atrial-natriuretic-factor and Kidney-Diseases

Corin is a transmembrane protease that activates atrial natriuretic peptide (ANP), an important hormone in regulating salt-water balance and blood pressure. This review focuses on the regulation of corin function and potential roles of corin defects in hypertensive, heart, and renal diseases.. Proprotein convertase subtilisin/kexin-6 has been identified as a primary enzyme that converts zymogen corin to an active protease. Genetic variants that impair corin intracellular trafficking, cell surface expression, and zymogen activation have been found in patients with hypertension, cardiac hypertrophy, and pre-eclampsia. Reduced corin expression has been detected in animal models of cardiomyopathies and in human failing hearts. Low levels of circulating soluble corin have been reported in patients with heart disease and stroke. Corin, ANP and natriuretic peptide receptor-A mRNAs, and proteins have been colocalized in human renal segments, suggesting a corin-ANP autocrine function in the kidney.. Corin is a key enzyme in the natriuretic peptide system. The latest findings indicate that corin-mediated ANP production may act in a tissue-specific manner to regulate cardiovascular and renal function. Corin defects may contribute to major diseases such as hypertension, heart failure, pre-eclampsia, and kidney disease.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Female; Heart Diseases; Humans; Hypertension; Kidney; Kidney Diseases; Pre-Eclampsia; Pregnancy; Proprotein Convertases; Receptors, Atrial Natriuretic Factor; Serine Endopeptidases

Blood pressure control is regulated by complicated physiological mechanisms, which are dependent upon cardio-vascular, neurological, endocrine systems and the kidneys. The kidneys plays an important role in the regulation of blood pressure based on sodium and water balance, renin-an. giotensin-aldosterone axis, sympathetic activity as well as other regulatory substances like: natriuretic peptides (ANP, BNP) endothelin, dopamine, prostaglandins and nitric oxide (NO). In chronic kidney disease (CKD) patients hypertension is extremely common and is aggravated together with the lowering of renal clearance (GFR). The kidneys may be a cause and a culprit of hypertension.

Topics: Atrial Natriuretic Factor; Glomerular Filtration Rate; Humans; Hypertension; Kidney; Kidney Diseases; Renin-Angiotensin System; Water-Electrolyte Balance

Since the discovery of atrial natriuretic peptide (ANP), there has been tremendous progress in our understanding of the physiologic and pathophysiologic, diagnostic, and therapeutic roles of ANP. The diagnostic application of ANP and brain natriuretic peptide (BNP) has been reviewed by many investigators, and meta-analyses of therapeutic use of BNP were reported from the USA. However, there are few reviews concerning the therapeutic use of ANP in patients with various conditions. Therefore, this review focuses on the recent clinical evidence of ANP in therapeutic use and experimental data that rationally support the therapeutic use of ANP.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Glomerular Filtration Rate; Heart Failure; Humans; Kidney Diseases; Mice; Myocardial Infarction; Natriuretic Peptide, Brain; Neovascularization, Physiologic; Receptors, Atrial Natriuretic Factor; Ventricular Remodeling

Randomized controlled trials (RCTs) with atrial natriuretic peptide (ANP) have shown inconsistent effects for renal end-points. The authors aimed to systematically review these trials to ascertain the benefit of ANP in prevention and treatment of acute kidney injury (AKI).. The authors searched MEDLINE, EMBASE, and Cochrane Renal Health Library that investigated ANP in adult patients considered with or at risk for AKI. Outcomes were analyzed separately for prevention and treatment of AKI.. Nineteen RCTs (11 prevention, 8 treatment) involving 1861 participants were included. Pooled analysis of prevention trials showed a trend toward reduction in renal replacement therapy in the ANP group (OR = 0.45, 95% CI, 0.21 to 0.99) and good safety profile, but no improvement in mortality. For the treatment of established AKI, ANP, particularly in high doses, was associated with a trend toward increased mortality and more adverse events. Subgroup analysis of AKI after a major surgery (14 RCTs, 817 participants) showed a significant reduction in renal replacement therapy requirement in the ANP group (OR = 0.49, 95% CI, 0.27 to 0.88). Included RCTs were mostly low- or moderate-quality, underpowered studies.. There are an insufficient number of high-quality studies to make any definite statement about the role of ANP in AKI. Analysis of the existing literature suggests ANP might be associated with beneficial clinical effects when administered in patients undergoing major surgery such as cardiovascular surgery. Its use, in low doses, should be explored further in this setting.

Topics: Acute Disease; Atrial Natriuretic Factor; Evidence-Based Medicine; Humans; Kidney Diseases; Odds Ratio; Perioperative Care; Randomized Controlled Trials as Topic; Renal Replacement Therapy; Risk Assessment; Treatment Outcome

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether atrial natriuretic peptide (ANP) or brain natriuretic peptide (BNP) could be a useful alternative diuretic for patients post cardiac surgery. Altogether more than 250 papers were found using the reported search, of which eight RCTs represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We conclude that the RCTs consistently showed a diuretic effect with increased creatinine clearance, and increased urine volume and reduced usage of conventional diuretics. Lower urea and creatinine levels were also found postoperatively and also reduced decreases in glomerular filtration rate compared to placebo, both in studies of patients with preoperatively normal renal function and those who had impaired function. In addition, two studies found a reduction in the incidence of AF, and renin/aldosterone levels were lower. The NAPA trial of 272 CABG patients with LV dysfunction was the only study to show a shorter ICU stay and reduced early mortality with nesiritide compared to placebo.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Natriuretic Factor; Benchmarking; Cardiac Surgical Procedures; Creatinine; Diuretics; Evidence-Based Medicine; Glomerular Filtration Rate; Humans; Intensive Care Units; Kidney Diseases; Length of Stay; Natriuretic Peptide, Brain; Treatment Outcome; Urea

In recent years, biomarkers have been recognized as important tools for diagnosis, risk stratification, and therapeutic decision-making in cardiovascular diseases. Currently, the clinical potential of several natriuretic peptides is under scientific investigation. The well-known counter-regulatory hormones are atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), dendroaspis natriuretic peptide (DNP) and urodilatin, which play an important role in the homeostasis of body fluid volume. ANP and BNP have already been demonstrated to have diagnostic usefulness in a great number of studies, which have progressed from bench to bedside. This article summarizes existing data on ANP and related peptides in cardiovascular and other disorders, and outlines the potential clinical usefulness of these markers.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Cardiovascular Diseases; Elapid Venoms; Homeostasis; Humans; Intercellular Signaling Peptides and Proteins; Kidney Diseases; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Peptide Fragments; Peptides

Plasma levels of natriuretic peptides are elevated in patients with chronic kidney disease owing to impairment of renal function, hypertension, hypervolemia, and/or concomitant heart disease. Proteinuria and/or immunosuppression also contribute to enhanced plasma levels and increased urinary excretion of natriuretic peptides. Atrial natriuretic peptide (ANP) and particularly brain natriuretic peptide (BNP) levels are linked independently to left ventricular mass and function and predict total and cardiovascular mortality. ANP and BNP decrease significantly during hemodialysis treatment but increase again during the interdialytic interval. Intraperitoneal administration of ANP decreases peritoneal fluid and glucose absorption, as well as lymphatic flow rate. Successful kidney transplant normalizes the plasma levels of natriuretic peptides in the majority of patients. In experimental animals but not in humans, ANP administration protects against ischemic acute renal failure. Since proANP31-67 peptide does not cause hypotension, this vessel dilator may protect the kidney during acute renal failure by intrarenal vasodilation and stimulation of endogenous prostaglandin E2 synthesis.

Topics: Acute Kidney Injury; Animals; Atrial Natriuretic Factor; Cardiovascular Diseases; Humans; Hypertension; Kidney Diseases; Kidney Transplantation; Natriuretic Peptides; Peritoneal Dialysis; Renal Replacement Therapy

Contrast media nephrotoxicity (CMN) in patients with pre-existing renal impairment remains a clinically significant problem. The first step to reduce the chance of CMN is to identify patients at risk through the use of screening questionnaires and renal function measurement. Patients at risk requiring injection of contrast medium (CM) because of important clinical indications should receive a small dose of either non-ionic iso-osmolar dimeric or non-ionic low osmolar monomeric CM and hydration. Intravenous infusion (1 ml/kg body weight/h) of 0.9% saline starting 4 h before CM injection and continuing for at least 12 h afterwards is effective in reducing the incidence of CMN. Prophylactic haemodialysis does not lower the risk of this complication. The value of pharmacological manipulation with renal vasodilators (calcium channel blockers, dopamine, atrial natriuretic peptide, fenoldopam (selective dopamine-1 receptor agonist), prostaglandin E(1), non-selective adenosine receptors antagonist (theophylline), non-selective endothelin receptor antagonist or the antioxidant acetylcysteine has not been fully proven. However, haemofiltration for several hours before and after contrast medium injection offers good protection against CMN in patients with advanced renal disease.

Topics: Acetylcysteine; Alprostadil; Atrial Natriuretic Factor; Contrast Media; Dopamine; Dopamine Agonists; Dose-Response Relationship, Drug; Endothelin Receptor Antagonists; Fenoldopam; Hemofiltration; Humans; Kidney Diseases; Renal Dialysis; Risk Factors; Vasodilator Agents

Nocturia is common in older people and it may be bothersome for both patients and carers. It is most commonly related to bladder storage difficulties and nocturnal polyuria. The former results most frequently from an uninhibited overactive bladder. The latter occurs as a consequence of age-associated changes in the circadian rhythm of urine excretion. The management of an overactive bladder includes both behavioural and drug treatment. The management options for nocturnal polyuria include an afternoon diuretic and desmopressin, but caution is required, particularly with the latter, as it can cause significant hyponatraemia.

Topics: Adult; Aged; Aged, 80 and over; Arginine Vasopressin; Atrial Natriuretic Factor; Circadian Rhythm; Humans; Kidney Diseases; Life Style; Male; Middle Aged; Sleep Wake Disorders; Sodium; Urinary Bladder Diseases; Urination Disorders; Vasopressins; Water-Electrolyte Imbalance

Topics: Atrial Natriuretic Factor; Cardiovascular Diseases; Endothelium; Humans; Kidney Diseases; Lactic Acid; Renin-Angiotensin System; Risk Factors

There is significant evidence to show that many patients with hyponatremia and intracranial disease who were previously diagnosed with SIADH actually have CSW. The critical difference between SIADH and CSW is that CSW involves renal salt loss leading to hyponatremia and volume loss, whereas SIADH is a euvolemic or hypervolemic condition. Attention to volume status in patients with hyponatremia is essential. The primary treatment for CSW is water and salt replacement. The mechanisms underlying CSW are not understood but may involve ANP or other natriuretic factors and direct neural influence on renal function. Future investigation is needed to better define the incidence of CSW in patients with intracranial disease, identify other disorders that can lead to CSW, and elucidate the mechanisms underlying this syndrome.

Topics: Animals; Atrial Natriuretic Factor; Brain Diseases; Diagnosis, Differential; Disease Models, Animal; Fluid Therapy; Humans; Hyponatremia; Inappropriate ADH Syndrome; Kidney Diseases

Vasoactive autocoids with directly opposing actions on the renal vasculature, glomerular function, and in salt and water homeostasis have been demonstrated in the kidney. In the renal cortex, endothelin (ET)-1 and angiotensin-II cause vasoconstriction, decreasing renal blood flow, and glomerular filtration rate, whereas bradykinin and atrial natriuretic peptide cause vasodilation and increase glomerular capillary permeability. ET-1 causes vasoconstriction of the afferent and efferent arteries and outer medullary descending vasa recta, thereby decreasing vasa recta and papillary blood flow, while bradykinin has the opposite effect. ET-1 stimulates cell proliferation, increasing the expression of several genes, including collagenase, prostaglandin endoperoxidase synthase, and platelet-derived growth factor. ET-1 promotes natriuresis via the ET-B receptor, causing down-regulation of the epithelial Na(+) channel in the renal tubule. Thus, ETs affect three major aspects of renal physiology: vascular and mesangial tone, Na(+) and water excretion, and cell proliferation and matrix formation.

Topics: Animals; Atrial Natriuretic Factor; Endothelins; Endothelium, Vascular; Gene Expression Regulation; Humans; Kidney; Kidney Diseases; Microscopy, Confocal; Models, Chemical; Models, Molecular; Receptors, Endothelin; Renin-Angiotensin System; Signal Transduction

A milestone was reached in cardiophysiology when in 1981 DeBold demonstrated that the heart functions as an endocrine gland by injecting an extract of atrial muscle into rats, resulting in an induction of natriuresis and a drop in blood pressure. This observation then led to the discovery of a family of related peptides with slightly different amino acid compositions working in concert to achieve the maintenance of sodium and volume homeostasis. The natriuretic peptide family consists of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), and Urodilatin (URO) with their tissue-specific distribution including the heart (ANP, BNP), brain (ANP, BNP, CNP), endothelial cells (CNP), and kidney (URO). These peptides were thought to be primarily involved in cardiovascular and renal functions but have now proven to play a role in other physiological systems. In view of their known biological effects, therapeutic efficacy from administration of ANP, BNP or URO might be anticipated, for example in acute renal failure or congestive heart failure. A number of clinical trials suggest that application of these peptides may represent a new pharmacological tool in the treatment or prevention of these diseases, but the clinical benefit still needs to be shown in large controlled studies. In addition to therapeutic options it is possible that plasma concentrations of ANP and BNP could play a role as diagnostic and prognostic markers of cardiac dysfunction.

Topics: Amino Acid Sequence; Animals; Atrial Natriuretic Factor; Blood Pressure; Exons; Heart; Humans; Kidney Diseases; Molecular Sequence Data; Natriuresis; Rats; Receptors, Atrial Natriuretic Factor

Cardiac natriuretic peptides (ANP, BNP, and biologically active peptides of the N-terminal proANP1-98) are differently regulated in their production/secretion patterns and clearance rates; consequently, the assay for these peptides may provide complementary (or even different) pathophysiological and/or clinical information. The assay for cardiac natriuretic peptides has been utilized in clinical conditions associated with expanded fluid volume. In particular, this assay can be useful in discriminating between normal subjects and patients in different stages of heart failure and can also be considered a prognostic indicator of long-term survival in patients with heart failure and/or after acute myocardial infarction. Non-competitive immunometric assays (such as two-site IRMAs), even if more expensive, seem to be preferable to RIAs for routinary assay of cardiac peptide hormones because they generally have a better degree of sensitivity, accuracy, and precision.

Topics: Amino Acid Sequence; Atrial Natriuretic Factor; Cardiovascular Diseases; Diabetes Mellitus; Humans; Kidney Diseases; Molecular Sequence Data; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Protein Precursors

Topics: Animals; Atrial Natriuretic Factor; Humans; Kidney Diseases

Topics: Animals; Atrial Natriuretic Factor; Diuretics; Humans; Kidney Diseases; Peptide Fragments; Renal Circulation

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

Progressive systolic dysfunction of the heart results in a broad array of physiologic compensatory mechanisms within the kidney. These mechanisms are primarily stimulated by diminution of the effective arterial blood volume and resultant activation of a biochemical cascade of neurohormonal responses, including activation of the renin-angiotensin-aldosterone system and enhanced release of norepinephrine, arginine vasopressin, prostaglandins, endothelin, and atrial natriuretic peptide. The interaction of these neurohormonal systems within the kidney is complex. Vasoconstriction induced by angiotensin II, arginine vasopressin, and catecholamines may decrease renal perfusion by both endocrine and neural actions. In contrast, systemic pressures may rise, which may facilitate perfusion.

Topics: Adaptation, Physiological; Aldosterone; Angiotensin II; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Volume; Endothelins; Heart Failure; Hemodynamics; Homeostasis; Humans; Kidney Diseases; Norepinephrine; Prostaglandins; Renal Circulation; Renin-Angiotensin System; Systole

The original observation by de Bold et al. (1981) of a rapid, massive, and short-lasting diuretic and natriuretic effect following injection of rat atrial extracts into intact rats, led to the identification, isolation and purification of the atrial natriuretic factor (ANF). ANF is stored in atrial myocytes and released into the blood stream by atrial distension. Available data suggest that the mechanism of ANF-induced natriuresis involves either renal hemodynamic effects, such as the increase in glomerular filtration rate and reduction of medullary tonicity, or direct effect on sodium transport in the medullary collecting ducts. ANF induces relaxation of vascular smooth muscle, decreases blood pressure and cardiac output. All these effects displayed by ANF are associated to the an inhibition of aldosterone, renin and vasopressin release. Most of these actions are mediated by specific high affinity receptors, which are coupled to a particulate guanylate cyclase. Although ANF levels are increased in some disorders, such as severe heart failure, hypertension, chronic renal failure, the role of the peptide is uncertain. To better define the potential physiopathological role and the possible therapeutic implications of this new hormonal system in conditions of disturbed body fluid and sodium homeostasis, further experimental and clinical data must be awaited.

Topics: Atrial Natriuretic Factor; Gene Expression Regulation; Heart Atria; Heart Diseases; Humans; Hypertension; Kidney Diseases; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface

The concept of renal functional reserve (RFR) was introduced in the 80's. The renal functional reserve was defined as the ability of the kidney to increase Renal Plasma Flow (RPF) and Glomerular Filtration Rate (GFR) after a stimulus as a protein load. The absence of RFR defines a state of hyperfiltration which seems to be a detrimental factor for the progression of renal failure. The measure of RFR by a protein load test is thus a mean to detect glomerular hyperfiltration and allows to give adequate diet prescription.

Topics: Atrial Natriuretic Factor; Catecholamines; Glomerular Filtration Rate; Glucagon; Growth Hormone; Humans; Insulin; Kidney; Kidney Diseases; Kidney Function Tests; Kidney Transplantation; Kidney Tubules; Prostaglandins; Renal Circulation; Renin-Angiotensin System

The heart functions as an endocrine organ, releasing atrial natriuretic peptide (ANP), a hormone, in response to sodium and fluid overload. Specifically, ANP is released by cardiac myocytes in response to atrial distension. As a hormone, ANP has far-reaching multiorgan effects. The body systems affected include the cardiovascular, renal, neural, gastrointestinal, and endocrine systems. However, the main effects of this hormone are on the renin-angiotensin-aldosterone system. ANP acts to oppose this system by causing vasorelaxation, blocking the secretion and sodium-retaining effects of aldosterone, and inhibiting renal renin secretion. ANP has many potential implications for clinical practice in both short-term and long-term care of patients with fluid and electrolyte balance. Clinicians may use methods to enhance or block endogenous ANP secretion based on assessment of clinical disorder, cause, status of homeostatic mechanisms, and implications for treatment. In addition, ANP may soon be administered pharmacologically, as well as monitored hematologically, in patients with fluid volume overload. In this article we describe the physiologic effects of ANP and address specific implications for clinical practice.

Topics: Animals; Atrial Natriuretic Factor; Humans; Kidney Diseases; Nursing Diagnosis; Water-Electrolyte Imbalance

The heart atrium, as well as under certain pathophysiological conditions the ventricle, synthesize and release ANP. Exerting natriuretic, diuretic and vasorelaxant effects, this peptide plays an important role in the body's blood volume and blood pressure homeostasis. Whereas the pharmacological actions of ANP have been quite convincingly demonstrated, its physiological and pathophysiological role is less well defined. ANP plasma levels tend to be increased in diseases with salt and water retention, such as essential hypertension, congestive heart failure, renal failure or liver cirrhosis. With regard to its hemodynamic effects, ANP seems to be beneficial in patients with hypertension. ANP appears to have little therapeutic potential as a diuretic in patients with congestive heart failure and liver cirrhosis, possibly due to the decreased renal responsiveness to ANP in these diseases. However, ANP might to be a valuable therapeutic agent in acute renal failure.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Blood Volume; Heart Failure; Homeostasis; Humans; Hypertension; Kidney Diseases; Liver Diseases

Atrial natriuretic factor (ANF) is a cardiac hormone exerting potent cardiovascular and renal effects but its poor intestinal absorption and rapid inactivation have prevented so far its therapeutic utilisation. However inhibition of endogenous ANF metabolism progressively emerges as a novel therapeutic approach in cardiovascular and renal disorders. The critical role played by enkephalinase (membrane metalloendopeptidase, EC 3.4.24.11) in ANF inactivation was deduced from the effects of inhibitors. These compounds not only protect partially exogenous ANF from hydrolysis by some tissue preparations in vitro but also, in vivo, they increase the half-life of the exogenous hormone in plasma and, even more markedly, its recovery in intact form in kidney, a major target organ. In addition, enkephalinase inhibitors increase by two- to three-fold the circulating level of endogenous ANF, even when the latter is already markedly elevated, such as in patients with chronic heart failure. Finally, enkephalinase inhibitors induce a series of ANF-like responses such as natriuresis, diuresis or increase in cGMP excretion which are attributable to the hormone. These pharmacological observations, as well as preliminary clinical trials, suggest that enkephalinase inhibitors may represent a novel class of therapeutic agents with potential applications in congestive heart failure, essential hypertension and various sodium-retaining states.

Topics: Amino Acid Sequence; Animals; Atrial Natriuretic Factor; Cardiovascular Diseases; Humans; Hydrolysis; Kidney Diseases; Molecular Sequence Data; Molecular Structure; Neprilysin

Topics: Atrial Natriuretic Factor; Cardiac Output, Low; Heart Defects, Congenital; Humans; Hypertension; Infant, Newborn; Kidney Diseases; Myocardium; Respiratory Distress Syndrome, Newborn

A new appreciation of the hemodynamic, hormonal, and neural derangements associated with unexplained renal failure in patients with severe liver disease has led to a reappraisal of the limited therapeutic approaches to the hepatorenal syndrome. Although the prognosis generally remains dismal, specific supportive measures are now available for the management of selected patients.

Topics: Atrial Natriuretic Factor; Diagnosis, Differential; Hemodynamics; Hepatorenal Syndrome; Humans; Immersion; Kidney Diseases; Liver Cirrhosis; Prognosis; Renal Circulation; Sympathetic Nervous System; Uremia

ANF is an exciting, newly discovered hormone that has significant potential for furthering our understanding of the complex interactions involved in fluid and electrolyte balance. In addition to effects on water and salt balance, it is a potent vasodilator, as well as inhibitor of renin, angiotensin II, aldosterone, and vasopressin. ANF is primarily produced in the atria, but production in the brain is suggestive of action as a neuropeptide and as a potential regulator of CSF production. Receptors are found throughout the heart, vascular tree, kidney, adrenal gland, and brain. The stimulus for release appears to be atrial stretch, which may be secondary to intravascular fluid changes. It causes hemoconcentration and may be an important regulator of interstitial fluid distribution as well as capillary permeability. Patients with CHF and renal failure have been found to have elevated levels that decrease in response to treatment. Potentially, it may be useful as a therapeutic agent in acute renal failure, CHF and other fluid disturbances. ANF is a testament to the incredible advances in peptide biology. Within 2 years of the discovery, ANF was sequenced and cloned. Since that time, literally thousands of papers describing its actions have been published. Our knowledge about this hormone grows at an exponential rate. It is clear that this hormone is intimately involved in the regulation of fluid and electrolyte balance, vascular tone, and the pathophysiology of CHF but many questions remain unanswered. Continued research will provide many of the missing pieces to this very complex, new hormone system.

Topics: Atrial Natriuretic Factor; Cardiovascular Diseases; Endocrine System Diseases; Humans; Kidney Diseases

Topics: Atrial Natriuretic Factor; Humans; Kidney Diseases

A dualistic function for the natriuretic ATP.inhibiting factor is formulated on the basis of a phenomenon like compensatory renal adaption of residual nephrons: 1. Support of the tubular sodium excretion to the maintenance of homoeostasis of the organism. 2. Inhibition of the forced up vasodilation of the afferent glomerular vessel. It should suggested that the renal vasoconstrictive effect is a part of a protective system for residual nephrons against the pathogenic hyperfiltration and hyperperfusion.

Topics: Animals; Atrial Natriuretic Factor; Blood Proteins; Cardenolides; Digoxin; Glomerular Filtration Rate; Kidney Diseases; Nephrectomy; Nephrons; Saponins; Sodium-Potassium-Exchanging ATPase

Topics: Atrial Natriuretic Factor; Cardiovascular Diseases; Humans; Kidney Diseases; Liver Diseases

Topics: Atrial Natriuretic Factor; Endotoxins; Hepatorenal Syndrome; Humans; Kidney; Kidney Diseases; Prostaglandins; Renin-Angiotensin System; Sympathetic Nervous System

ANF is a newly discovered peptide hormone that has significant implications for critical care physicians. This hormone, released from the heart, is especially responsive to fluid challenges as well as to many of the drugs commonly used in the ICU, including pressor and anesthetic agents. It has potent arterial vasodilating effects in pharmacologic doses and may be an important natural vasodilating agent, especially in the renal vascular bed. In patients on dopamine, it may potentiate the renal vasodilating effect and may provide an effective therapy for developing acute renal failure. Children with congenital heart disease and patients with CHF have elevated levels that clearly alter the aldosterone-angiotensin II system and may help us to understand and treat these conditions more effectively. Additionally, ANF may be a marker for adequacy of treatment in these disease states. The potential uses for ANF include diuresis in patients with fluid overload and diuretic resistance, treatment of CHF, and as a short-acting vasodilator. In the ICU, many therapies affect cardiac pressures and volume regulation. Positive-pressure ventilation may decrease the release of ANF by decreasing venous return and thus contribute to water retention. Drugs used in the ICU may directly affect ANF levels and markedly affect the homeostasis of fluid and electrolyte balance. This hormone system interacts intimately with renin, angiotensin II, and aldosterone. These interactions may play a significant role in the development of essential hypertension. Although not addressed in this article, the treatment and understanding of essential hypertension may be significantly advanced by understanding these relationships. It is clear that ANF acts as a hormone with complex interactions between the heart, volume status, electrolyte balance, renin-angiotensin II-aldosterone, vasopressin, and vascular tone. Although currently no definitive picture exists for these complex interactions, this is an exciting new hormone with significant implications for patient management in the ICU. As research continues, the picture will become clearer and our understanding of this new hormone more precise.

Topics: Animals; Atrial Natriuretic Factor; Endocrine System Diseases; Heart Diseases; Humans; Kidney Diseases

This review examines current understanding about the patient with moderately advanced cirrhosis of the liver and his or her transition to hepatorenal syndrome (HRS). Special emphasis is given to three areas of ongoing research. Atrial natriuretic factor's role in the pathogenesis of salt and water retention is examined, as well as its role in determining volume status in these patients. The current literature regarding prostaglandins (PGs) is reviewed, with emphasis on how vasodilatory PGs appear first to help maintain homeostasis in advanced cirrhosis and how vasoconstrictor thromboxane may then be involved in the transition to HRS. Finally, new findings regarding the liver hormone glomerulopressin are examined, and how deficient release of this may lead to the decrease in glomerular filtration rate seen in HRS.

Topics: Animals; Atrial Natriuretic Factor; Eicosanoic Acids; Glucuronates; Hepatorenal Syndrome; Hormones; Humans; Kidney Diseases; Liver Cirrhosis

Topics: Adrenal Cortex; Animals; Atrial Natriuretic Factor; Biological Transport; Blood Pressure; Heart Atria; Heart Failure; Humans; Hypertension; Immunoenzyme Techniques; Kidney; Kidney Diseases; Molecular Weight; Natriuresis; Radioimmunoassay; Rats; Renin

Renal dysfunction is an important independent prognostic factor in heart failure (HF). Cardiac resynchronization therapy (CRT) improves functional status and left ventricular (LV) function in HF patients with ventricular dyssynchrony, but the impact of CRT on renal function is less defined. We hypothesized that CRT would improve glomerular filtration rate as estimated by the abbreviated Modification of Diet in Renal Disease equation (eGFR).. The Multicenter InSync Randomized Clinical Evaluation (MIRACLE) study evaluated CRT in HF patients with NYHA Class III-IV, ejection fraction or=130 ms. Patients were evaluated before and 6 months after randomization to control (n = 225) or CRT (n = 228). Patients were categorized according to their baseline eGFR: >or=90 (category A), 60

Topics: Atrial Natriuretic Factor; Blood Urea Nitrogen; Cardiac Output, Low; Cardiac Pacing, Artificial; Creatinine; Double-Blind Method; Female; Follow-Up Studies; Glomerular Filtration Rate; Heart Failure; Hematocrit; Hemoglobins; Humans; Kidney; Kidney Diseases; Male; Natriuretic Peptide, Brain; Placebos; Retrospective Studies; Treatment Outcome; Ventricular Function, Left

The purpose of this study was to investigate the efficacy of carperitide (human atrial natriuretic peptide [h-ANP]) in perioperative management in patients with renal dysfunction, especially its kidney-protecting effects.. The subjects were 18 patients who underwent elective cardiac surgery using cardiopulmonary bypass (CPB) with a preoperative serum creatinine (Cr) level of 1.2 mg/dl or more. The subjects were prospectively assigned to 2 groups: an h-ANP-treated group (Group H, n = 10) and a non-h-ANP-treated group (Group N, n = 8). At the beginning of surgery, h-ANP administration was initiated and continued for 5 days or more. The central dose was 0.02 microg/kg/min. The primary end point included the serum Cr level and creatinine clearance (Ccr).. In Group H, Cr level significantly decreased after surgery compared to the preoperative level. The Ccr values were significantly higher 2 and 3 days after surgery than the preoperative values. And the intraoperative urine volume significantly increased. In Group H, an increase in urinary N-acetyl-beta-D-glucosaminidase (NAG) level the day after surgery was significantly inhibited in comparison with Group N.. The results of this study suggest that in patients with renal dysfunction before cardiac surgery, continuous low-dose h-ANP therapy maintains renal function, preventing its deterioration.

Topics: Acetylglucosaminidase; Atrial Natriuretic Factor; Biomarkers; Blood Urea Nitrogen; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Creatinine; Fatty Acid-Binding Proteins; Heart Diseases; Humans; Infusions, Parenteral; Interleukin-6; Kidney Diseases; Perioperative Care; Prospective Studies; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha; Urodynamics

Renal dysfunction in patients with biliary obstruction is associated with extracellular water depletion. This study examined the effect of preoperative saline infusion before biliary drainage on hormonal and renal functional derangements in patients with obstructive jaundice.. In a randomized study, 49 patients with malignant obstructive jaundice were investigated at baseline, on the day of drainage, and at 24 h, 72 h and 7 days after internal endoscopic biliary drainage. Patients were randomized to receive (n = 22) or not to receive (n = 27) 3000 ml normal saline intravenously for 24 h before drainage. Variables analysed included extracellular water volume, creatinine clearance, and serum levels of aldosterone, renin, atrial natriuretic peptide (ANP), vasopressin and albumin.. Preoperative saline infusion produced a rise in creatinine clearance, diuresis, ANP concentration and extracellular water volume but this did not translate into better recovery of renal function after operation. Drainage produced a fall in creatinine clearance in all patients, but hormonal and renal function had recovered by 2 days after restoration of bile flow, independently of preoperative hydration.. Fluid administration expands the extracellular water compartment before drainage but fails to improve renal function after drainage. Definitive improvement in endocrine and renal function requires the restoration of bile flow into the duodenum.

Topics: Adult; Aged; Atrial Natriuretic Factor; Biliary Tract Neoplasms; Bilirubin; Creatinine; Drainage; Endoscopy, Gastrointestinal; Female; Humans; Infusions, Intravenous; Jaundice, Obstructive; Kidney Diseases; Male; Middle Aged; Prospective Studies; Renin; Sodium Chloride

Efficacy and safety assessments for carperitide (alpha-human atrial natriuretic peptide) in previous clinical trials have not mentioned its limitations in practice as therapy for acute heart failure.. A 6-year prospective open-label registry analysis was conducted in the 'real world' of therapy for 3,777 patients with acute heart failure (male 57%, median age 73) treated with 0.085 microg . kg(-1) . min(-1) (median, interquartile 0.05-0.1) of carperitide for 65 h (median, interquartile 22-142); 51% were assessed as class III or IV according to the Killip classification; 82% of the patients were assessed as clinically improved after carperitide treatment. The efficacy limitation was related to the underlying disease (acute myocardial infarction), severity of Killip classification (Class IV), and renal function disturbance. The efficacy was significantly higher in patients with decompensated chronic heart failure (ie, cardiomyopathy, valvular diseases, and hypertensive heart disease). Incidence of adverse events was 16.9%, the most frequent being blood pressure lowering (9.5%), which occurred in the first 3 h of infusion, with 96% of patients recovering or improving without specific treatment. Logistic regression analysis revealed that factors predicting mortality (11.4%) during 7 days of follow-up were age, Killip classification, renal function disturbance, low blood pressure and use of vasopressors.. The clinical condition improved in 82% of patients treated with carperitide. Based on these findings, minute strategy will be established for carperitide therapy within the strata of patient characteristics that may predict the prognosis.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Female; Heart Failure; Humans; Hypotension; Kidney Diseases; Male; Middle Aged; Myocardial Infarction; Prognosis; Regression Analysis; Risk Factors; Severity of Illness Index; Treatment Outcome; Vasoconstrictor Agents

Delayed hypertension (HT) and renal dysfunction (RD) are observed after aortic operations accompanied by infra-renal aortic cross-clamping (AXC). Atrial natriuretic peptide (ANP) has effects on vasodilation and renal protection, and we examined the hypothesis that synthetic human alpha-ANP (hANP) improves the postoperative management for abdominal aortic aneurysm (AAA).. Fifty patients undergoing elective aneurysmectomy for infrarenal-AAA between 1998 and 2001 (M:F = 43:7, mean age 70.5 +/- 7.7 years) were randomly allocated to one of 2 groups; Group H (n = 24) received hANP immediately after operation (initial dose: 0.025 microg/kg/min), and Group C (n = 26) served as a control group.. All patients in Group C required nicardipine hydrochloride (4.41 +/- 1.68 mg/h) for prevention of postoperative HT, whereas only 6 patients in Group H required the increase in hANP dose due to HT (P < 0.0001). Maximum hANP dose was 0.035 +/- 0.019 microg/kg/min. Group H showed significantly smaller furosemide dosage in the initial 3 days (H vs. C; 9.2 +/- 11.0 vs. 58.8 +/- 41.5 mg, P < 0.0001), significantly lower peak-Crn (H vs. C; 1.16 +/- 0.53 vs. 2.58 +/- 1.42 mg/dL, P < 0.0001), and significantly lower plasma renin-activity (7.09 +/- 2.38 vs. 11.52 +/- 4.89 ng/mL/h, P = 0.0002) and aldosterone (51.6 +/- 12.7 vs. 81.2 +/- 34.2 pg/mL, P = 0.0002) on the first postoperative day than Group C did.. These results imply that renin-angiotensin system may play a role in the incidence of postoperative HT and RD, and suggest that hANP infusion is a simple, reliable, and effective method for management during the immediate period after AAA operations.

Topics: Aged; Aldosterone; Aortic Aneurysm, Abdominal; Atrial Natriuretic Factor; Chi-Square Distribution; Female; Humans; Hypertension; Kidney Diseases; Male; Middle Aged; Postoperative Complications; Renin

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

Topics: Atrial Natriuretic Factor; Cardiovascular Diseases; Diabetes Mellitus; Female; Heart Failure; Humans; Kidney Diseases; Male; Natriuretic Peptide, Brain; Natriuretic Peptides

Topics: Albuminuria; Animals; Atrial Natriuretic Factor; Atrial Remodeling; Blood Pressure; Cardiomegaly; Cardiotonic Agents; Dinoprostone; Drug Evaluation, Preclinical; Fibrosis; Glomerular Filtration Rate; Heart; Hypertension; Kidney; Kidney Diseases; Male; Myocytes, Cardiac; Natriuresis; Peptide Fragments; Potassium; Rats; Rats, Inbred Dahl; Smad2 Protein; Sodium Chloride, Dietary; Ventricular Remodeling

Diuretic response is a strong predictor of outcome for admitted patients of acute decompensated heart failure (ADHF). However, little is known about the effects of early diuretic response to carperitide.. We retrospectively analyzed records of 85 patients hospitalized for ADHF who received carperitide as initial treatment and <40 mg furosemide during the early period. The eligible patients were divided into good diuretic responder (GR) group and poor diuretic responder (PR) group on the basis of median urinary volume.. The PR group demonstrated older age, lower body mass index (BMI), lower estimated glomerular filtration rate, and higher blood urea nitrogen (BUN) level, left ventricular ejection fraction, and β-blockers prescribed at baseline than the GR group. The incidence of worsening renal function (WRF) was significantly higher in the PR group than in the GR group. There was no correlation between early intravenous furosemide dose and urinary volume (Spearman correlation, ρ = 0.111, p = 0.312). Multivariate analysis showed that the statistically significant independent factors associated with poor diuretic response to carperitide were BMI (Odds ratio (OR) = 0.82, 95% confidence interval (CI) 0.68-0.94, p = 0.004) and BUN (OR = 1.07, 95%CI 1.01-1.15, p = 0.018). Kaplan-Meier analysis indicated a lower event-free rate in the PR group than in the GR group (log-rank, p = 0.007).. BMI and BUN levels on admission were significant determinants of early poor diuretic response to carperitide. Early poor diuretic response to carperitide was associated with future poor outcomes.

Topics: Aged; Atrial Natriuretic Factor; Blood Urea Nitrogen; Body Mass Index; Diuretics; Female; Furosemide; Glomerular Filtration Rate; Heart Failure; Humans; Kaplan-Meier Estimate; Kidney; Kidney Diseases; Male; Middle Aged; Mortality; Prognosis; Progression-Free Survival

Predictors of worsening renal function (WRF: increase in serum creatinine ≥ 0.3 mg/dl from the value on admission) in patients with acute decompensated heart failure (ADHF) treated by low-dose carperitide (0.01-0.05 μg/kg/min) are unclear.. We retrospectively investigated predictors of WRF within the first 24 h of low-dose carperitide therapy in 205 patients (mean age, 75.6 ± 12.1 years) hospitalized for ADHF and treated with low-dose carperitide between January 2006 and April 2014. WRF occurred in 14 patients (7%). A multivariate adjustment analysis showed that independent predictors of WRF within 24 h were hypotension (systolic blood pressure <90 mmHg) within 12 h (odds ratio, 8.7; 95% confidence interval, 2.38-35.88; P=0.0012) and serum creatinine on admission (odds ratio, 3.64; 95% confidence interval, 1.84-7.67; P=0.0003). In patients with estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2), the rate of WRF occurrence was higher in those complicated by hypotension than in those without hypotension (22.6% [7/31 patients] vs. 4.4% [5/113 patients], P=0.0041). In contrast, in patients with eGFR ≥ 60 ml/min/1.73 m(2), hypotension did not influence the occurrence of WRF (0% [0/9 patients] vs. 3.9% [2/51 patients], P=NS).. Hypotension within 12 h and renal dysfunction on admission are independent predictors of WRF within 24 h in patients with ADHF treated by low-dose carperitide. Hypotension may not cause WRF in patients with eGFR ≥ 60 ml/min/1.73 m(2).

Topics: Acute Disease; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Creatinine; Female; Glomerular Filtration Rate; Heart Failure; Humans; Hypotension; Kidney Diseases; Male; Middle Aged; Retrospective Studies

To assess whether the prognostic significance of cardiovascular (CV) biomarkers, is affected by renal dysfunction (RD) in systolic heart failure (HF).. It is unknown, whether the prognostic significance of CV biomarkers, such as N-terminal-pro-brain-natriuretic-peptide (NT-proBNP), high-sensitive troponin T (hsTNT), pro-atrial natriuretic peptide (proANP), copeptin and pro-adrenomedullin (proADM), is affected by renal function in HF.. Clinical data and laboratory tests from 424 patients with systolic HF were collected prospectively. The patients were followed for 4.5 years (interquartile range: 2-7.7 years). CV biomarkers were analyzed on frozen plasma, and renal function was estimated by the Modification of Diet in Renal Disease (MDRD) formula. Cox proportional hazard models for mortality risk were constructed and tests for interaction between each CV biomarker and RD were performed.. Median age was 73 years (51-83), 29% were female, LVEF was 30% (13-45), 74% were NYHA classes I-II and estimated glomerular filtration rate (eGFR) was 68 ml/min/1.73 m(2) (18-157). A total of 252 patients died. All five biomarkers--log(NT-proBNP) (HR: 2.13, 95% CI: 1.57-2.87:, P<0.001), hsTNT (HR: 3.07, 95% CI: 1.90-4.96 P<0.001), proANP (HR: 1.02, 95% CI: 1.01-1.03, P<0.001), copeptin (HR: 1.02, 95% CI: 1.01-1.03, P=0.008) and proADM (HR: 2.37, 95% CI: 1.66-3.38, P<0.001)--were associated with mortality risk, but not affected by RD (P>0.05 for all interactions).. Established and new CV biomarkers are closely associated with renal function in HF. However, their prognostic significance is not affected by RD, and all CV biomarkers can be used for risk stratification independently of renal function.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Cardiovascular Diseases; Female; Follow-Up Studies; Heart Failure, Systolic; Humans; Kaplan-Meier Estimate; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Neostigmine; Peptide Fragments; Prognosis; Proportional Hazards Models; Risk Factors; Troponin T

Bioimpedance spectroscopy (BIS) is widely used to assess fluid status in hemodialysis (HD) patients. Our purpose is to evaluate filtration coefficients (Lpst) as an alternative test to assess fluid status by utilizing BIS as a reference test.
. 106 HD patients (determined group) were divided into two groups with (EX group: 53) or without excess fluid mass (ExF). ExF calculated from extracellular water and intracellular water measured by BIS. Multiple linear regression equation of Lpst was made using ExF (ExF/DW) and ultrafiltration rate (UFR/DW) to adjust Lpst (AdjLpst). The cut-off values of the tests for detection of EX were determined by receiver-operator characteristic curve analysis. Lpst, AdjLpst, serum atrial natriuretic peptide concentration (ANP), ultrasonically measured inferior vena cava diameter (IVCe/BSA), and blood volume change (Δ BV/TUF/DW) were examined. The detection abilities of these tests were evaluated in the distinct 61 patients (evaluated group).
. Patients of the EX group numbered 29 in the evaluated group. The correlation between AdjLpst and ExF/DW was the highest. The sensitivity of AdjLpst and specificity of Lpst were the highest. The specificity of AdjLpst was equivalent to that of Lpst. Unadjusted and adjusted odds ratios of AdjLpst were the higher (20.80, 95% CI, 5.61-77.10, 16.06, 95% CI 4.00-64.59, respectively) than those of the other tests.
. AdjLpst can detect patients of the EX group more accurately than other tests. Because AdjLpst is related to plasma refilling, it may indicate removable fluid overload. AdjLpst in conjunction with BIS may contribute to more adequate fluid management.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Blood Volume; Capillary Permeability; Electric Impedance; Fluid Therapy; Humans; Kidney Diseases; Linear Models; Logistic Models; Microvessels; Middle Aged; Multivariate Analysis; Odds Ratio; Predictive Value of Tests; Renal Dialysis; ROC Curve; Spectrum Analysis; Ultrasonography; Vena Cava, Inferior; Water-Electrolyte Balance; Water-Electrolyte Imbalance

The aim of this study was to evaluate the efficacy of carperitide in maintaining renal function during intraoperative and postoperative management of patients with renal dysfunction undergoing elective cardiovascular surgery.. The subjects were 88 patients with a preoperative serum creatinine level ≥1.2 mg/dl who underwent elective cardiovascular surgery using cardiopulmonary bypass. They were prospectively divided into a group that received carperitide from the start of surgery (carperitide group, n = 44) and a group that was not given carperitide (control group, n = 44). Carperitide infusion was initiated at the beginning of surgery and was continued for ≥5 days, with the central dose being 0.02 g/kg/min. The primary endpoint was the serum creatinine level on postoperative day (POD) 3.. The serum creatinine levels on PODs 3, 4, and 7 were significantly lower, and creatinine clearance on PODs 2 and 3 was significantly higher in the carperitide group than in the controls. One patient in the control group and no patient in the carperitide group required continuous hemodiafiltration, but the difference was not statistically significant.. Continuous low-dose infusion of carperitide from the start of cardiovascular surgery maintained renal function in patients with preoperative renal dysfunction.

Topics: Acute Kidney Injury; Aged; Atrial Natriuretic Factor; Biomarkers; Cardiac Surgical Procedures; Creatinine; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Japan; Kidney; Kidney Diseases; Male; Middle Aged; Prospective Studies; Time Factors; Treatment Outcome; Vascular Surgical Procedures

In pregnancy, trophoblast invasion and uterine spiral artery remodelling are important for lowering maternal vascular resistance and increasing uteroplacental blood flow. Impaired spiral artery remodelling has been implicated in pre-eclampsia, a major complication of pregnancy, for a long time but the underlying mechanisms remain unclear. Corin (also known as atrial natriuretic peptide-converting enzyme) is a cardiac protease that activates atrial natriuretic peptide (ANP), a cardiac hormone that is important in regulating blood pressure. Unexpectedly, corin expression was detected in the pregnant uterus. Here we identify a new function of corin and ANP in promoting trophoblast invasion and spiral artery remodelling. We show that pregnant corin- or ANP-deficient mice developed high blood pressure and proteinuria, characteristics of pre-eclampsia. In these mice, trophoblast invasion and uterine spiral artery remodelling were markedly impaired. Consistent with this, the ANP potently stimulated human trophoblasts in invading Matrigels. In patients with pre-eclampsia, uterine Corin messenger RNA and protein levels were significantly lower than that in normal pregnancies. Moreover, we have identified Corin gene mutations in pre-eclamptic patients, which decreased corin activity in processing pro-ANP. These results indicate that corin and ANP are essential for physiological changes at the maternal-fetal interface, suggesting that defects in corin and ANP function may contribute to pre-eclampsia.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Case-Control Studies; Cells, Cultured; Disease Models, Animal; Female; Gene Expression Regulation; HEK293 Cells; Humans; Ischemia; Kidney; Kidney Diseases; Mice; Mice, Knockout; Mice, Transgenic; Mutation; Pre-Eclampsia; Pregnancy; Serine Endopeptidases; Trophoblasts; Uterine Artery; Uterus

Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease. We investigated the effectiveness of human atrial natriuretic peptide (hANP) infusion in CKD patients undergoing coronary artery bypass grafting (CABG).. We analyzed 134 consecutive cases in which CABG had been performed in our hospital from 2002 to 2005. They were divided into four groups: Group A (n = 19) was CKD + placebo, Group B (n = 30) was non-CKD + placebo, Group C (n = 22) was CKD + hANP, and Group D (n = 63) was non-CKD + hANP). The serum creatinine (mg/dl) and estimated glomerular filtration rate (ml/min/1.73 m²) were measured as evaluation values.. The value of sCr changed preoperatively and at 1 year postoperatively from 1.09 ± 0.09, 51.3 ± 4.4 to 1.26 ± 0.42, 49.4 ± 14.4 in Group A, from 0.77 ± 0.14, 75.5 ± 12.1 to 0.91 ± 0.40, 72.3 ± 19.5 in Group B, from 0.99 ± 0.12, 54.8 ± 3.0 to 0.93 ± 0.16, 64.2 ± 12.3 in Group C and from 0.77 ± 0.13, 77.7 ± 13.4 to 0.83 ± 0.17, 75.9 ± 16.2 in Group D, respectively. There was a significant difference between Group A and Group C regarding the change of creatinine (p =0.0022).. Our study has confirmed that an infusion of hANP during CABG in patients with CKD not only improves perioperative renal function, but also prevents the progression of CKD.

Topics: Aged; Analysis of Variance; Atrial Natriuretic Factor; Biomarkers; Chi-Square Distribution; Chronic Disease; Coronary Artery Bypass; Coronary Artery Disease; Creatinine; Female; Glomerular Filtration Rate; Humans; Infusions, Parenteral; Japan; Kidney; Kidney Diseases; Male; Middle Aged; Randomized Controlled Trials as Topic; Retrospective Studies; Time Factors; Treatment Outcome

We investigated the role of heme oxygenase (HO), adiponectin, and atrial natriuretic peptide (ANP) in uninephrectomized (UnX) deoxycorticosterone-acetate (DOCA)-salt hypertensive rats, a volume-overload model characterized by elevated endothelin-1 (ET-1), mineralocorticoid-induced oxidative/inflammatory insults, fibrosis, hypertrophy, and severe renal histopathological lesions that closely mimic end-stage renal disease (ESRD). HO was enhanced with heme arginate (HA) or blocked with chromium mesoporphyrin (CrMP). Histological, morphological/morphometrical, quantitative reverse transcription-polymerase chain reaction, Western blot, enzyme immunoassay, and spectrophotometric analysis were used. Our experimental design included the following groups of rats: A, controls [surgery-free Sprague-Dawley, UnX-sham, UnX-salt (0.9% NaCl + 0.2% KCl), and UnX-DOCA]; B, UnX-DOCA-salt hypertensive; C, UnX-DOCA-salt + HA; D, UnX-DOCA-salt + HA + CrMP; E, UnX-DOCA-salt + CrMP; F, UnX-DOCA-salt + captopril; G, UnX-DOCA-salt + L-arginine; H, UnX-DOCA-salt + spironolactone; and I, UnX-DOCA-salt + vehicle. HA lowered blood pressure and abated kidney hypertrophy and renal lesions, including glomerulosclerosis, tubular dilation, tubular cast formation, interstitial mononuclear cell infiltration, glomerular hypertrophy, and renal-arteriolar thickening in UnX-DOCA hypertension. Correspondingly, HO activity, adiponectin, adenosine monophosphate-activated protein kinase (AMPK), ANP, cGMP, antioxidants such as bilirubin, ferritin, superoxide dismutase, and catalase, and total antioxidant capacity were increased, whereas ET-1, transforming growth factor beta (TGF-beta), fibronectin, and 8-isoprostane were abated. These were accompanied by reduced proteinuria/albuminuria, but increased creatinine clearance. Interestingly, HA was more renoprotective than sipronolactone, L-arginine, and captopril, whereas the HO blocker CrMP exacerbated oxidative injury, aggravating renal lesions and function. Because 8-isoprostane stimulates ET-1 to potentiate oxidative stress and fibrosis, up-regulating HO-1 enhanced tissue antioxidant status alongside cellular targets such as adiponectin, AMPK, ANP, and cGMP to suppress ET-1, TGF-beta, and fibronectin with a corresponding decline of renal lesions, proteinuria/albuminuria, and thus improved renal function. The potent renoprotection of HA could be explored to combat renal hypertrophy and histopathological lesions characteristic of ESRD.

Topics: Adiponectin; Animals; Arginine; Atrial Natriuretic Factor; Blood Pressure; Blotting, Western; Desoxycorticosterone; Disease Models, Animal; Endothelin-1; Heme; Heme Oxygenase (Decyclizing); Hypertension; Kidney; Kidney Diseases; Male; Mineralocorticoids; Rats; Rats, Sprague-Dawley

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

Natriuretic peptides control cardiovascular functions through diuretic, natriuretic, and vasodilatory properties. Several anthropometric, cardiac and renal variables were found to be independently correlated to their levels. Few studies, however, systematically investigated the independent determinants of natriuretic peptide levels in large populations.. The present analysis was carried out in a large unselected sample of adult male population in Southern Italy (The Olivetti Heart Study, n = 806 men, mean age = 59.5, range 35-82 years). We examined the relationship of plasma natriuretic peptide-proatrial natriuretic peptide (NT-proANP) levels with relevant anthropometric, clinical and biochemical variables; the impact of age; and the association of NT-proANP levels with cardiovascular risk.. NT-proANP was directly associated to age, pulse pressure (PP), renal sodium fractional excretion (FENa) (P < 0.005), and inversely to diastolic blood pressure (DBP), heart rate (HR), creatinine clearance, body mass index (BMI), arm and leg circumferences (P < 0.005). After adjustment for age, DBP, creatinine clearance, FENa and HR remained independent determinants of NT-proANP levels (all P < 0.01, cumulative R = 0.186). Upon stratification of our population by tertile of age, NT-proANP was significantly associated (P

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Algorithms; Atrial Natriuretic Factor; Blood Pressure; Body Weights and Measures; Cardiovascular Diseases; Creatinine; Heart Rate; Humans; Italy; Kidney Diseases; Male; Middle Aged; Protein Precursors; Risk Assessment; Risk Factors; Sodium

Recovery from ischemic acute kidney injury requires the replacement of damaged tubular cells. This repair process involves epidermal growth factor (EGF) synthesized in medullary the thick ascending limbs (mTAL) of Henle. Atrial natriuretic peptide (ANP), a hormone synthesized by the cardiac atria, increases glomerular filtration rate and renal medullary blood flow. However, the effects of ANP on renal recovery after I/R-induced renal injury remain unclear. We therefore examined whether human ANP enhances recovery from I/R-induced renal injury by reducing damage to EGF-producing kidney cells in a rat model. Male Wistar rats weighing 200-240 g were observed for 48 h after reperfusion following 45-min renal ischemia. Rats were intravenously administered alpha-human ANP (alpha-hANP) at 0.2 microg/kg/min beginning immediately after ischemia and continuing for 2 h after reperfusion. Outer medullary blood flow (OMBF), EGF mRNA, serum blood urea nitrogen (BUN) and creatinine levels as indicators of glomerular function were measured, while urinary N-acetyl beta-D-glucosaminidase (NAG) was used as a specific indicator of proximal tubular function. OMBF was increased by alpha-hANP after reperfusion and maintained significantly higher mRNA level of EGF in the kidney 24 h after reperfusion. I/R-induced increases in serum concentrations of BUN and creatinine and urinary concentrations of NAG were also reduced by alpha-hANP, with improved histopathological changes, including acute tubular necrosis at 24-48 h after reperfusion. This report is the first to demonstrate that alpha-hANP accelerates recovery following renal ischemic insult by reducing the damage to EGF-producing kidney cells.

Topics: Acute Kidney Injury; Animals; Atrial Natriuretic Factor; Blood Urea Nitrogen; Creatinine; Epidermal Growth Factor; Humans; Kidney; Kidney Diseases; Male; Rats; Rats, Wistar; Renal Circulation; Reperfusion Injury; Urea

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

To determine if natriuretic peptide concentrations are increased in cats with systemic hypertension and/or chronic kidney disease (CKD).. 22 normal cats, 13 normotensive cats with mild-moderate CKD (NT-CKD), 15 hypertensive cats with mild-moderate CKD (HT-CKD) and 8 normotensive cats with severe CKD (NT-CKD-severe).. N-terminal pro-B-type (NT-proBNP) and pro-A-type (NT-proANP) natriuretic peptides were measured in plasma samples from all cats using commercially available assays and concentrations in the normal and diseased groups compared using non-parametric statistical tests. Spearman's rank correlation was used to test for an association between natriuretic peptide and creatinine concentrations.. NT-proANP was significantly higher in the NT-CKD-severe than the normal group of cats (P=0.006) but there were no other differences between groups. NT-proBNP concentrations were significantly higher in the HT-CKD group than both the normal (P<0.001) and the NT-CKD (P<0.001) groups. NT-proBNP concentrations were also higher in the NT-CKD-severe (P<0.001) and the NT-CKD (P=0.005) groups than the normal group. NT-proANP but not NT-proBNP was significantly and positively associated with plasma creatinine concentration.. Measurement of NT-proBNP shows promise as a diagnostic marker for systemic hypertension in the cat. Its concentration is not significantly increased in cats with mild-moderate normotensive CKD.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Case-Control Studies; Cat Diseases; Cats; Creatinine; Female; Hypertension; Kidney Diseases; Male; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors; ROC Curve; Sensitivity and Specificity; Severity of Illness Index; Statistics, Nonparametric

Topics: Atrial Natriuretic Factor; Biomarkers; Cardiac Surgical Procedures; Creatinine; Heart Diseases; Humans; Kidney; Kidney Diseases; Reproducibility of Results; Research Design; Treatment Outcome

A 64-year-old man presented with chief complaints of exertional dyspnea and palpitation. He had previously undergone left nephrolithotomies twice. A chest roentgenogram showed pleural effusion on both sides with cardiac dilation, and electrocardiography showed a frequent occurrence of ventricular premature contractions. An echocardiogram showed diffuse hypokinesis of the left ventricular wall motion (ejection fraction, 45%) and dilation of the left ventricle (left ventricular end-diastolic dimension, 61 mm). We administered diuretics, ACE inhibitors and a beta-adrenergic blocking agent after making a diagnosis of cardiac insufficiency. Because coronary angiography showed 90% stenosis of the left anterior descending coronary artery (No. 7), we performed coronary angioplasty in this locus. Though both the left ventricular wall motion and ejection fraction improved, and the clinical symptoms disappeared, the left ventricular end-diastolic dimension, and arrhythmia did not improve. Furthermore, the brain natriuretic peptide increased despite these treatments. Thereafter, a left renal artery aneurysm (extrarenal aneurysm measuring 5 cm in diameter and an intrarenal aneurysm measuring 3 cm in diameter) and a left renal arteriovenous fistula were discovered when abdominal echography was performed because of epigastric discomfort. As a result, a left total nephrectomy was performed. Subsequently, the left ventricular end-diastolic dimension and arrhythmia improved, and the brain natriuretic peptide returned to a normal value. We herein report a case that developed cardiac insufficiency due to a renal aneurysm and renal arteriovenous fistula after undergoing left nephrolithotomies twice.

Topics: Aged; Aneurysm; Arteriovenous Fistula; Atrial Natriuretic Factor; Cardiac Output, Low; Humans; Kidney; Kidney Diseases; Male; Natriuretic Peptide, Brain; Renal Artery

Left ventricular hypertrophy (LVH), which is a strong predictor of mortality in patients with endstage renal disease, is present in over 70% of patients commencing dialysis. However, only a few studies on LVH are available in patients before the start of dialysis treatment. The purpose of this study was to evaluate the prevalence and clinical correlates of LVH in patients with advanced stages of chronic kidney disease(CKD). We performed a cross sectional study of 90 patients who had renal diseases but no history of either cardiovascular diseases or arrhythmia. Circulating levels of human atrial natriuretic peptide (hANP) were also measured. LVH was present in 40.0% of the study population. The prevalence of LVH tended to increase with progression of renal decline: 22.7% in stage 3, 43.6% in stage 4, and 48.3% in stage 5 (creatinine clearance >10 mL/min) (p = 0.15). Univariate analyses revealed that hANP and albumin were significantly different between the groups with and without LVH. Stepwise logistic regression analysis showed that hANP and albumin were selected as the independent risk factors. These findings suggest that strict control of body fluid and nutrition could prevent the progression of LVH, and as a result, could attenuate the risk of cardiovascular events in CKD.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Cross-Sectional Studies; Dialysis; Female; Humans; Hypertrophy, Left Ventricular; Kidney Diseases; Male; Middle Aged; Regression Analysis; Risk Factors; Serum Albumin

Measurement of natriuretic peptides, particularly brain natriuretic peptide (BNP) is an established method for the diagnosis of cardiovascular disorders, chiefly left ventricular (LV) dysfunction. The influence of renal function on the diagnostic utility of natriuretic peptides is unclear.. We performed a cross-sectional study of 296 patients with renal disease but no history of cardiac disease using echocardiography to assess LV mass and function. Circulating levels of atrial natriuretic peptide (ANP) and BNP were also measured.. The incidence of LV hypertrophy increased with progressive renal dysfunction; from 39% in patients with near-normal renal function, to 80% in renal transplant patients. There was a negative correlation between both ANP and BNP, and glomerular filtration rate (GFR) (ANP: r = -0.28, P<0.001; BNP: r = -0.40, P<0.001). Serum ANP and BNP had sensitivity and specificity for LV hypertrophy of 39.9%, 87.4% (ANP) and 61.4%, 67.6% (BNP) respectively. Sensitivity and specificity for LV dysfunction was 77.2%, 32.4% (ANP) and 71.8%, 40.0% (BNP). Significant confounders in determining serum ANP were haemoglobin, beta blockade and albumin, while serum BNP levels were significantly confounded by GFR, albumin, haemoglobin, beta blockade and age.. Across a spectrum of renal dysfunction, GFR is a more important determinant of serum BNP than ventricular function, and several factors are predictors of natriuretic peptide levels. In chronic kidney disease, the use of natriuretic peptides to diagnose LV hypertrophy must be interpreted in light of these other factors. The use of these peptides in renal dysfunction to diagnose LV dysfunction may be of limited value.

Topics: Adult; Atrial Natriuretic Factor; Cardiomyopathies; Chronic Disease; Cross-Sectional Studies; Female; Humans; Hypertrophy, Left Ventricular; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain

The aim was to evaluate the factors determining preoperative renal dysfunction in patients with obstructive jaundice.. In a prospective cross-sectional observational study, 63 patients, 27 with benign and 36 with malignant obstructive jaundice, were investigated at admission and compared with 25 healthy control subjects. Variables analysed included extracellular body water (ECW) compartment, plasma levels of aldosterone, renin, atrial natriuretic peptide, vasopressin, nitric oxide, endothelin (ET) 1 and prostaglandin E2 (PGE2), urinary nitric oxide and PGE2, serum albumin and renal function.. The metabolic profile of obstructive jaundice was characterized by a depletion of the ECW (P = 0.004), and increased plasma levels of atrial natriuretic peptide (P < 0.001), ET-1 (P = 0.044), vasopressin (P = 0.017), aldosterone (P = 0.005) and renin (P = 0.001). Increased plasma (P < 0.001) and urinary (P = 0.001) PGE2 levels were also found. Fifty-four per cent of patients had a creatinine clearance of less than 70 ml/min. In multivariate analysis, serum bilirubin, renin, ET-1, PGE2, decreased urinary sodium excretion and age were identified as predictors of renal dysfunction.. Renal dysfunction in patients with obstructive jaundice was associated with the degree of biliary obstruction, age of the patient and reduced urinary sodium excretion. These alterations were closely related to derangements in sodium- and water-regulating hormones.

Topics: Atrial Natriuretic Factor; Dinoprostone; Endothelin-1; Female; Humans; Jaundice, Obstructive; Kidney Diseases; Male; Middle Aged; Multivariate Analysis; Prospective Studies; Regression Analysis; Risk Factors; Water-Electrolyte Imbalance

Topics: Acute Disease; Atrial Natriuretic Factor; Biomarkers; C-Reactive Protein; Coronary Disease; Creatinine; Glycated Hemoglobin; Humans; Inflammation; Kidney Diseases; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Risk Assessment; Risk Factors; Syndrome

To prolong the half-life and enhance the biological activity of the human atrial natriuretic peptide (hANP), a peptide hormone, which is synthesized and released mainly by cardiac atrial myocytes and possesses potent natriuretic, diretic, and vasorelaxant properties.. The site-directed mutation technique based on polymerase chain reaction was performed to get the mutant of the human ANP gene (mhANP), and the retroviral expression vector, pLHY24, in which mhANP gene is under the transcriptional control of the human cytomegalovirus promoter, was constructed. The naked plasmid DNA of pLHY24 and positive control vector, pLHY19, in which the wild-type hNAP gene is in the same conditions as mhANP gene in pLHY24, and negative control vector, pLNCX without purpose gene, at a dose of 5 mg/kg body weight was injected intramuscularly into the rats with experimental renal disorder induced with adriamycin (ADR), respectively.. DNA sequencing result proved that the respected mhANP gene with the point mutations of TTC(131)/Phe-->TCC/Ser and ATG(135)/Met-->ATA/Ile has been obtained. In comparison with negative control group (87 +/- 7.1 pg/ml), a single intramuscular injection of expression vector harboring mhANP or hANP gene resulted in an obvious increase in plasma level of mhANP (107 +/- 7.8 pg/ml, t = 4.65, P < 0.01) or hANP (113 +/- 8.6 pg/ml, t = 5.71, P < 0.01) 5 days after injection. A significant elevation in the ratio of urine volume to body weight was occurred after both of mhANP gene and hANP gene delivery as compared with negative control and the effect lasted for more than 15 days. The diuretic activity of mhANP gene delivery was 1.6-, 2.0-, and 1.9-fold higher than that of hANP gene 5, 10, and 15 days after gene transfer, respectively. However, there were no statistical differences in the concentrations of K(+) and Na(+) in urine.. Both of mhANP and hANP gene delivery into the rats with experimental nephropathy could improve their directic function obviously and the diuretic activity of the former is stronger than that of the latter significantly.

Topics: Animals; Atrial Natriuretic Factor; Diuresis; Genetic Therapy; Kidney Diseases; Male; Mutagenesis, Site-Directed; Mutation; Proteinuria; Rats; Rats, Wistar

In order to explore the feasibility of gene therapy strategy based on the human atrial natriuretic peptide (hANP) gene delivery for the treatment of nephropathy and compare the diuretic activities of the hANP gene injected intramuscularly(i.m.) and intravenously(i.v.), the naked retroviral vector DNA harboring the hANP cDNA under the control of retroviral 5' long terminal repeat at a dose of 5 mg/kg body weight was injected i.m. or i.v. into the nephrotic model rats induced with adriamycin(ADR) injected i.v. at a dose of 7.5 mg/kg body weight. A single injection of the hANP gene resulted in a marked elevation in plasma level of hANP 5 days after gene delivery and a significant increase in the ratio of urine volume to body weight and the diuretic effect continued for more than 15 days. In addition, there was a significant rise in the body weight of treatment groups as compared with that of negative control group and no difference in the concentrations of electrolytes in urine between groups. There was no significant differences in total effects resulted from the two routes of gene delivery and the way of gene delivery through the skeletal muscle is simpler and easier. These results suggest that somatic gene delivery of the hANP gene could enhance the renal functions in nephrotic rats significantly and would be a potential strategy for the treatment of renal disorders.

Topics: Animals; Atrial Natriuretic Factor; Body Weight; Disease Models, Animal; Diuresis; Doxorubicin; Genetic Therapy; Humans; Injections, Intramuscular; Injections, Intravenous; Kidney Diseases; Proteinuria; Rats; Rats, Wistar

Epidemiological studies have produced evidence that unfavorable intrauterine environments during fetal life may lead to adverse outcomes in adulthood. We have previously shown that a low-sodium diet, given to pregnant rats over the last week of gestation, results in intrauterine growth restriction (IUGR). We hypothesize that pups born with IUGR are more susceptible to the development of hypertension in adulthood. IUGR fetuses and rats aged 1 wk were characterized for organ growth and renal morphogenesis. The adults (12 wk) were evaluated for weight, systolic blood pressure, activity of the renin-angiotensin-aldosterone system (RAAS), and renal function; hearts and kidneys underwent a histological examination. Brain and cardiac ventricle-to-body ratios were increased in IUGR fetuses compared with age-matched controls, whereas the kidney-to-body ratio was unchanged. Systolic blood pressure was elevated in both IUGR male and female adults. Plasma aldosterone levels were not correlated with increased plasma renin activity. Moreover, urinary sodium was decreased, whereas plasma urea was elevated in both males and females, and creatinine levels were augmented only in females, suggesting a glomerular filtration impairment in IUGR. In our model of IUGR induced by a low-sodium diet given to pregnant rats, high blood pressure, alteration of the RAAS, and renal dysfunction are observed in adult life. Differences observed between male and female adults suggest the importance of gender in outcomes in adulthood after IUGR.

Topics: Aging; Angiotensins; Animals; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Corticosterone; Female; Fetal Growth Retardation; Heart Ventricles; Hypertension; Kidney; Kidney Diseases; Kidney Function Tests; Kidney Glomerulus; Male; Organ Size; Pregnancy; Rats; Rats, Sprague-Dawley; Renin; Renin-Angiotensin System; RNA, Messenger

Biologically active N-terminal fragments such as proANP(1-30), proANP(31-67), and proANP(1-98) derive from the prohormone of alpha-human atrial natriuretic peptide [proANP(99-126) or alpha-ANP]. No systematic data are available for patients with different kidney diseases.. Specific immunoassays were developed to determine plasma and urine concentrations of these fragments in 121 patients with different degrees of kidney function and urinary protein excretion, respectively.. In patients with kidney disease and normal renal function without proteinuria, circulating proANP(1-30) and proANP(31-67) increased 2.8-fold and 6.5-fold, respectively. Urinary excretion of proANP(31-67) increased by a factor of 7.7 in these patients, whereas proANP(1-30) was not affected. Patients with impaired renal function had a dramatic increase of urinary proANP(31-67) excretion even before serum creatinine levels started to rise. The progression of renal failure caused a significant rise of circulating proANP(1-30) (4.3-fold) and proANP(31-67) (3.0-fold) compared with patients with normal renal function. Urinary excretion of proANP peptides significantly increased, particularly when the serum creatinine level was> 5.0 mg/dL [proANP(1-30) 26-fold, proANP(31-67) 8.4-fold]. Urinary excretion of proANP(1-30) increased up to 4.4-fold and urinary excretion of proANP(31-67) increased up to 2.4-fold in patients with proteinuria in excess of 3 g/24 h.. Plasma concentrations and urinary excretion of proANP(1-30) and proANP(31-67) are affected by kidney disease and function, but not by proteinuria per se. It is proposed that the diseased kidney increases early urinary excretion of proANP fragments to participate in the regulation of renal function as well as sodium and water excretion.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Case-Control Studies; Creatinine; Female; Humans; Kidney; Kidney Diseases; Male; Middle Aged; Peptide Fragments; Protein Precursors; Proteinuria

Successful kidney transplantation normalizes elevated proatrial natriuretic peptide (proANP) plasma concentrations of renal failure patients in the early posttransplant period. We evaluated plasma and urinary proANP fragments in the late posttransplant period.. Immunoreactive proANP(1-30) and proANP(31-67) were determined in 389 renal transplant (Rtx) recipients in the long-term, follow-up period and in 16 healthy controls.. Rtx recipients had significantly higher concentrations of proANP(1-30) and proANP(31-67) in both plasma and urine than healthy controls. Although their graft function was normal, all of these long-term Rtx recipients were taking glucocorticoids, which increase proANP(1-30) and proANP(31-67) in the circulation to the extent found in this investigation. Two-thirds of these recipients were also taking cyclosporine, which also increases atrial peptides. Urinary proANP(31-67) was significantly higher than urinary proANP(1-30); 5.5-fold in Rtx patients and 2-fold in controls. Deterioration of renal graft function was associated with a rise of plasma proANP(1-30) from 0.98+/-0.66 to 6.28+/-3.55 nmol/l (P<0.0001) and plasma proANP(31-67) from 1.81+/-1.04 to 7.89+/-3.76 nmol/l (P<0.0001). Urinary excretion of proANP(1-30) increased from 0.27+/-0.34 to 5.96+/-5.07 nmol/24 hr (P<0.0001) and proANP(31-67) from 1.45+/-0.85 to 12.23+/-5.12 nmol/24 hr (P<0.0001). Also proteinuria enhanced plasma and urinary proANP fragments.. ProANP(1-30) and proANP(31-67) of Rtx recipients are affected by immunosuppression, hypertension, renal failure, and proteinuria. One would have expected proANP(1-30) and proANP(31-67) not to normalize because of the glucocorticoids that they were receiving.

Topics: Adult; Aged; Atrial Natriuretic Factor; Creatinine; Female; Humans; Kidney; Kidney Diseases; Kidney Transplantation; Male; Middle Aged; Peptide Fragments; Postoperative Period; Protein Precursors; Proteinuria; Reference Values

To evaluate blood pressure in a population-based cohort with urographic renal scarring after childhood urinary tract infection.. Follow-up investigation 16-26 years after the first recognized urinary tract infection.. University out-patient clinic for children with urinary infections serving the local area.. From the original cohort of 1221 consecutive children with first urinary tract infection diagnosed during 1970-1979, 57 of 68 with non-obstructive renal scarring participated as well as 51 matched subjects without scarring.. 24 h ambulatory blood pressure.. Acceptable blood pressure monitorings were obtained from 53 individuals with and 47 without scarring. There were no significant differences between the two groups even when only patients with the most extensive scarring (individual kidney clearance < 30 ml/min per 1.73 m2) or patients with bilateral scarring were compared with the non-scarring group. Mean systolic or diastolic blood pressure above +2 SD were found in 5/53 (9%) and 3/47 (6%) in the scarring and non-scarring group, respectively. Plasma renin activity, angiotensin II and aldosterone concentrations were not significantly different, but atrial natriuretic protein was significantly higher in the scarring group (P = 0.004).. This study demonstrates a low risk of hypertension two decades after childhood urinary tract infection. It should be stressed that the patients with renal scarring were under close supervision throughout childhood. Those with scarring had higher concentrations of atrial natriuretic protein which might indicate a counter-regulation mechanism.

Topics: Adolescent; Adult; Atrial Natriuretic Factor; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cicatrix; Cohort Studies; Female; Follow-Up Studies; Humans; Hypertension; Kidney Diseases; Male; Risk Factors; Time Factors; Urinary Tract Infections

Cyclosporine induces daily renal hypoperfusion in subjects with normal atrial natriuretic peptide (ANP) levels, but its acute effects in heart transplant patients with increased ANP remain to be determined.. Cyclosporinemia and creatinine clearance were monitored during 7 hours following cyclosporine administration in 6 heart transplant patients.. No acute cyclosporine-induced decrease in creatinine clearance was observed after heart transplantation. These data suggest that maintenance cyclosporine dose may be less nephrotoxic than suspected and that increased ANP might protect the renal function late after heart transplantation.

Topics: Acute Disease; Atrial Natriuretic Factor; Biomarkers; Creatinine; Cyclosporine; Glomerular Filtration Rate; Graft Rejection; Heart Failure; Heart Transplantation; Humans; Immunosuppressive Agents; Kidney Diseases; Male; Middle Aged; Prognosis

Plasma levels of natriuretic peptides are used as diagnostic markers of heart failure. The aim of this study was to analyse the relation between plasma levels of N-terminal proatrial natriuretic peptide (Nt-proANP) and renal function, and to develop reference values in children. Nt-proANP was measured in the plasma of 86 patients whose glomerular filtration rate (GFR) was determined by use of the X-ray contrast medium iohexol and a fluorescence technique. Blood samples for Nt-proANP were also collected in 399 reference children, aged 0 - 15 years. The relationship between Nt-proANP and GFR was examined using a multiple regression analysis. The mean value of Nt-proANP was markedly higher in children with heart failure than in children with malignant or urologic diseases (p<0.001). The variability in plasma levels of Nt-proANP was mainly (adjusted R2=0.81) explained by the following four variables: presence of heart failure, GFR, age and previous treatment with anthracyclins. Plasma levels of the peptide are raised at birth, but fall rapidly to adult levels. We conclude that the plasma levels of Nt-proANP are age-dependent. Moderately elevated values were registered in children with severe renal impairment. Heart failure is regularly associated with excessive elevation of Nt-proANP in plasma. Our findings suggest that the influence of heart failure on levels of this peptide in children greatly exceeds the influence of renal dysfunction.

Topics: Adolescent; Age Factors; Atrial Natriuretic Factor; Chemistry, Clinical; Child; Child, Preschool; Creatinine; Female; Glomerular Filtration Rate; Heart Failure; Humans; Infant; Infant, Newborn; Kidney; Kidney Diseases; Male; Protein Precursors; Reference Values; Ventricular Function

Topics: Alprostadil; Atrial Natriuretic Factor; Contrast Media; Endothelin Receptor Antagonists; Humans; Kidney Diseases

A state of normokalemic renal sodium wasting associated with an apparently inappropriate secretion of atrial natriuretic peptide (ANP) has not been previously recognized. We here report an 11-year-old boy who presented with a chronic "salt-losing" nephropathy manifested by normonatremic or mildly hyponatremic extracellular fluid volume depletion, hypodipsia, absence of salt appetite, normokalemic metabolic alkalosis, hyper-reninemic hyperaldosteronism, hypertrophy of the juxtaglomerular apparatus, and highly conserved capacities for concentrating diluting the urine. Plasma ANP values were paradoxically elevated (between 10 and 47 fmol/ml), despite the coexistence of intravascular volume depletion and increased plasma levels of renin and aldosterone. Although the patient had some clinical similarities to Bartter's syndrome, fractional sodium chloride (NaCl) reabsorption during hypotonic saline diuresis was normal and no clinical amelioration was observed while on indomethacin therapy. Neither a tumor nor cardiac or cerebral abnormalities, which could be responsible for the increased ANP secretion, were detected. These clinical, biochemical, and histological features have not been previously described together and may represent a new clinical syndrome. The pathophysiology of this entity remains unknown, but an attractive, although unproven, hypothesis is that the renal defect in NaCl reabsorption in this patient could be related to an inappropriate and unregulated secretion of ANP.

Topics: Aldosterone; Atrial Natriuretic Factor; Blood Volume; Child; Cyclooxygenase Inhibitors; Electrocardiography; Humans; Indomethacin; Kidney; Kidney Diseases; Male; Sodium; Sodium, Dietary; Syndrome; Water-Electrolyte Imbalance

The ability of atrial natriuretic peptide (ANP) to prevent cisplatin-induced nephrotoxicity was compared to the protective effect of 3% NaCl. ANP (1 microgram/kg/min), 3% NaCl or peptide buffer vehicle (50 microliters/min) were infused for 45 min to conscious unrestrained rats immediately after cisplatin administration (5 mg/kg i.v.). Measurements taken 72 h after drug treatment indicated that compared to animals receiving cisplatin only, ANP co-treated rats had lower post-treatment plasma creatinine concentrations (0.70 +/- 0.07 vs 1.3 +/- 0.17 mg/dl; P < 0.05), blood urea nitrogen (BUN) concentrations (44.2 +/- 5.8 vs. 65.5 +/- 2.1 mg/dl; P < 0.05) and higher post-treatment glomerular filtration rates (GFR) (0.71 +/- 0.18 vs. 0.14 +/- 0.03 ml/min; P < 0.05). ANP was as effective as 3% NaCl in preventing cisplatin nephrotoxicity in this model. The effect of ANP co-treatment on the anti-tumor activity of cisplatin was also examined using the Walker 256 carcinosarcoma model. ANP treatment did not result in any observable loss in anti-tumor activity. When ANP was administered 72 h after cisplatin treatment, improvement in GFR was observed for the duration of the infusion, confirming the beneficial effect of ANP on cisplatin-damaged kidneys. ANP may have a role in the treatment and prevention of cisplatin nephrotoxicity especially in clinical situations where treatment with a large fluid volume is contraindicated.

Topics: Animals; Antineoplastic Agents; Atrial Natriuretic Factor; Blood Urea Nitrogen; Carcinoma 256, Walker; Cisplatin; Creatinine; Drug Interactions; Glomerular Filtration Rate; Kidney; Kidney Diseases; Male; Rats; Rats, Sprague-Dawley; Renal Circulation; Sodium Chloride

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

A clinical and laboratory survey of systemic lupus erythematosus was conducted in 33 Arab patients in the UAE. Arthropathy (91%) followed by renal involvement (54%) and haematological disorders (45.5%) were the major clinical manifestations. Discoid rash (3%) was the least common. Apart from headaches, other neuropsychiatric symptoms were uncommon or not encountered. A number of distinctive clinical subsets of lupus was also observed. An unusually high prevalence of dsDNA antibodies was detected in the study (97%), compared with a prevalence of 89.5% of ANF. There was a relative paucity of anti-Ro (18.5%), La (7.5%) and RNP (11%) antibodies, but a high rate of anti-Sm(33%). The occurrence of the latter in patients with central nervous system and renal disease was insignificant. C3-Hypocomplementaemia occurred in 38.5% of the patients and a positive VDRL and Coomb's test in 9% and 24%, respectively. This study provides additional information on the characterization of systemic lupus erythematosus in various populations.

Topics: Adolescent; Adult; Antibodies; Antibodies, Antinuclear; Arabs; Atrial Natriuretic Factor; Autoantigens; Central Nervous System Diseases; Complement C3; Coombs Test; Female; Hematologic Diseases; Humans; Joint Diseases; Kidney Diseases; Lupus Erythematosus, Systemic; Male; Middle Aged; Ribonucleoproteins, Small Nuclear; Skin Diseases; snRNP Core Proteins; United Arab Emirates

This paper deals with the recent concept that the effectiveness of coupling between filtration and reabsorption is influenced by local and circulating hormones and by renal sympathetic nerves. The evidence supports a view of the proximal tubule as being an important regulator of extracellular fluid composition and blood pressure.

Topics: Absorption; Angiotensin II; Animals; Atrial Natriuretic Factor; Biological Transport; Endothelins; Humans; Kidney Diseases; Kidney Tubules, Proximal; Norepinephrine; Sodium

We investigated the localization and density of atrial natriuretic peptide (ANP) receptors in human renal biopsy specimens by using in vitro micro-autoradiography (ARG) of [125I]-alpha-human (1-28) ANP. In a preliminary study, we measured the effect of storing tissue samples on ANP binding, using in vitro micro-ARG of Wistar rat kidney under optimal conditions. Duration of the preservation period did not affect ANP binding to renal tissue until samples had been stored at -30 degrees C for two years. A total of 11 human renal tissues were used to assay binding of ANP-ARG, including normal tissue obtained after nephrectomy because of renal cancer. ANP binding occurred predominantly within the glomerulus and, to a lesser extent, in the tubular region both in rat kidney sections and in human renal biopsy specimens. The density of ANP binding, calculated by counting grains in fixed areas, was compared with normal and pathological tissues. The density of grains tended to decrease in patients with renal dysfunction and hypertension except for one case of IgA nephropathy with normal renal function and blood pressure. The density of grains increased in a patient with nephrogenic diabetes insipidus. In the present study, we have established a method that uses in vitro micro-ARG for assessing ANP binding in human biopsy specimens.

Topics: Animals; Atrial Natriuretic Factor; Autoradiography; Biopsy; Humans; Iodine Radioisotopes; Kidney; Kidney Diseases; Rats; Rats, Wistar; Receptors, Atrial Natriuretic Factor

Topics: Atrial Natriuretic Factor; Blood Preservation; Cryopreservation; Heart Diseases; Humans; Hypertension; Kidney Diseases; Specimen Handling

Circulating immunoreactive atrial natriuretic peptide, IrANP(99-126) and the N-terminal fragment of the prohormone, IrANP(1-98) were measured in two population samples from the general population of Gothenburg, Sweden. A group of 85-year olds (974 subjects) and a group of 40-year olds (191 subjects) were investigated in respect of cardiovascular, renal and metabolic disease. IrANP(99-126) and IrANP(1-98) were significantly higher in the 85-year olds compared to the 40-year olds, and were significantly increased in subjects with congestive heart failure, ischaemic heart disease, atrial fibrillation and renal dysfunction but not in subjects with hypertension. Eighty-five-year-old subjects who were on treatment with digitalis, beta-adrenergic-blockers, nitrates and diuretics had significantly increased IrANP(99-126) and IrANP(1-98). In multivariate analysis IrANP(99-126) concentrations were predictive for congestive heart failure, ischaemic heart disease, atrial fibrillation and treatment with beta-blockers and anti-depressant drugs. IrANP(1-98) was predictive for congestive heart failure, ischaemic heart disease, atrial fibrillation, diabetes mellitus, renal failure and drug treatment with beta-blockers and neuroleptics. We conclude that measurements of circulating concentrations of IrANP(99-126) and/or IrANP(1-98) may add valuable information in the diagnosis of congestive heart failure and ischaemic heart disease in an elderly population. It remains to be determined whether routine measurements of circulating IrANP (99-126) and IrANP(1-98) may be of value in predicting current cardiovascular disease for the individual patient.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Cardiovascular Diseases; Female; Heart Diseases; Humans; Kidney Diseases; Male; Metabolic Diseases; Peptide Fragments; Protein Precursors

Cyclosporin A has markedly improved graft survival in transplant patients but its side effects, such as renal toxicity and hypertension, pose management problems in transplant recipients. This toxicity has been attributed to prostaglandin inhibition. Concurrent administration of misoprostol (a prostaglandin E1 analog) prevents chronic cyclosporin A-induced nephrotoxicity but not hypertension in rats.

Topics: Aldosterone; Animals; Atrial Natriuretic Factor; Blood Pressure; Chronic Disease; Creatinine; Cyclosporine; Drug Therapy, Combination; Electrolytes; Glomerular Filtration Rate; Heart Rate; Hypertension; Kidney Diseases; Misoprostol; Osmolar Concentration; Prostaglandins; Rats; Rats, Sprague-Dawley; Renal Circulation; Renin

Seven-month-old, lean male SHHF/Mcc-cp rats, a model of spontaneous hypertension, progressive renal dysfunction, and congestive heart failure (CHF), were treated with either clonidine (CL) or enalapril (EN) or received no treatment (CON) for 20 weeks. CL significantly decreased systolic blood pressure (SBP), kidney weights, and severity of renal lesions as compared with untreated CON. EN produced a decrease in SBP comparable to that in CL. Kidney weights and severity of renal histologic changes in the EN group were intermediate between those of the CL and CON groups. Despite similar plasma atrial natriuretic peptide (ANP) concentrations, CL treatment resulted in a significant increase in the density of guanylate cyclase-linked glomerular ANP receptors, whereas EN treatment resulted in a significant decrease in the total number of ANP receptors and in the number of nonguanylate cyclase-linked receptors and an increase in overall binding affinity. These findings demonstrate that antihypertensive agents will slow progression of renal injury in SHHF/Mcc-cp rats and that CL is more effective than EN in alleviating progressive kidney damage in this model. Furthermore, different classes of antihypertensive drugs may alter the density or ratio of biologically active and clearance ANP receptor sites in the glomerulus.

Topics: Animals; Atrial Natriuretic Factor; Binding Sites; Clonidine; Cyclic GMP; Enalapril; Hypertension; Hypertrophy; Kidney; Kidney Diseases; Kidney Glomerulus; Male; Rats; Rats, Inbred Strains; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Atrial Natriuretic Factor; Heart; Heart Failure; Humans; Kidney; Kidney Diseases; Renin-Angiotensin System

This study was undertaken to investigate circulating endothelin (ET) and associated renal hemodynamics in the acute ischemic renal dysfunction associated with suprarenal aortic cross-clamping (ACC) in the presence and absence of prostaglandin inhibition in the anesthetized dog. Second, the modulating action of exogenous atrial natriuretic factor (ANF) was also investigated. In Group I (ACC; N = 6), ACC was performed in the absence of prostaglandin inhibition. No change in mean arterial pressure, GFR, RBF, renal vascular resistance, or ET was noted 2 h after reperfusion when compared with baseline values. In the presence of prostaglandin inhibition with indomethacin (10 mg/kg iv) (Group II, ACC + INDO; N = 10), an increase in plasma ET was first noted to be elevated above baseline ET in Group I as well as during and 2 h after ACC in association with a reduction in GFR, marked renal vasoconstriction, and a sustained increase in arterial pressure. To evaluate the role of the kidney in this increase in ET, another group (Group III, ACC + INDO + NEPH; N = 6) was investigated in the presence of prostaglandin inhibition, and bilateral renal artery clamping was performed 30 min before ACC and maintained throughout the protocol to simulate nephrectomy. In this group, plasma ET concentrations did not increase during ACC. Because ANF may antagonize the renal actions of ET in vivo and may suppress ET release in vitro, the action of ANF upon GFR and plasma ET was evaluated in Group IV (ACC + INDO + ANF; N = 6).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Aorta, Thoracic; Atrial Natriuretic Factor; Blood Pressure; Constriction; Dogs; Endothelins; Glomerular Filtration Rate; Ischemia; Kidney; Kidney Diseases; Vascular Resistance

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

ANP administered to cirrhotic dogs or chronic caval dogs with ascites and urinary sodium retention (USR) usually causes heterogeneity of natriuretic response. To assess whether this same phenomenon would occur in the absence of edema, ANP at 100 ng/kg/min was given to dogs before and after the induction of USR by a variety of techniques. Eight dogs were over-diuresed with furosemide over a 2-day period, and 9 dogs were subjected to subacute hemorrhage over a similar period. These dogs were retested with ANP one day later. All 8 dogs given furosemide showed no response to ANP (delta UNa V = 7.4 +/- 4.8 microEq/min), compared to a normal response prior to the diuretic (delta UNa V = 128 +/- 34 microEq/min). The 9 hemorrhaged dogs also responded normally to ANP prior to this manipulation (delta UNa V = 74 +/- 14 microEq/min), but a blunted response post-hemorrhage (delta UNa V = 35 +/- 13 microEq/min). This profile was made up of 5 dogs who responded to ANP (delta UNaV = 62 microEq/min) and 4 who had no response whatsoever (delta UNa V = 3 microEq/min). When 8 dogs were given USR because of continuous mineralocorticoid administration, none responded, but all had a magnified natriuretic response to ANP during the 'escape' phase. Eight dogs were administered minoxidil (10 mg) by mouth daily to induce USR. All 8 dogs responded to ANP (delta UNa V = 93 +/- 6 microEq/min) which was no different from the pretreatment response (delta UNa V = 65 +/- 3 microEq/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Atrial Natriuretic Factor; Dogs; Edema; Female; Fludrocortisone; Furosemide; Glomerular Filtration Rate; Hemorrhage; Kidney Diseases; Male; Minoxidil; Natriuresis

In anesthetized rats we tested the hypothesis that amphotericin B (AmB) reduces glomerular filtration rate (GFR) by activating the tubuloglomerular feedback (TGF) mechanism. Infusion of 1 mg/kg AmB over 50 min was followed by a reduction in kidney GFR (from 0.47 +/- 0.03 to 0.39 +/- 0.02 ml/min per 100 g body wt during the second hour after infusion; P less than 0.05) and by an increase in urine flow and urinary chloride excretion. Single-nephron GFR (SNGFR) measured in proximal (TGF interrupted) or distal tubules (TGF intact) decreased to a similar degree from 33.4 +/- 1.8 and 30.6 +/- 1.2 nl/min in the control period to 19.7 +/- 1.9 and 21.2 +/- 1.6 nl/min during the second hour after AmB infusion (P less than 0.05). Distal chloride concentrations and TGF responses to changes in loop of Henle flow rate were not significantly altered by AmB. AmB at 10(-5) M reduced the diameter of isolated perfused afferent arterioles from rabbit kidneys. In isometrically contracting rings of rabbit aorta and renal artery in vitro AmB produced endothelium-independent constriction, with half-maximal contraction (EC50) being achieved by 1.8 x 10(-6) and 2.6 x 10(-6) M in intact vessels and 1.3 x 10(-6) and 1.7 x 10(-6) M in endothelium-denuded vessels respectively. Tension development did not occur in Ca-free media or in the presence of Ca channel blockers. Pretreatment with ouabain or Bay K 8644 potentiated the effect of AmB. The vasoconstrictive effect of AmB was counteracted by aminophylline and atrial natriuretic peptide. We conclude that the AmB-induced reduction in GFR is not caused by TGF activation and that AmB has a direct vasoconstrictor effect that is probably initiated by depolarization-induced opening of Ca channels. This effect may be an important component of the nephrotoxic actions of AmB.

Topics: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; Amphotericin B; Animals; Aorta; Arterioles; Atrial Natriuretic Factor; Calcium; Calcium Channels; Glomerular Filtration Rate; In Vitro Techniques; Inulin; Kidney Diseases; Male; Metabolic Clearance Rate; Muscle, Smooth, Vascular; Ouabain; Phentolamine; Rats; Rats, Inbred Strains; Renal Artery; Sodium Chloride; Theophylline; Vasoconstriction

We have localised atrial natriuretic factor (ANF) in the human kidney by immunocytochemistry and radioimmunoassay. ANF is specifically visualised in the distal convoluted tubule cells and the intercalated cells of the connecting tubules and collecting ducts of the human nephron. The number of immunoreactive cells and tissue values for the peptide were compared between samples from normal kidneys and biopsies obtained from hypertensive patients, in whom the tissue ANF immunoreactivity was found to be reduced. Specific experiments are necessary to establish whether renal ANF is synthesised de novo or captured through endocytosis by the renal tubular cells. The possible functional roles of renal ANF are discussed.

Topics: Aged; Antibodies; Atrial Natriuretic Factor; Biopsy; Female; Humans; Immunoenzyme Techniques; Kallikreins; Kidney; Kidney Diseases; Kidney Tubules; Male; Middle Aged; Nephrons; Proteins

The effects of atrial natriuretic peptide (ANP) on urinary protein excretion were examined in patients with renal parenchymal diseases (RPD, n = 18) and those with diabetes mellitus (DM, n = 12). Before and 30 min after intravenous injection of ANP (50 micrograms), urine samples were collected. ANP injection increased urinary volume and urinary sodium excretion in both groups. In RPD, urinary protein excretion (UprV) increased by 87% (1.5 +/- 0.7 [SEM] to 2.8 +/- 1.1 mg/min, p less than 0.05). ANP also increased UprV in patients with diabetic nephropathy [N(+); 1.7 +/- 0.8 to 5.0 +/- 2.5 mg/min, p less than 0.05] and those without nephropathy [N(-); 0.10 +/- 0.02 to 0.22 +/- 0.07 mg/min, p less than 0.05]. Since ANP increased creatinin clearance in both groups (+9.4 +/- 2.5 ml/min in RPD and +24.1 +/- 3.5 ml/min in DM, p less than 0.01 for both), urinary protein to creatinine excretion ratios (UprV/UcrV) were determined, which should be a parameter of glomerular protein permeability. The UprV/UcrV ratio increased by 48% (p less than 0.01) and 24% (p less than 0.05) in RPD and in DM, respectively. ANP did not change urinary composition of albumin and globulin. In RPD, increases in UprV by ANP were positively related to the basal serum creatinin levels (r = 0.57, p less than 0.01). In DM group, ANP-induced increases in the UprV/UcrV ratio were higher in the N(+) subgroup than in the N(-) subgroup (+0.8 +/- 0.4 vs +0.09 +/- 0.04, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Atrial Natriuretic Factor; Diabetes Mellitus; Female; Humans; Kidney Diseases; Male; Middle Aged; Proteinuria

The acute renal effects of systemic hypoxemia and the ability of atrial natriuretic peptide (ANP) to reverse these effects were assessed in seven anesthetized and mechanically ventilated adult rabbits. Throughout the experiment, arterial pH, PaCO2 and HCO3 remained unchanged. Hypoxemia induced a significant increase in rabbit-ANP plasma levels from 151 +/- 26 to 246 +/- 65 pg/ml. During the normoxemic period (PaO2 = 131 +/- 12 mm Hg), glomerular filtration rate (GFR), renal blood flow (RBF), renal vascular resistance (RVR) and urinary sodium excretion (UNaV) were similar in both kidneys. The subsequent hypoxemic period (PaO2 = 30 +/- 1 mm Hg) caused a decrease in right and left kidney function: GFR, -26 +/- 5 and -29 +/- 6%; RBF, -17 +/- 9 and -29 +/- 8%; RVR, +28 +/- 16 and +59 +/- 30%; urine flow rate, -38 +/- 6 and -36 +/- 6%; and UNaV, -51 +/- 7 and -50 +/- 7%, respectively. Human-ANP infusion in the left renal artery (100 ng/min) during sustained systemic hypoxemia induced a significant improvement in GFR (+57 +/- 18%), RBF (+21 +/- 8%), RVR (-20 +/- 7%), urine flow rate (+151 +/- 27%) and UNaV (+270 +/- 48%) in the left experimental kidney, as compared with the preceding hypoxemic period. In contrast, the function of the right control kidney remained impaired.

Topics: Animals; Atrial Natriuretic Factor; Hemodynamics; Hypoxia; Infusions, Intravenous; Kidney Diseases; Kidney Function Tests; Rabbits

Concentrations of human atrial natriuretic peptide-like immunoreactivity (hANP-LI) were measured by a highly sensitive and specific radioimmunoassay (Biochem Biophys Res Commun 1986;137:231-6) in normal subjects and in renal disease patients without accompanying congestive heart failure, hypertension, edema, diabetes, or pregnancy. We attempted to clarify whether the hANP-LI concentration in plasma was increased by loss of renal mass. We found no correlation between the hANP-LI concentration in plasma and creatinine clearance (Ccr, 4.6-122.3 mL/min) in patients with renal disease (n = 63, r = -0.196), nor between hANP-LI concentrations in plasma and urine (n = 97, r = -0.207). The fractional excretion of hANP (FEhANP) correlated significantly with Ccr (n = 63, r = 0.520, P less than 0.01) and with FENa (n = 35, r = -0.503, P less than 0.01). Increased FEhANP in patients with chronic renal failure may have resulted because of an increase in single-nephron glomerular filtration rate similar to the FENa increase in these patients. The present data indicate that decreased renal function itself does not increase the concentration of hANP-LI in plasma.

Topics: Adolescent; Adult; Aged; Atrial Natriuretic Factor; Female; Glomerular Filtration Rate; Humans; Kidney Diseases; Male; Middle Aged

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Cyclosporins; Diuresis; Glomerular Filtration Rate; Kidney Diseases; Male; Natriuresis; Potassium; Rats; Rats, Inbred Strains

The case of a 7-year-old boy with the normotensive form of "chloride-shunt" syndrome is described. An unusual feature was the clinical presentation with lithiasis, caused by marked hypercalciuria of renal origin. The present studies were carried out to investigate the nature of the renal tubular defect. Indices for proximal and distal sodium chloride reabsorption were increased during hypotonic saline diuresis. Baseline sodium chloride excretion was low but increased above the range of control values after acute furosemide administration. Baseline potassium excretion was low, was not modified by the infusion of sodium chloride and increased significantly during infusions of sodium sulphate or sodium bicarbonate. Calcium excretion remained unchanged during sodium chloride, sodium sulphate or sodium bicarbonate infusions, but increased after furosemide administration. Nasal insufflation of 1-desamino-8-D-arginine-vasopressin induced both an increase in potassium excretion and a decrease in calcium and magnesium excretion. Plasma atrial natriuretic peptide was increased and was not significantly modified by infusion of hypertonic saline or acute administration of furosemide. These findings indicate that the primary renal abnormality appears to be an enhanced tubular reabsorption of sodium chloride, apparently present in the proximal tubule and the ascending loop of Henle. The associated presence of hypercalciuria also suggests a transport defect in the distal tubule. Decreased potassium excretion probably depends on a voltage-shunting defect in the cortical collecting tubule, which can be reversed by increasing the delivery of non-reabsorbable anions or by enhancing the conductance of the luminal membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Atrial Natriuretic Factor; Calcium; Chlorides; Humans; Hydrochlorothiazide; Infant; Kidney; Kidney Diseases; Kidney Tubules; Male; Potassium; Sodium Chloride; Syndrome

Human renal biopsies are currently used to provide information about morphologic changes, chronicity of disease, patterns of inflammation, and immunoglobulin deposition. This practice has provided only limited insight into functional aberrations and has failed to provided information necessary for disease classification based on pathophysiology. To expand the potential of the renal biopsy in this regard and to determine whether differences in glomerular atrial natriuretic factor (ANF) binding exist in different forms of primary renal disease, quantitative autoradiography and 125I-human ANF (1-28) were used to determine the location and pharmacological characteristics of ANF binding sites in the normal human kidney. Specific ANF binding was highest in the glomeruli, but lower levels of specific binding were localized to the inner medulla and the interlobular arteries. ANF binding sites in the human kidney were found to be highly stable and similar in both location and pharmacology to those observed in experimental animals. As determined by saturation experiments, the equilibrium dissociation constants for glomeruli, inner medulla, and interlobular arteries were almost identical at 4.0 x 10(-11) mol/L. Competitive binding inhibition studies with unlabeled human ANF (1-28) demonstrated highly specific binding shared by the glomerulus, inner medulla, and interlobular artery, with apparent half-maximal inhibition concentrations of 9.2 x 10(-10) mol/L, 8.0 x -10 mol/L, and 8.2 x 10(-10) mol/L, respectively. Quantitation of specific binding of ANF to glomeruli in needle biopsy specimens of three primary glomerulopathies, ie, minimal-change disease, membranous nephropathy, and focal glomerulosclerosis, showed no differences among the groups. This study demonstrates the feasibility of studying receptor physiology on biopsy specimens of the human kidney and should allow renal diseases, particularly of glomerular origin, to be characterized according to differences in hormone binding and hormone responsiveness. The absence of significant differences in glomerular ANF binding in the primary glomerulopathies studied is consistent with other studies that have failed to delineate important pathophysiological differences in renal function and volume homeostasis in these disease states.

Topics: Atrial Natriuretic Factor; Autoradiography; Binding, Competitive; Biopsy, Needle; Humans; Kidney; Kidney Diseases; Kidney Glomerulus; Ligands; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface; Time Factors; Tissue Distribution

In 14 patients with arterial hypertension secondary to chronic renal parenchymal disease and impaired renal function, 24-h ambulatory and casual blood pressure readings plasma, angiotensin II, aldosterone, arginine vasopressin and atrial natriuretic peptide, creatinine clearance, plasma lipids and lipoproteins, and body weight were determined after consecutive 3-week periods on placebo and sustained release verapamil 240 mg/day. Verapamil reduced the mean 24-h ambulatory blood pressure from 152/104 to 142/97 mm Hg. Blood pressure was significantly reduced during the daytime and the evening, but not at night. Casual blood pressure was also significantly reduced from 176/106 mm Hg to 154/96 mm Hg. No significant changes were found in the hormones, creatinine clearance, plasma lipids and lipoproteins, heart rate or body weight. The atrial natriuretic peptide level was significantly correlated with the calculated creatinine clearance (r = -0.797). Thus, sustained release verapamil 240 mg as a single daily dose had a moderate hypotensive effect in patients with chronic renal disease without inducing tachycardia, activation of the renin-angiotensin-aldosterone system, or increasing body weight, and without altering renal function and plasma lipids and lipoproteins. The negative correlation between atrial natriuretic peptide and glomerular filtration rate supports the hypothesis that the extracellular volume increases during progression of renal disease.

Topics: Adult; Aldosterone; Angiotensin II; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Chronic Disease; Delayed-Action Preparations; Female; Humans; Hypertension, Renal; Kidney Diseases; Male; Middle Aged; Verapamil

Topics: Animals; Atrial Natriuretic Factor; Cyclosporins; Goats; Hypertension; Kidney Diseases

Functional renal failure of cirrhosis (FRFC) is a usually fatal syndrome of acute renal failure occurring in patients with advanced liver disease. Although not conclusively proven, most evidence suggests that renal arterial and arteriolar vasoconstriction is the cause of the renal failure in these patients. However, the mediators of the vasoconstriction remain unknown. Human atrial natriuretic factor (hANF) is a hormone with potent natriuretic, diuretic, and vasorelaxant properties. A deficiency of hANF could lead to renal arterial vasoconstriction and avid renal sodium retention as seen in FRFC. This study was undertaken to determine if patients with FRFC are deficient in circulating hANF. Seven patients with advanced alcoholic liver disease and renal failure of unknown cause (FRFC) were compared with 7 patients with advanced alcoholic liver disease, ascites, and normal serum creatinine as well as with 14 healthy volunteers. Plasma hANF was measured by radioimmunoassay. Plasma hANF was 742 +/- 227 pg/ml (mean +/- SEM) in patients with FRFC compared with 360 +/- 70 pg/ml in patients with liver disease and normal serum creatinine (p greater than 0.05) and 28 +/- 5.7 pg/ml in healthy volunteers (p less than 0.005 vs. FRFC and chronic liver disease, ascites, and normal serum creatinine). Thus, FRFC is not caused by a deficiency of circulating hANF. The elevated plasma hANF levels in patients with chronic liver disease and continued sodium retention may suggest a renal insensitivity to the natriuretic effects of hANF.

Topics: Adult; Atrial Natriuretic Factor; Creatinine; Female; Hepatorenal Syndrome; Humans; Kidney Diseases; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Radioimmunoassay

Regulation of renal excretion of atrial natriuretic peptide (ANP) was studied in kidney disease patients and healthy kidney donors. The measured ANP concentration in the patient's plasma did not correlate with their creatinine clearance (Ccr), while the fractional excretion of ANP (FEANP) significantly correlated with Ccr. FEANP in healthy persons is less than 1%. In the healthy donors of kidneys for transplantation, approximately 80% of the plasma ANP from the renal artery appeared in the renal vein. From these results, this high recovery of ANP in the veins does not appear to be adequately explained by its degradation in the renal arterioles and nephrons. The FEANP from kidney disease patients significantly correlated with FENa, FEK and FEP, but not with FECa and FEMg. The manner of ANP handling in the nephron may possibly differ from that of Ca or Mg.

Topics: Adolescent; Adult; Aged; Atrial Natriuretic Factor; Female; Humans; Kidney; Kidney Diseases; Male; Middle Aged

We have reported that the renin response to systemic hypotension is inhibited in the presence of elevated atrial pressure and that elevations in atrial pressure of similar or larger magnitude cause graded increases in plasma atrial natriuretic peptide (ANP). Therefore we tested the hypothesis that comparable increments in plasma ANP can inhibit renal hypotension-induced increases in plasma renin activity (PRA) in conscious dogs. Renal perfusion pressure was controlled using cuffs implanted around the abdominal aorta just above the renal arteries. Reducing renal perfusion pressure by 10 or 30% of control caused graded increases in PRA (P less than 0.01). Infusion of 1-28 rat ANP (5 ng X kg-1 X min-1), which increased plasma ANP by 34.8 +/- 7.5 (SE) pg/ml, eliminated increases in PRA in response to a 10% reduction in renal perfusion pressure and markedly inhibited the response to a 30% pressure reduction (P less than 0.01). These results indicate that increments in plasma ANP which reproduce endogenous release inhibit renal hypotension-induced stimulation of PRA. Furthermore, the results provide an explanation for the inhibition of the renin response to renal hypotension during elevated atrial pressure.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Dogs; Hypotension; Kidney Diseases; Renin

Molecular forms of atrial natriuretic polypeptides circulating in human plasma were analyzed by chromatographic separation, coupled with radioimmunoassay. Analyses were done with human plasma samples taken from 24 human subjects, divided into groups of healthy volunteers, patients with renal disease, and patients with heart disease, with 8 subjects in each group. Although alpha-hANP was found as a major circulating form in most of the plasma specimens (16 cases), beta-hANP accompanied by alpha-hANP was found in 6 cases including 2 healthy volunteers. In addition, hANP-immunoreactive macromolecule, which is likely a bound form of hANP, was found to some extent in all the specimens tested. Diversity of human plasma in ANP molecular distribution was discussed in connection with a radioimmunoassay for plasma ANP.

Topics: Atrial Natriuretic Factor; Cross Reactions; Heart Diseases; Humans; Kidney Diseases; Molecular Weight

To test the effect of exogenous atrial natriuretic factor (ANF) on the kidney function of rats with chronic renal insufficiency, we examined the responses to bolus infusions of atriopeptin III in two models of renal insufficiency, namely, nephrosclerosis and glomerulonephritis. Hypertensive Dahl S rats receiving a high (8%) NaCl diet for 12 weeks, and rats with anti-glomerular basement membrane nephritis, both of which had glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) less than half those of respective control rats, exhibited similar relative increases In GFR and ERPF in response to atriopeptin III as did controls. Natriuresis, diuresis, and decreased blood pressure were as prominent in rats with either form of renal disease as in control rats. Rats receiving high NaCl intake, irrespective of renal function, had relatively exaggerated responses compared with rats receiving a normal NaCl diet. We conclude that rats with chronic renal insufficiency of diverse causes respond briskly to ANF despite presumed hyperperfused and hyperfiltering nephrons. Thus, diseased kidneys exhibit substantial renal functional "reserve." The renal response to ANF appears to be influenced by NaCl intake in both normal animals and those with renal insufficiency.

Topics: Animals; Atrial Natriuretic Factor; Glomerular Filtration Rate; Kidney; Kidney Diseases; Male; Rats; Rats, Inbred Strains

A sensitive and specific procedure for the measurement of atrial natriuretic peptide (ANP) in human plasma by radioreceptor assay, using bovine adrenal membranes treated with Triton-X-100, is described. Plasma levels (mean +/- SEM) of ANP in healthy subjects on a normal sodium intake were 8.4 +/- 1.4 pg/ml and could be modified by changes in sodium intake with increases in sodium intake being associated with higher levels. Mean plasma ANP was approximately 2-fold higher in patients with essential hypertension and 4-fold higher in patients with cardiac or renal disease. The values obtained were comparable in magnitude to those obtained by radioimmunoassay and there was a strong correlation (r = 0.94; p less than 0.001) between the values obtained by radioimmuno- and radioreceptor-assay. These results suggest that circulating ANP corresponds to the biologically active peptide and point to an important role of the atrial peptides in the control of sodium balance.

Topics: Adult; Aged; Atrial Natriuretic Factor; Female; Heart Diseases; Humans; Hypertension; Kidney Diseases; Male; Middle Aged; Radioimmunoassay; Radioligand Assay; Reference Values; Sodium

Using a radioimmunoassay for atrial natriuretic peptide (ANP) we studied plasma concentrations of immunoreactive ANP in order to investigate the pathophysiological role of ANP in patients with various diseases. Plasma ANP levels were elevated in patients with congestive heart failure (394 +/- 260 pg/ml, n = 8) and chronic renal failure (219 +/- 86 pg/ml, n = 11). In patients undergoing hemodialysis plasma ANP levels were markedly high and decreased after hemodialysis from 433 +/- 166 pg/ml to 204 +/- 92 pg/ml (n = 11). ANP was removed from blood to dialysate (21 +/- 13 pg/ml of dialysate, n = 6, dialysate flow: 500 ml/min). Plasma ANP level was conversely correlated with creatinine clearance (r = -0.812, p less than 0.001) in patients with renal diseases (n = 29). In patients with atrial fibrillation, pace maker implantation, lung disease, chronic glomerulonephritis, nephrotic syndrome, essential hypertension, liver disease and cerebrovascular disease, plasma ANP levels were not significantly different from those in normal subjects (70 +/- 32 pg/ml, n = 28). These results suggest that ANP may be a circulating hormone playing pathophysiological roles in congestive heart failure and chronic renal failure.

Topics: Adult; Atrial Natriuretic Factor; Cardiovascular Diseases; Cerebrovascular Disorders; Chronic Disease; Female; Humans; Kidney Diseases; Liver Diseases; Lung Diseases, Obstructive; Male; Middle Aged; Radioimmunoassay; Renal Dialysis

The natriuretic action of the atrial natriuretic factor (ANF) was studied in massively proteinuric, anti-natriuretic and edematous nephrotic rats with moderate impairment of renal function. Animals were distributed among four groups: NA----NR, NV----NR, NeA----NR and NA----NeR, where normal atrial (NA) or normal ventricular (NV) or "nephrotic" atrial (NeA) extracts were injected (----) into normal rats (NR) or nephrotic rats (NeR). Control (C) clearance measurements were made before iv injection of the extracts and at four 15-min intervals thereafter (E). Mean arterial pressure and glomerular filtration rate did not change consistently in all four groups from the C to the E period. However, during the first 15-min period after extract injection, statistically significant fractional natriuretic peaks of 332, 361 and 662% of preinjection control values were demonstrable for the NA----NR, NeA----NR and NA----NeR groups, respectively, but not for NV----NR. Following the natriuretic peak, natriuresis returned to control values for NA----NR, but remained above control levels for the NeA----NR and NA----NeR groups. We conclude that, since both the atrial extract from nephrotic rats injected into normal rats and the atrial extract from normal rats injected into nephrotic rats elicited marked natriuresis, the anti-natriuretic edematous condition observed in nephrotic animals cannot be attributed either to the absence of ANF in their atria or to the unresponsiveness of their kidneys to ANF.

Topics: Animals; Atrial Natriuretic Factor; Edema; Glomerular Filtration Rate; Kidney Diseases; Male; Natriuresis; Nephrotic Syndrome; Rats; Rats, Inbred Strains; Sodium