atrial tissue can secrete ANP as a result of stretching of the cardiocytes in man and that plasma ANP levels are elevated in patients with congestive heart failure and in those with chronic renal failure by increased atrial pressure due to volume expansion. Abnormal atrial contraction per se, in addition, may stimulate ANP secretion.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Atrial Natriuretic Factor; Cardiac Catheterization; Female; Heart Diseases; Heart Failure; Humans; Kidney Failure, Chronic; Male; Middle Aged; Pulmonary Wedge Pressure; Renal Dialysis

A monoclonal antibody (mab) directed against alpha-human atrial natriuretic peptides (alpha-hANP) was produced. Using this mab a radioimmunoassay for the determination of hANP-like immunoreactivity in human plasma was established. To demonstrate the possible application of this radioimmunoassay for clinical diagnosis, plasma levels were measured in healthy subjects and in patients with renal failure before and after hemofiltration or hemodialysis. Plasma levels in healthy subjects ranged between less than 30 and 124 pg/ml. Mean plasma concentrations of hANP-IR in uremic subjects were 324 pg/ml before and 113 pg/ml after hemofiltration or hemodialysis.

Topics: Adult; Aged; Antibodies, Monoclonal; Atrial Natriuretic Factor; Blood; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Radioimmunoassay; Renal Dialysis; Ultrafiltration

To study the effects of volume overload and renal failure on plasma levels of immunoreactive atrial natriuretic hormone (IR-ANH), we measured levels of this hormone in normal subjects, in patients with advanced chronic renal failure (CRF) with and without clinically evident volume overload, and in patients with end-stage renal disease (ESRD) treated with chronic hemodialysis. The levels were 13 +/- 2 pmol/l in normal volunteers, 77 +/- 24 pmol/l in patients with CRF without volume overload, and 219 +/- 50 pmol/l in patients with CRF and clinically evident volume overload (analysis of variance, p less than 0.001, alpha = 0.05 compared to normals). In patients with ESRD, the levels of IR-ANH were 145 +/- 46 pmol/l before dialysis and decreased to 87 +/- 31 after dialysis (p less than 0.025). No correlation was found between the decrease in IR-ANH levels and the decrease in weight during dialysis. A significant positive correlation was found between the IR-ANH levels and blood urea nitrogen in patients with CRF (r = 0.658, p less than 0.01). Volume overload appears to be the most important stimulatory factor for ANH secretion in renal failure patients but other mechanisms, especially a decrease in metabolic clearance, may also contribute to elevated plasma levels. The increased secretion of ANH in patients with renal failure may be an important adaptive response to volume overload and hypertension.

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Female; Heart Rate; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

Atrial natriuretic factor, plasma renin activity, and plasma vasopressin were measured in 38 patients with chronic renal failure prior to and after hemodialysis. The objective of the study was to evaluate the effect of acute volume changes on the level of atrial natriuretic factor. Blood pressure prior to dialysis was 154 +/-/83 +/- mmHg, and 132 +/-/78 +/- mmHg post dialysis (p less than 0.005) while heart rate increased from 82.5 +/- 1.8 beats per minute to 91.2 +/- 2.4 after dialysis (p less than 0.005). The average weight of patients was reduced from 60.2 +/- 2.4 kg to 57.8 +/- 2.4 kg (p less than 0.005). While the plasma levels of atrial natriuretic factor in normal individuals were 65.3 +/- 2.9 pg/ml (n = 59), these levels were 251.4 +/- 28 pg/ml prior to dialysis in the patients with renal failure, and 173.3 +/- 18.0 pg/ml after dialysis (p less than 0.005). Twenty-nine patients had a reduction in the levels of this atrial natriuretic factor, 5 had no change, and 4 had an increase. The atrial factor was not detected in the dialysate fluid of 6 patients in whom it was measured. Peripheral renin values were unchanged from 2.12 +/- 0.68 to 2.07 +/- 0.8 ng/ml/hr. Plasma vasopressin before dialysis was significantly higher than normal, and increased from 7.04 +/- 0.56 to 9.95 +/- 1.55 pg/ml following dialysis (p less than 0.05). The changes in atrial natriuretic factor values correlated most significantly (r = 0.47, p less than 0.005) with the changes in weight, but no single variable could explain the changes in atrial natriuretic factor.

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Pulse; Renal Dialysis; Renin; Vasopressins

1. Plasma concentration and atrial content of atrial natriuretic factor (ANF) were measured in rats with chronic renal failure induced by subtotal nephrectomy. 2. Plasma ANF was higher, and atrial ANF content lower in rats with renal failure when compared with sham-operated controls. 3. Plasma renin activity (PRA) and ANF were elevated at 1 week following subtotal nephrectomy. After 1 month plasma ANF had risen further, but PRA was suppressed to below control values. 4. Plasma ANF was also measured in six patients with chronic renal failure undergoing routine haemodialysis. 5. Elevated plasma ANF levels in patients with renal failure were lowered by haemodialysis, although extraction of ANF across the dialysis membrane was negligible. 6. Secretion of ANF is increased in chronic renal failure in man and the rat, possibly mediated by increased intravascular volume.

Topics: Animals; Atrial Natriuretic Factor; Body Weight; Creatinine; Hematocrit; Humans; Kidney Failure, Chronic; Male; Nephrectomy; Rats; Rats, Inbred Strains; Renal Dialysis; Renin; Renin-Angiotensin System

Plasma atrial natriuretic peptide (ANP) was measured by radioimmunoassay in 10 patients with end-stage renal failure during two successive 150-min periods of ultrafiltration and perfusion of an identical fluid volume (1,800-2,400 ml). The patients were divided into two groups of 'denervated' and 'intact' patients based on three different tests for cardiac parasympathetic dysfunction. Plasma ANP was higher in the denervated group than in the intact group throughout all the study, but decreased with the volume ultrafiltered and increased with the volume perfused in both groups. The sensitivity of ANP response to perfusion was greater in denervated than in intact patients. These results demonstrate the close relationship between plasma ANP and stepwise decremental or incremental changes in extracellular fluid volume. They also suggest that cardiac parasympathetic innervation plays a role in modulation of ANP secretion in humans.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Extracellular Space; Female; Heart; Humans; Kidney Failure, Chronic; Male; Middle Aged; Parasympathetic Nervous System; Plasma Volume; Ultrafiltration; Uremia

A synthetic atrial natriuretic peptide (ANF) has been administered to 7 patients with chronic renal failure to evaluate the role of ANF in the regulation of blood volume. ANF (2 micrograms/min) was infused for 60 minutes before hemodialysis and blood pressure, heart rate, plasma proteins and hematocrit were measured at regular intervals. Although a slight decrease in blood pressure occurred during ANF infusion, no significant changes in hematocrit and plasma proteins were observed. These results suggest that administration of exogenous ANF does not modify the volume distribution in patients with chronic renal failure. ANF's lack of effect is perhaps due to the chronic hypervolemia and the high plasma levels of endogenous ANF commonly found in these patients.

Topics: Aged; Atrial Natriuretic Factor; Blood Pressure; Blood Proteins; Blood Volume; Female; Heart Rate; Hematocrit; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

Plasma immunoreactive atrial natriuretic peptide (irANP) levels, their chromatographic profile, relationship with hemodynamic variables, and responses to hemodialysis (HD) or postural changes were investigated in HD patients. Peripheral venous supine plasma irANP averaged 167 +/- 31 (+/- SEM) pg/ml in 12 normal subjects (age 63 +/- 2 yr). In 42 HD patients (mean age 65 +/- 1 yr), plasma irANP in peripheral arterio-venous fistulae was high (447 +/- 50 pg/ml, P less than 0.01) before HD and decreased (P less than 0.001) to 164 +/- 24 pg/ml after HD. The latter reduced body weight by -2.3 +/- 0.2 kg (P less than 0.001) and blood pressure from 139/77 +/- 4/2 to 126/73 +/- 4/2 mm Hg (P less than 0.01). Pre-dialysis plasma irANP in right atrium, pulmonary artery or avfistula correlated with pulmonary capillary wedge pressure (N = 10, r = 0.66 to 0.73; P less than 0.05); HD-induced changes in these variables were also correlated (r = 0.80 to 0.90; P less than 0.05 to less than 0.01). Compared with supine values, upright posture decreased plasma irANP in 12 normal subjects and 8 HD patients (-40 and -42%, respectively, P less than 0.01). IrANP clearance from plasma averaged 24 +/- 5 ml/min across the hemodialyzer (N = 6) and 46 +/- 3 ml/min across the hemofilter (N = 4). We conclude that in terminal renal failure, circulating irANP consists largely of alpha ANP, is often elevated before HD, decreases with the change from recumbency to standing, falls after removal of excess fluid, and may depend strongly on left atrial and pulmonary arterial pressures.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Age Factors; Aged; Atrial Natriuretic Factor; Blood Pressure; Female; Hemodynamics; Humans; Kidney Failure, Chronic; Male; Posture; Pulmonary Wedge Pressure; Renal Dialysis

Topics: Atrial Natriuretic Factor; Edema; Heart Failure; Humans; Kidney Failure, Chronic; Liver Cirrhosis

Topics: Animals; Atrial Natriuretic Factor; Chemical Phenomena; Chemistry; Dogs; Heart Atria; Heart Failure; Humans; Hypertension; Kidney Failure, Chronic; Rats; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface

A RIA for alpha-human atrial natriuretic peptide (alpha hANP) in plasma was developed and used to study the immunoreactive components secreted by the heart and circulating in peripheral venous plasma. The assay used [125I]diiodotyrosyl-alpha hANP, purified by high pressure liquid chromatography (HPLC), and a C-terminal-specific antiserum purchased from Peninsula Laboratories. Serial dilution curves of coronary sinus plasma samples were parallel with the standard curve, but significant nonparallelism was found in peripheral plasma samples of low immunoreactivity. When plasma was extracted using C-18 Sep-Pak cartridges, serial dilution curves from both coronary sinus and peripheral plasma samples were parallel to the standard curve. Although values for plasma samples assayed before and after extraction agreed closely (r = 0.99; n = 76), immunoreactive ANP in unextracted plasma was consistently greater (70-79 pmol/liter) than in extracts of plasma, suggesting non-specific interference by a component in plasma when assayed without extraction. Mean plasma immunoreactive ANP in 19 normal subjects consuming a normal salt intake was 14 +/- 1 (+/- SE) pmol/liter. In 5 normal men, increasing dietary sodium intake from 10 to 200 mmol sodium/day was associated with a 2-fold increment in ANP levels, and similar changes accompanied acute sodium loading using iv saline. Elevated values were found in patients with congestive heart failure (mean, 58 pmol/liter; range, 0-200; n = 9), chronic renal failure (mean, 118 pmol/liter; range, 30-290; n = 8), and primary aldosteronism (range, 32-90 pmol/liter; n = 3). HPLC and gel chromatographic analysis of the immunoreactive material found in coronary sinus plasma extracts showed that a large amount of the material eluted in the position of alpha hANP. A smaller quantity of immunoreactive material with a mol wt of about 1600 was also identified. Peripheral venous plasma extracts also contained several immunoreactive components, the largest amount of which corresponded to alpha hANP. The pattern of immunoreactive components in peripheral venous plasma, as identified by both gel chromotography and HPLC, was similar to that in coronary sinus plasma drawn during an active phase of hormone secretion. These findings indicate that the heart secretes alpha hANP or a closely similar peptide which is also present in peripheral venous plasma. Plasma immunoreactive ANP is responsive to sodium loading in normal man and is elevated in patients

Topics: Adult; Atrial Natriuretic Factor; Chromatography, Gel; Chromatography, High Pressure Liquid; Female; Heart Failure; Humans; Hyperaldosteronism; Iodine Radioisotopes; Isotope Labeling; Kidney Failure, Chronic; Male; Middle Aged; Radioimmunoassay; Sodium; Specimen Handling

Plasma immunoreactive human atrial natriuretic peptide (Ir-ANP) levels were measured in eight patients with chronic renal failure who were volume-expanded and during treatment by sequential ultrafiltration and haemodialysis. One patient was studied at two separate treatment sessions. Plasma Ir-ANP levels were raised in all patients (mean +/- SE 184 +/- 44 pmol/l, n = 9) compared with healthy controls (11 +/- 1.4 pmol/l), but showed considerable inter-patient variability. Plasma Ir-ANP levels fell with fluid removal during ultrafiltration (123 +/- 30 pmol/l, n = 9, P less than 0.02) and again as fluid was removed during haemodialysis (76 +/- 20 pmol/l, n = 9, P less than 0.02). Seven patients studied 48 h later, before their next dialysis treatment, had regained weight and showed a coincident rise in circulating plasma Ir-ANP (130 +/- 33 pmol/l, n = 7). Our data would support the hypothesis that the secretion of ANP is determined by volume or by a stimulus related to volume. However, it does not exclude the possibility that a factor other than extracellular fluid volume expansion contributes to the raised plasma Ir-ANP levels in chronic renal failure.

Topics: Adult; Arginine Vasopressin; Atrial Natriuretic Factor; Blood; Blood Pressure; Blood Urea Nitrogen; Body Weight; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Osmolar Concentration; Potassium; Radioimmunoassay; Renal Dialysis; Sodium; Ultrafiltration

Sprague-Dawley rats given bolus intravenous injections of vasoconstrictors, including 1-deamino-Arg8-vasopressin (dAVP), demonstrated remarkable increases in plasma immunoreactivity (APir) to atriopeptin (AP). These elevations were accompanied by increases in systemic blood pressure, right atrial pressure and urinary volume excretion. Fractionated plasma APir peaks obtained by stimulation with dAVP were identified as primarily AP 28, with a smaller amount of AP 24, suggesting that AP 28 is the predominant circulating atrial peptide. Rats with reduced renal mass have increased single-nephron glomerular filtration rates (GFR). Despite these increases, AP 24 stimulated a marked increase in total GFR and promoted a profound natriuresis and diuresis. Atriopeptin 24 may therefore have potential as a therapeutic tool in the management of volume overload in chronic renal failure.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Glomerular Filtration Rate; Kidney Failure, Chronic; Natriuresis; Peptide Fragments; Rats; Rats, Inbred Strains; Stimulation, Chemical; Vasoconstrictor Agents

Radio-immunoassay of atrial natriuretic peptide (ANP) and infusions of alpha-human ANP (alpha-hANP) have been used to study the secretion, metabolism, regulation and actions of ANP in man. Plasma immunoreactive ANP (irANP) was twice as high in arterial blood as in simultaneously sampled venous plasma from the femoral, hepatic and renal vein, but no arteriovenous difference was found across the lung. Analysis of plasma extracts by high performance liquid chromatography confirmed that alpha-hANP-like material was a major component in coronary sinus and peripheral arterial and venous plasma. In normal subjects, venous plasma irANP was increased by both acute and chronic sodium loads, and by exercise. The cardiac secretion of irANP, and peripheral venous levels, were markedly increased by atrial pacing in four patients investigated for arrhythmia. Plasma irANP concentrations were elevated in many patients with circulatory disorders, including chronic renal failure, congestive heart failure and during spontaneous tachyarrhythmias. Constant 60-min intravenous infusions of alpha-hANP increased urinary sodium excretion in normal subjects, under conditions of both high- and low-sodium intake, and selectively reduced plasma aldosterone concentrations. These effects were observed at the venous levels of plasma irANP found in some patients with circulatory disease. Taken together, the present studies suggest that ANP has important endocrine functions in human health and disease.

Topics: Aldosterone; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Cardiac Pacing, Artificial; Chromatography, High Pressure Liquid; Female; Heart Failure; Humans; Hyperaldosteronism; Kidney Failure, Chronic; Natriuresis; Physical Exertion; Pregnancy; Radioimmunoassay

To examine the physiological role of atrial natriuretic factor (ANF) in the maintenance of sodium homeostasis under various conditions, we performed experiments in rats across a wide range of sodium intake, in rats with chronic renal insufficiency at extremes of sodium intake, and in rats given desoxycorticosterone acetate. After three weeks of a very low sodium diet, regular diet, or regular diet plus 1% saline as drinking water, no difference in plasma values of immunoreactive atrial natriuretic factor (IR-ANF) were identified, while rats at the lowest level of sodium intake had elevated atrial values. Normal rats, and rats with 5/6 nephrectomy has plasma values of IR-ANF which were no different irrespective of their sodium intake, nor were atrial values in these rats different. Although mineralocorticoid "escape" could be documented by changes in urine sodium excretion, neither plasma nor atrial IR-ANF values showed differences either at 24 or 72 hr after "escape". The data are consistent with previous observations that ANF serves the purpose of affecting rapid adjustments to large alterations in circulating fluid volume. Chronic high sodium intake, adaptation to renal insufficiency, and adjustment to the effect of mineralocorticoid do not appear to be associated with increased circulating plasma concentrations of IR-ANF.

Topics: Animals; Atrial Natriuretic Factor; Desoxycorticosterone; Diet, Sodium-Restricted; Dose-Response Relationship, Drug; Kidney Failure, Chronic; Male; Natriuresis; Nephrectomy; Rats; Rats, Inbred Strains; Sodium; Sodium Chloride; Water-Electrolyte Balance

Plasma levels of atrial natriuretic peptide (ANP) were measured in 57 patients with chronic renal failure (CRF) using a specific and sensitive RIA. The mean plasma ANP level in CRF patients [173 +/- 17.0 pg/ml (+/- SEM); n = 57] was significantly higher than that in normal subjects (37.6 +/- 1.9 pg/ml; n = 40). No significant correlation was found between plasma ANP and serum creatinine concentrations. CRF patients treated by maintenance hemodialysis had significantly higher plasma ANP levels than did nondialysis patients. Hemodialysis significantly decreased plasma ANP, and changes in plasma ANP levels after hemodialysis differed from those in serum creatinine concentrations. The mean serum creatinine concentration rose significantly 24 h after hemodialysis. In contrast, plasma ANP levels did not change in the first 24 h, but then rapidly increased. When ANP in predialysis plasma from patients with CRF was analyzed by reverse phase high performance liquid chromatography, the retention time of the main ANP peak coincided with that of synthetic human alpha ANP. These results suggest that expanded extracellular volume stimulates the secretion of ANP in CRF patients and that this increase in ANP release reflects a mechanism of compensation in volume homeostasis in man.

Topics: Adult; Aged; Atrial Natriuretic Factor; Chromatography, High Pressure Liquid; Creatinine; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

Twenty patients with chronic renal failure were studied before and after haemodialysis. Plasma atrial natriuretic peptide (ANP) concentrations were markedly elevated (P less than 0.01) before dialysis in comparison with healthy control subjects. After haemodialysis the plasma ANP concentration was lower in 19 patients (P less than 0.01) but remained above the normal range in all but three cases. Systolic and diastolic blood pressure and body weight fell during dialysis but none of these changes correlated with the reduction of the plasma ANP concentration. Chromatographic analysis of plasma extracts indicated that alpha-ANP is the predominant circulating molecular form. The increase in concentration of ANP in plasma between dialyses, at a time when many patients are susceptible to sodium and water overload, and its return towards normal after dialysis supports the putative role of ANP as a circulating factor released in response to sodium and water accumulation.

Topics: Adolescent; Adult; Aged; Atrial Natriuretic Factor; Chromatography, Gel; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

The effect of volume changes on the plasma concentration of atrial natriuretic peptide (ANP) was investigated. In children with chronic renal failure predialysis plasma ANP was higher as compared to normal children and decreased significantly during hemodialysis. The decrease in plasma ANP correlated with body weight reduction. On the other hand, increase in plasma volume by infusion of albumin in children with nephrotic syndrome caused significant rise in plasma ANP and an increased natriuresis. Our data demonstrate that an expanded extracellular fluid volume and/or plasma volume appears to be a major stimulus for the release in ANP in children.

Topics: Adolescent; Albumins; Atrial Natriuretic Factor; Blood Volume; Child; Child, Preschool; Extracellular Space; Female; Humans; Kidney Failure, Chronic; Male; Natriuresis; Nephrotic Syndrome; Renal Dialysis

Twenty-five years after the discoveries of the existence of atrial granules and of volume receptors in the heart atria the search for natriuretic hormones has led to the isolation and identification of the atrial natriuretic factors (ANF) now considered as a hormonal system. These peptides are probably synthesized and stored in the Golgi apparatus of cardiac myocytes and are released in response to atrial wall stretch following acute plasma volume expansion and increased central blood volume, e.g., during head-out water immersion, in arterial hypertension, or increased left and/or right atrial pressure in cardiac failure, but also possibly in response to increased frequency of myocardial contractions, e.g. in paroxysmal tachycardia. The mechanisms of the renal action of these potent natriuretic hormones are not yet precisely known. Increased GFR may contribute to the initial rise in urinary sodium excretion and increased renal medullary blood flow to the later phase of natriuresis. The proximal tubule, the thin descending and the ascending limb of Henle's loop and especially the medullary collecting tubule were so far incriminated as tubular sites of action of ANF. Finally, recycling of sodium in medullary tissue and secretion of sodium via back-flux from the interstitium into the medullary collecting tubule are postulated to result in the hypernatric urine observed after ANF administration. Direct suppression of the secretion of renin, aldosterone, vasopressin, and vasopressin-stimulated cAMP synthesis may also contribute to its diuretic, natriuretic, and antihypertensive effects. The renal hemodynamic and tubular as well as the adrenal and systemic vascular effects are related to enhanced cGMP synthesis in medium-sized arterial vessels, in glomeruli and specific tubular segments, and in adrenal tissue, and may be calcium dependent. Specific ANF-binding sites were detected in these target organs. Although increased ANF release was observed in response to atrial distension in various disease states, which may contribute to renal sodium elimination in human hypertension and congestive heart failure, further studies are needed to identify its precise physiological and pathophysiological significance.

Topics: Amino Acid Sequence; Animals; Atrial Natriuretic Factor; Blood Volume; Glomerular Filtration Rate; Heart Atria; Heart Failure; Hemodynamics; Humans; Hypertension; Kidney Failure, Chronic; Kidney Tubules; Pressoreceptors; Renal Circulation; Renin-Angiotensin System; Sodium; Water-Electrolyte Balance

Circulating amounts of human atrial natriuretic peptide (hANP) are elevated in congestive heart failure and renal failure. Stretching of cardiac atria, due to volume expansion associated with these diseases, is widely accepted to be the predominant stimulus for release of the hormone. Measurements of hemodynamic parameters as well as plasma concentrations of ANP in the right cardiac atrium, pulmonary artery, radial artery and vena cava superior, before and after continuous veno-venous hemofiltration (CVVH) of critically ill volume expanded patients, proved that ANP might be a useful indicator of fluid balance in these patients.

Topics: Atrial Natriuretic Factor; Blood; Heart Failure; Humans; Kidney Failure, Chronic; Ultrafiltration; Water-Electrolyte Imbalance

There are no reliable parameters for the detection of fluid overload in anuric patients. In 70 patients on regular haemodialysis (HD) or haemofiltration (HF) treatment, plasma ANP IR concentrations were determined by radioimmunoassay and compared to 43 controls with normal renal function. ANP IR levels were markedly elevated immediately before HD or HF (m 82 fmol/ml) compared to ANP IR plasma concentrations after HD or HF (m 42 fmol/ml) and to ANP IR levels of healthy controls (m 19 fmol/ml). ANP IR was detected in haemofiltrates and found to be eliminated by HF. During isovolemic HF, ANP IR levels remained constant suggesting that ANP synthesis is much higher than elimination by HF and that the decrease in circulating volume at the end of HF or HD is the main stimulus for a lower secretion rate of ANP. Elevated ANP IR levels at the end of HD/HF were found to be associated with fluid overload even without clinical or radiographic symptoms. Consistent weight reduction was followed by a decrease of ANP IR levels.

Topics: Adolescent; Adult; Aged; Atrial Natriuretic Factor; Body Weight; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Radioimmunoassay; Renal Dialysis; Ultrafiltration; Water-Electrolyte Imbalance

A new method was applied to isolate a polypeptide hormone from human blood. The polypeptides from 1,000 1 of hemofiltrate with a molecular weight lower than 20 kDaltons were adsorbed to 2.5 kg alginic acid, then eluted, precipitated, and desalted on a G-25 Sephadex column, thus obtaining a crude lyophilised plasma polypeptide extract. These polypeptides were further submitted to ion-exchange chromatography. Thereafter, two steps of HPLC were carried out to purify a distinct polypeptide which was the circulating form of cardiodilatin (CDD) in this case. The amino acid analysis, C-terminal enzymatic cleavage by carboxypeptidase A, and sequence analysis showed that the only form of circulating cardiodilatin is the 28 amino acid residue containing molecule, cardiodilatin-99-126 cleaved from the C-terminus of cardiodilatin-126 and identical with alpha-ANP (alpha atrial natriuretic polypeptide). Other bioactive molecular forms of the polypeptide hormones of the cardiodilatin family were not detected in the hemofiltrate. The isolation procedure was followed up by a bioassay using in vitro vascular smooth muscle relaxation.

Topics: Amino Acid Sequence; Atrial Natriuretic Factor; Chromatography, High Pressure Liquid; Humans; Kidney Failure, Chronic; Molecular Weight; Muscle Proteins; Peptide Termination Factors

Topics: Animals; Atrial Natriuretic Factor; Fluorescent Antibody Technique; Heart Atria; Kidney Failure, Chronic; Kidney Glomerulus; Male; Rats; Rats, Inbred Strains; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface

The effect of volume changes on the plasma concentration of atrial natriuretic peptide (ANP) in children with chronic renal failure was investigated by the use of a specific and sensitive radioimmunoassay. Predialysis plasma ANP was significantly higher in children with end-stage renal disease than in healthy children and children with advanced renal failure without evidence of volume expansion. During haemodialysis plasma ANP decreased significantly and plasma renin activity rose slightly, whereas plasma arginine vasopressin and aldosterone did not change. Plasma ANP correlated positively with volume status (body weight gain during the interval between two haemodialysis sessions). An expanded extracellular fluid volume thus seems to be a major stimulus for the rise in ANP in children with end-stage renal disease. The findings suggest that ANP may be important in volume homoeostasis.

Topics: Adolescent; Atrial Natriuretic Factor; Body Weight; Child; Diuresis; Female; Humans; Kidney Failure, Chronic; Male; Muscle Proteins; Osmolar Concentration; Plasma Volume; Renal Dialysis

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

Chronic renal failure is frequently associated with volume overload, resulting in hypertension and, in some cases, congestive heart failure. Atriopeptin III (AP III), a 24-amino acid atrial peptide, is a potent vasodilator and natriuretic/diuretic agent in normal rats. An infusion of AP III at 0.2 microgram/kg per min for 60 min produced dramatic responses in animals with chronic renal failure (5/6 nephrectomy 4 wk before study). Systemic blood pressure fell 20% by the end of infusion. A pronounced rise in glomerular filtration rate (24%) was maintained during the infusion period when urine flow rate was stable (35-60 min), even though renal blood flow was unchanged from base line. Urinary volume increased 4.4-fold and sodium excretion increased 9 to 12-fold during the infusion. Fractional excretion of sodium ranged between 9 and 15% in those animals whose initial GFR values were lower than 0.5 ml/min. We conclude that AP III is a potent natriuretic/diuretic agent in rats with reduced renal mass, presumably exerting that effect predominantly through increases in GFR. This agent may well be useful in the treatment of volume overload in patients with chronic renal failure.

Topics: Animals; Atrial Natriuretic Factor; Disease Models, Animal; Diuresis; Glomerular Filtration Rate; Hypertension; Kidney; Kidney Failure, Chronic; Natriuresis; Nephrectomy; Rats; Regional Blood Flow