atrial-natriuretic-factor and Renal-Insufficiency--Chronic

Midregional pro-atrial natriuretic peptide (MR-proANP), first isolated in 1981, is a novel peptide with multiple biological functions, especially within the cardiovascular system. This peptide plays an important role in many processes, including natriuresis, diuresis, and other physiological and pathophysiological pathways in the human body. Several electronic databases (PubMed, EBSCO, Scopus, and ScienceDirect) were analyzed in the present literature review. The aim of this study was to elucidate the wide roles of MR-proANP, which can be analyzed because of the development of a new sandwich immunoassay, and to determine the possible diagnostic and prognostic implications of MR-proANP on cardiovascular disease and other disorders. The studies discussed in this literature review provide valuable data on the role of ANP in the pathogenesis, diagnostic process, prognosis, and potential therapeutic strategies for disease. Although ANP is mainly associated with cardiovascular disease, it may be used as a biomarker in diabetology, neurology, and metabolic disorders.

Topics: Atrial Natriuretic Factor; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Obesity; Prognosis; Renal Insufficiency, Chronic

The pathologic consequences of sodium retention in the CKD population can lead to hypertension, edema, and progressive disease. Sodium excess is responsible for increases in oxidative stress, which alters kidney vasculature. As progression of CKD occurs, hyperfiltration by remaining nephrons compensates for an overall decrease in the filtered load of sodium. In the later stages of CKD, compensatory mechanisms are overcome and volume overload ensues. Nephrotic syndrome as it relates to sodium handling involves a different pathophysiology despite a common phenotype. Extrarenal sodium buffering is also examined as it has significant implications in the setting of advanced CKD.

Topics: Animals; Atrial Natriuretic Factor; Diet, Sodium-Restricted; Homeostasis; Humans; Hypertension; Nephrotic Syndrome; Oxidative Stress; Renal Insufficiency, Chronic; Renin-Angiotensin System; Skin; Sodium; Sympathetic Nervous System; Vasopressins

The incidence of renal complications including kidney failure is on the rise. Moreover, with aging of the population and the high incidence of diabetes, hypertension and obesity, this trend may prevail. An important cytoprotective enzyme that has been shown to improve renal function is heme-oxygenase (HO). HO is known to abate apoptosis and necrosis, and improves cell vitality, which in turn, may enhance tissue regeneration. Consistently, HO has been shown to restore tissue morphology by potentiating potentiate proteins of repair/regeneration and promoting neovascularization. The formation of new tissue may replace damaged or dysfunctional tissue to preserve cellular integrity and function after injury. Emerging evidence indicate that HO-inducers improve kidney function in several models including, (i) streptozotocin-induced diabetic rats, (ii) Zucker-diabetic-fatty rats, (iii) Zucker-fatty rats, (iii) spontaneously hypertensive rats, (iv) uninephrectomized deoxycorticosterone-acetate hypertensive rats, (v) N(ω)-nitro-l-arginine-methyl ester (L-NAME)-induced hypertensive rats, (vi) glycerol induced renal failure, (vii) nephrotoxic nephritis, (viii) sepsis-induced kidney injury, (ix) cystic renal disease, (x) cisplatin-mediated acute kidney injury, and (xi) rhabdomyolysis-induced renal injury. The mechanisms underlying the HO-mediated reno-protection include: (i) the restoration of renal morphology by enhancing proteins of regeneration, (ii) the potentiation of the HO-adiponectin-atrial natriuretic peptide axis, with corresponding suppression of oxidative/inflammatory insults and extracellular matrix/profibrotic factors, and (iii) the potentiation of podocyte cytoskeletal proteins such as nephrin, podocin, podocalyxin and CD2-associated-protein, which are fundamental for forming the glomerular filtration barrier that selectively allows small molecules to pass through but not large protein molecules. Thus, this review highlights the HO-adiponectin-atrial natriuretic peptide axis in renoprotection.

Topics: Adiponectin; Animals; Atrial Natriuretic Factor; Heme Oxygenase (Decyclizing); Humans; Kidney; Protective Agents; Renal Insufficiency, Chronic

This review discusses renal sodium handling in heart failure. Increased sodium avidity and tendency to extracellular volume overload, i.e. congestion, are hallmark features of the heart failure syndrome. Particularly in the case of concomitant renal dysfunction, the kidneys often fail to elicit potent natriuresis. Yet, assessment of renal function is generally performed by measuring serum creatinine, which has inherent limitations as a biomarker for the glomerular filtration rate (GFR). Moreover, glomerular filtration only represents part of the nephron's function. Alterations in the fractional reabsorptive rate of sodium are at least equally important in emerging therapy-refractory congestion. Indeed, renal blood flow decreases before the GFR is affected in congestive heart failure. The resulting increased filtration fraction changes Starling forces in peritubular capillaries, which drive sodium reabsorption in the proximal tubules. Congestion further stimulates this process by augmenting renal lymph flow. Consequently, fractional sodium reabsorption in the proximal tubules is significantly increased, limiting sodium delivery to the distal nephron. Orthosympathetic activation probably plays a pivotal role in those deranged intrarenal haemodynamics, which ultimately enhance diuretic resistance, stimulate neurohumoral activation with aldosterone breakthrough, and compromise the counter-regulatory function of natriuretic peptides. Recent evidence even suggests that intrinsic renal derangements might impair natriuresis early on, before clinical congestion or neurohumoral activation are evident. This represents a paradigm shift in heart failure pathophysiology, as it suggests that renal dysfunction-although not by conventional GFR measurements-is driving disease progression. In this respect, a better understanding of renal sodium handling in congestive heart failure is crucial to achieve more tailored decongestive therapy, while preserving renal function.

Topics: Atrial Natriuretic Factor; Diuretics; Glomerular Filtration Rate; Heart Failure; Humans; Kidney; Kidney Glomerulus; Kidney Tubules; Natriuretic Peptide, Brain; Renal Circulation; Renal Insufficiency, Chronic; Sodium; Water-Electrolyte Imbalance

To avoid perioperative cardiac complications and deterioration of renal function in chronic kidney disease (CKD), anesthesiologists are required to manage respiration and circulation properly. Three mechanisms are considered to worsen renal function during inappropriate mechanical ventilation; first, hypercapnia or hypoxemia, second, unstable systemic hemodynamic, and third, systemic inflammatory mediators derived from pulmonary biotrauma. Many circulatory problems are present in CKD patients, for example, hypertension, cardiac hypertrophy, cardiomyopathy, ischemic heart disease, arterial sclerotic valve disease, salt and water retention etc. Blood pressure in CKD patients should be controlled properly before surgery. Renal blood flow and renal perfusion pressure should be maintained by aggressive fluid therapy to avoid perioperative acute kidney injury (AKI) on CKD, while cardiac congestion should also be avoided. Perioerative renal protective effects of human atrial natriuretic peptide (hANP) on CKD still needs further investigation. Appropriate hemodynamic monitoring, including direct arterial pressure, left ventricular preload, intravascular volume and cardiac output could be helpful for anesthesiologists to manage CKD patients safely. In the area of CKD and anesthesia, there is lack of evidence in respiratory and circulatory strategies. Prospective studies in these aspects are required in the future.

Topics: Acute Kidney Injury; Atrial Natriuretic Factor; Cardiovascular Agents; Cardiovascular Diseases; Fluid Therapy; Hemodynamics; Humans; Monitoring, Intraoperative; Perioperative Care; Positive-Pressure Respiration; Postoperative Complications; Renal Insufficiency, Chronic; Respiration, Artificial

Chronic renal failure (CRF) is related to cardiac diseases. Cardiac surgery is also related to postoperative acute kidney injury (AKI). It means heart and kidney have close relationship. We analyzed recent published data to understand how to manage CRF patients undergoing cardiovascular surgeries. We compared endovascular surgery and open procedure for aortic aneurysm, especially about contrast media-related renal damage, On or Off CABG or PCI for ischemic heart disease. We also discussed the relation between cardiopulmonary bypass and AKI and the risk factors causing AKI after CPB. Finally, we discussed prevention and treatment options of CPB related AKI, including furosemide, hANP mannitol, and statin. Published evidence in this area is still insufficient, but many studies are still carried out focusing on postoperative AKI. In the future we may be able to find the best answer for managing CRF patients undergoing cardiovascular surgeries.

Topics: Acute Kidney Injury; Aortic Aneurysm; Atrial Natriuretic Factor; Cardiopulmonary Bypass; Cardiovascular Diseases; Cardiovascular Surgical Procedures; Contrast Media; Coronary Artery Bypass; Furosemide; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Mannitol; Myocardial Ischemia; Percutaneous Coronary Intervention; Perioperative Care; Postoperative Complications; Renal Insufficiency, Chronic; Thoracic Surgical Procedures

Chronic kidney disease (CKD) is an important risk factor for cardiac surgery. In the most recently reported NU-HIT trial for CKD with CKD patients underwent coronary artery bypass grafting (CABG) as subjects, carperitide was reported to be effective in terms of renal function. In the present study, a subanalysis was performed on patients registered in the NU-HIT trial for CKD from the standpoint of renin-angiotensin system, natriuresis and renal function.. 303 patients with CKD who underwent isolated CABG were divided into a group that received carperitide infusion and another group without carperitide. The renin activity, angiotensin-II, aldosterone, urine-sodium, urine- creatinine, fractional sodium excretion, renal failure index, and BNP levels.. There were significant lower in hANP group than the placebo group, in angiotensin-II at one day postoperatively, and in aldosterone from 0 day to one month postoperatively. FENa was significantly lower in the hANP group at 3 day and one week postoperatively.. In on pump isolated CABG patients with CKD, carperitide showed a potent natriuretic action and inhibited the renin-angiotensin system, suggesting that it prevented deterioration of postoperative renal function. Our findings raise new possibilities for the perioperative and postoperative management of patients undergoing surgery with cardiopulmonary bypass.

Topics: Atrial Natriuretic Factor; Biomarkers; Cardiopulmonary Bypass; Coronary Artery Bypass; Coronary Artery Disease; Double-Blind Method; Humans; Infusions, Parenteral; Japan; Kidney; Natriuresis; Renal Agents; Renal Insufficiency, Chronic; Renin-Angiotensin System; Time Factors; Treatment Outcome

Statins have beneficial effects on cardiovascular morbidity and mortality independently of reduction of plasma cholesterol.. In patients with type 2 diabetes and nephropathy, chronic kidney disease stage II-III, we tested the hypothesis that atorvastatin increased systemic and renal nitric oxide (NO) availability using L-NMMA as an inhibitor of NO production. We performed a randomized, placebo-controlled, crossover study, using atorvastatin/placebo treatment for five days with a standardized diet and fluid intake. We measured brachial BP (bBP), central BP (cBP), GFR, urinary output (OU), free water clearance (CH2O), fractional excretion of sodium (FENa), urinary excretion of albumin (UAER and UACR), AQP2 (u-AQP2) and ENaC (u-ENaCγ) and plasma concentrations of vasoactive hormones: renin, angiotensin II, aldosterone, arginine vasopressin, endothelin-1 and brain natriuretic peptide.. During atorvastatin and placebo treatment, L-NMMA infusion, changed the effect variables significantly, but to the same extent, i.e. an increase in bBP and cBP, and a decrease in GFR, OU, CH2O, FENa, u-AQP2 and u-ENaCγ. In addition, renin and angiotensin II was reduced, aldosterone increased, and vasopressin, endothelin-1 and brain natriuretic hormone unchanged.. During, atorvastatin and placebo treatment, inhibition of nitric oxide synthesis induced the same response in brachial and central blood pressure, GFR, renal tubular function and vasoactive hormones. Thus, atorvastatin did not change nitric oxide availability in type 2 diabetics with nephropathy.

Topics: Aged; Arginine Vasopressin; Atorvastatin; Atrial Natriuretic Factor; Blood Pressure; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glomerular Filtration Rate; Heart Rate; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney Tubules; Male; Middle Aged; Natriuretic Peptide, Brain; Nitric Oxide; omega-N-Methylarginine; Pulse Wave Analysis; Pyrroles; Renal Insufficiency, Chronic; Treatment Outcome; Vascular Stiffness; Vasopressins

Glomerular diseases (GD) lead to a variety of disorders of the vascular and the total body water volumes. Various pathomechanisms, including vascular underfill and overfill, have been suggested to explain these disturbances. Accordingly, the circulating renin-angiotensin-aldosterone system (cRAAS) is expected to be activated as either a cause or a result of these fluid disorders. The aim of this study was to characterize the activity of the cRAAS in dogs with GD and to evaluate its relationship with the vascular volume status. In a prospective study, we evaluated the plasma renin activity and the serum aldosterone concentration in 15 dogs with GD. Their fluid volume status was estimated with clinical variables reflecting volemia and hydration, echocardiographic volume assessment, N-terminal pro B-type natriuretic peptide, blood urea nitrogen:creatinine ratio, and the urinary fractional excretion of sodium. Ten dogs with chronic kidney disease (CKD) with matching degree of azotemia were recruited as controls. The activity of the cRAAS was low in 10 dogs, normal in 3 dogs, high in 1 dog and equivocal (high renin-low aldosterone) in 1 dog with GD. These dogs had a lower cRAAS activity than dogs with CKD (p = 0.01). The clinical evaluation showed 8 hypovolemic and 7 non-hypovolemic dogs; 3 dehydrated, 9 euhydrated and 3 overhydrated dogs. The cRAAS activity was not different between hypovolemic and non-hypovolemic dogs. The down-regulated cRAAS without obvious association with the clinical volume status of these dogs with GD, suggests different mechanisms of fluid volume dysregulation in dogs with GD than previously assumed. This finding however should be confirmed in a focused larger scale study, as it may influence the use of cRAAS blockers as part of the standard therapy of GD in dogs.

Topics: Aldosterone; Animals; Atrial Natriuretic Factor; Azotemia; Blood Urea Nitrogen; Dog Diseases; Dogs; Down-Regulation; Female; Glomerulonephritis; Male; Prospective Studies; Protein Precursors; Proteinuria; Renal Insufficiency, Chronic; Renin

Imbalance between anabolism and catabolism is linked to cachexia and protein-energy wasting (PEW), especially in frail populations such as patients with chronic kidney disease. PEW is responsible of poor outcomes with increased morbidity and mortality. Several causes are involved in PEW such as insulin resistance, acidosis, or hyperparathyroidism. Natriuretic peptides (NPs) have recently been described as activators of resting energy expenditure through the induction of browning of white adipose tissue in rodents with chronic kidney disease. The present study was therefore implemented to investigate whether NPs could be associated with PEW criteria and predict clinical outcomes.. We quantified serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) in a prospective cohort of 231 patients undergoing maintenance hemodialysis and atrial natriuretic peptide in a subgroup of 35 patients. Body composition parameters were measured with bioimpedance spectroscopy.. NT-proBNP was inversely associated with serum albumin, prealbumin, and body mass index and, conversely, positively associated with age and C-reactive protein. NT-proBNP as well as atrial natriuretic peptide were significantly higher in patients with PEW criteria. NT-proBNP was negatively associated with body fat mass. In multiple linear regression, NT-proBNP remained associated with body mass index. Kaplan-Meier analysis revealed a significant correlation between serum NT-proBNP concentrations and all-cause mortality and cardiovascular events. This association remained significant after multivariable Cox regression models adjusted for demographic factors and cardiovascular risk factors.. Accumulation of NPs seems to be associated with poor nutritional status and reduced survival among hemodialysis patients. Further studies are needed to confirm this association using resting energy expenditure measurement and adipose tissue biopsy.

Topics: Atrial Natriuretic Factor; Cachexia; Female; Humans; Male; Natriuretic Peptides; Prospective Studies; Renal Dialysis; Renal Insufficiency, Chronic

In this prospective study, we aimed to assess the haemodynamic changes before and after haemodialysis (HD) in cardiac healthy subjects on chronic HD by imaging methods and endocrine markers of fluid balance.. Mid-regional pro-atrial natriuretic peptide (MR-proANP), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), vasopressin (AVP) and copeptin (CT-proAVP), metanephrines and normetanephrines, renin and aldosterone, standard transthoracic echocardiography and diameter of vena cava inferior (VCID) were performed in 20 patients with end stage renal disease (CKD5D) before and after HD and were stratified in residual excretion (RE, less or more 0.5 l) and ultrafiltration rate (UF, less or more 2 l).. Copeptin was significantly higher in patients before HD. Copeptin was inversely correlated with haemodialysis treatment adequacy (KT/v), RE and UF, but was not significantly influenced by age, gender and body mass index (BMI). MR-proANP was significantly reduced by haemodialysis by 27% and was inversely correlated with KT/v, but there was a significant influence by UF, RE, age, gender and BMI. NT-proBNP was significantly higher in patients before HD and was not influenced by RE and UF. Renin, aldosterone, metanephrines and normetanephrines did not demonstrate significant differences. Echocardiographic parameters and VCID were significantly correlated with RE, UF and copeptin.. Modern biomarkers will provide cardiovascular risk assessment, but elimination (UF), RE and other factors may influence the serum concentrations, e.g. in patients with renal impairment. The interpretation will be limited by altered reference ranges, and will be restricted to individual courses combined with clinical and echocardiographic data.

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Biomarkers; Echocardiography; Female; Glycopeptides; Health Status; Humans; Male; Metanephrine; Middle Aged; Natriuretic Peptide, Brain; Normetanephrine; Peptide Fragments; Prospective Studies; Renal Dialysis; Renal Insufficiency, Chronic; Renin; Vasopressins; Vena Cava, Inferior

Recently, performance of cardiac surgery in hemodialysis patients has increased, but the mortality rate is high.. We retrospectively examined the early and long-term outcomes in 128 dialysis patients who underwent cardiac surgery with or without carperitide infusion and were followed for 2 years. Sixty-three patients received carperitide infusion during surgery and 65 patients did not.. The hospital mortality rate was 1.6% in the carperitide group and 12.3% in the non-carperitide group, being significantly lower in the carperitide group. The 2-year actuarial survival rate was 90.5% ± 3.7% in the carperitide group, and 76.9% ± 5.2% in the non-carperitide group, while the major adverse cardiovascular and cerebrovascular events (MACCE)-free rate at 2 years postoperatively was 90.5% ± 3.7% in the carperitide group and 67.7% ± 5.8% in the non-carperitide group.. These findings suggest that carperitide improves the early postoperative outcome in dialysis patients undergoing cardiac surgery, as has already been demonstrated in non-dialysis patients. An early postoperative cardioprotective effect of carperitide and improvement of renal function in oliguric patients might have contributed to this outcome. However, this was a retrospective study, so a prospective investigation is required to demonstrate the mechanisms involved. In addition, further evaluation of the long-term results would be desirable.

Topics: Aged; Atrial Natriuretic Factor; Cardiac Surgical Procedures; Disease-Free Survival; Drug Administration Schedule; Female; Hospital Mortality; Humans; Infusions, Parenteral; Kaplan-Meier Estimate; Male; Middle Aged; Postoperative Complications; Protective Agents; Renal Dialysis; Renal Insufficiency, Chronic; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome

We investigated the effectiveness of active renin-angiotensin-aldosterone system (RAAS) control with human atrial natriuretic peptide (hANP) and an angiotensin II receptor blocker (ARB) in patients with chronic kidney disease (CKD) undergoing coronary artery bypass grafting (CABG).. A total of 286 consecutive patients with CKD undergoing CABG were divided into three groups: Group C (n = 50) receiving placebo, the hANP group (n = 60) receiving hANP, and the active RAAS control therapy (ARC) group (n = 56) receiving hANP plus an ARB. Renal function, brain natriuretic peptide (BNP) and RAAS parameters were analyzed.. After 1 year, renal function parameters were better in the hANP and ARC groups compared with group C, and the dialysis rate was significantly lower (group C: 12%, hANP group: 1.7%, ARC group: 1.8%, p = 0.018) in the hANP and ARC groups. BNP levels were significantly lower in the hANP and ARC groups compared with group C (p = 0.001). There was also a significant difference of aldosterone among the groups (p = 0.023), as well as a significant difference between group C and the ARC group (p = 0.017).. The present study showed that active RAAS control preserved renal function in patients with CKD undergoing CABG. The improved early postoperative outcome with RAAS control may lead to long-term inhibition of cardiovascular events.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Atrial Natriuretic Factor; Coronary Artery Bypass; Coronary Artery Disease; Databases, Factual; Female; Humans; Japan; Kidney; Male; Middle Aged; Randomized Controlled Trials as Topic; Renal Dialysis; Renal Insufficiency, Chronic; Renin-Angiotensin System; Time Factors; Treatment Outcome

Proteinuria is a hallmark of chronic kidney disease (CKD) and cardiovascular disease (CVD), and a good predictor of clinical outcome. Selective endothelin A (ETA) receptor antagonist used with renin-angiotensin system (RAS) inhibitors prevents development of proteinuria in CKD. However, whether the improvement in proteinuria would have beneficial effects on CVD, independent of RAS inhibition, is not well understood. In this study, we investigated whether atrasentan, an ETA receptor antagonist, has renal and cardiovascular effects independent of RAS inhibition. Male Dahl salt sensitive (DSS) rats, at six weeks of age, received water with or without different doses of atrasentan and/or enalapril under high salt (HS) diet or normal diet (ND) for 6 weeks. At the end of 12th week, atrasentan at a moderate dose significantly attenuated proteinuria and serum creatinine without reducing mean arterial pressure (MAP), thereby preventing cardiac hypertrophy and improving cardiac function. ACE inhibitor enalapril at a dose that did not significantly lowered BP, attenuated cardiac hypertrophy while moderately improving cardiac function without reducing proteinuria and serum creatinine level. Nonetheless, combined therapy of atrasentan and enalapril that does not altering BP exerted additional cardioprotective effect. Based on these findings, we conclude that BP independent monotherapy of ETA receptor antagonist attenuates the progression of CKD and significantly mitigates CVD independent of RAS inhibition.

Topics: Animals; Atrasentan; Atrial Natriuretic Factor; Blood Pressure; Cardiomegaly; Disease Models, Animal; Echocardiography; Endothelin A Receptor Antagonists; Gene Expression; Heart Diseases; Hemodynamics; Hypertension; Hypertrophy; Kidney Function Tests; Male; Myocytes, Cardiac; Phenylephrine; Pyrrolidines; Rats; Receptor, Endothelin A; Renal Insufficiency, Chronic

Plasma levels of atrial and brain natriuretic peptides (ANP and BNP) are increased in patients with chronic kidney disease (CKD) complicated with deteriorated kidney function, but the relationship between the plasma level of ANP or BNP and the future development of CKD is unclear.. We measured the plasma ANP and BNP levels of 294 local residents without CKD in a Japanese community (56.5 ± 10.4 years, mean ± S.D.), who were followed up for the development of CKD over the next 7 years.. Sixty-three residents developed CKD during the follow-up period, and the baseline level of plasma ANP of these residents was significantly higher than in those without CKD development. Kaplan-Meier analysis showed that the residents with higher ANP than the median value developed CKD more frequently than those with lower ANP. The association between plasma ANP level and CKD development was found to be independent of baseline estimated glomerular filtration rate by a Cox proportional hazards model, while this association became insignificant when adjusted by age; plasma ANP was significantly correlated with age. Compared with ANP, the relationship between plasma BNP and CKD development was unclear in these analyses.. Age-related elevation of plasma ANP levels preceded the development of CKD in the general population of Japan, raising a possibility for ANP being involved in the development of CKD.

Topics: Adult; Age Factors; Aged; Atrial Natriuretic Factor; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Japan; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Proportional Hazards Models; Renal Insufficiency, Chronic; Risk Factors

The complex pathophysiological interactions between heart and kidney diseases are collectively known as cardiorenal syndrome. The renin-angiotensin system (RAS) may have a pivotal role in the development of cardiorenal syndrome. The aim of this study was to elucidate the RAS activity responsible for adverse post-infarction remodeling and prognosis in mice with renal failure. To establish the type IV cardiorenal syndrome model, 5/6 nephrectomy (NTX) was performed in a surgical procedure, followed by the induction of myocardial ischemia (MI) by a coronary artery ligation 4 weeks later. NTX and MI resulted in deteriorated left ventricular remodeling and RAS activation, which was improved by an aliskiren that appeared to be independent of renal function and blood pressure (BP). Moreover, MI induced in renin and angiotensinogen double-transgenic (Tg) mice showed comparable effects to MI plus NTX mice, including advanced ventricular remodeling and enhancement of RAS, oxidative stress, and monocytes chemoattractant protein (MCP)-1. Aliskiren suppressed these changes in the MI-induced Tg mice. In in vitro study, Nox2 expression was elevated by the stimulation of plasma from NTX mice in isolated neonatal cardiomyocytes. However, Nox2 upregulation was negated when we administered plasma from aliskiren-treated-NTX mice or isolated cardiomyocytes from AT1-deficient mice. Primary mononuclear cells also showed an upregulation in the expression of Nox2 and MCP-1 by stimulation with plasma from NTX mice. Our data suggest that renal disorder results in ventricular dysfunction and deteriorates remodeling after MI through excessive RAS activation. Moreover, renin inhibition improved the changes caused by cardiorenal syndrome.

Topics: Amides; Analysis of Variance; Animals; Atrial Natriuretic Factor; Chemokine CCL2; Disease Models, Animal; Fumarates; Humans; Hypertension; Kaplan-Meier Estimate; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Myocardial Infarction; Myocardium; Nephrectomy; Oxidative Stress; Renal Insufficiency, Chronic; Renin; Renin-Angiotensin System; Ventricular Remodeling

This study sought to determine the pharmacodynamic effect of modulation of volume status by withdrawal and reinstitution of diuretic treatment on markers of renal and tubular function.. Decreased renal perfusion and increased congestion are associated with renal dysfunction in patients with heart failure.. In this study, 30 patients with chronic systolic heart failure in a presumed euvolemic state and on standard oral furosemide therapy (40 to 80 mg) were examined. At baseline, subjects were withdrawn from their loop diuretics. After 72 h, their furosemide regimen was reinstated, and patients were studied again 3 days later. Serum creatinine, atrial and B-type natriuretic peptide, urinary kidney injury molecule (KIM)-1, urinary N-acetyl-beta-D-glucosaminidase (NAG), and serum as well as urinary neutrophil gelatinase-associated lipocalin (NGAL) were determined at various time points.. Diuretic withdrawal resulted in increases in atrial and B-type natriuretic peptide (both p < 0.05). Serum creatinine was unaffected. Both urinary KIM-1 (p < 0.001) and NAG (p = 0.010) concentrations rose significantly, after diuretic withdrawal, whereas serum and urinary NGAL were not significantly affected. After reinitiation of furosemide, both urinary KIM-1 and NAG concentrations returned to baseline (both p < 0.05), but NGAL values were unaffected.. Subclinical changes in volume status by diuretic withdrawal and reinstitution are associated with increases and decreases of markers of tubular dysfunction in stable heart failure. Diuretic therapy may favorably affect renal and tubular function by decreasing congestion.

Topics: Acetylglucosaminidase; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Comorbidity; Creatinine; Diuretics; Female; Furosemide; Heart Failure; Hepatitis A Virus Cellular Receptor 1; Humans; Kidney Function Tests; Kidney Tubules; Male; Membrane Glycoproteins; Natriuretic Peptide, Brain; Receptors, Virus; Renal Insufficiency, Chronic