natriuretic-peptide--c-type and Renal-Insufficiency

Congestion represents the primary reason for hospitalization of patients with heart failure and is associated with adverse outcomes. Fluid overload has been shown to be inadequately addressed in a significant subset of these patients in part due to lack of robust, reliable, and readily available biomarkers for objective assessment and monitoring of therapy. Natriuretic peptides have long been used in this setting, often in conjunction with other assessment tools such as imaging studies. Patients presenting with concomitant cardiac and renal dysfunction represent a unique population with regard to congestion in that the interactions between the heart and the kidney can affect the utility and performance of biomarkers of fluid overload. Herein, we provide an overview of the currently available evidence on the utility of natriuretic peptides in these patients and discuss the clinical conundrum associated with their use in the setting of renal dysfunction. We highlight the potential divergence in the role of natriuretic peptides for assessment of volume status in a subset of patients with renal dysfunction who receive renal replacement therapy and call for future research to elucidate the utility of the biomarkers in this setting.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Female; Heart Failure; Humans; Kidney; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Prognosis; Renal Insufficiency; Renal Replacement Therapy

In the last three decades many members of the natriuretic peptide family was isolated. The function and physiological role of these peptides are pleiotropic. All natriuretic peptides are synthesized from polypeptide precursors. Together with the sympathetic nervous system and other hormones they play key roles, like an endogenous system in the regulation of the body fluid homeostasis and blood pressure. Changes in this balance lead to dysfunction in the endothel and left ventricle, which can cause severe complications. In many cardiovascular diseases natriuretic peptides serve not only as marker for diagnosis and prognosis but they have therapeutic importance. In the last years the potential use of the elevated BNP levels for diagnosis of pre-eclampsia was examined. In our review we discuss the current understanding of molecular biology, biochemistry and clinical relevance of natriuretic peptides.

Topics: Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Cardiovascular Diseases; Female; Humans; Liver Cirrhosis; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Natriuretic Peptides; Pre-Eclampsia; Pregnancy; Renal Insufficiency; Shock, Septic; Tissue Distribution

Cardiac natriuretic peptides consist of a family of six peptide hormones that are synthesised by three separate genes and then stored as three separate prohormones (i.e. 126 amino acid atrial natriuretic peptide (ANP), 108 amino acid B-type natriuretic peptide (BNP) and 103 amino acid C-type natriuretic peptide (CNP) prohormones). The ANP prohormone contains four peptide hormones: long-acting natriuretic peptide (LANP), vessel dilator, kaliuretic peptide and ANP. 2. Currently, the only natriuretic peptide available commercially to treat congestive heart failure (CHF) is BNP (Nesiritide/Natrecor; SCIOS, Sunnyvale, CA, USA), which causes a small increase in the urine volume of 90 38 mL/h compared with 67 27 mL/h and no significant natriuresis, but has beneficial haemodynamic effects in acute CHF individuals. These haemodynamic effects probably contribute to the side-effects of BNP in patients with acute CHF with a 27% incidence of hypotension and possibly to 22% worsening of renal function, defined as an increase in serum creatinine of 0.5 mg/dL, associated with a worse prognosis. A review of clinical trials suggests a twofold increased risk of death at 30 days post-nesiritide treatment, a finding that needs further investigation. 3. The best of the natriuretic peptides for treating chronic CHF is the vessel dilator, which increases urinary flow up to 13-fold and sodium excretion up to fourfold, without the previously mentioned side-effects. The natriuretic and diuretic effects of vessel dilators last 6 h, which would allow them to be used on a four times per day basis in treating chronic CHF. 4. Atrial natriuretic peptide does not cause significant improvement in acute renal failure (ARF) in humans. The only natriuretic peptide that significantly improves ARF is the vessel dilator. Even when ARF has been established for 2 days before treatment in an ischaemic ARF animal model, vessel dilator decreases serum creatinine from 8.2 0.5 to 0.98 0.12 mg/dL in 6 days. At day 6 of ARF, mortality decreases to 14% (from 88%) without the vessel dilator. After 6 days of treatment with the vessel dilator, the proximal and distal tubules regenerate. 5. In cancer, vessel dilator, LANP, kaliuretic peptide and ANP at 1 mmol/L, decrease up to 97% of human breast, pancreatic and prostate adenocarcinoma cells, as well as small cell and squamous cell lung cancer cells within 24 h. In vivo, vessel dilator, LANP and kaliuretic peptide completely stop the growth of human pancreati

Topics: Animals; Atrial Natriuretic Factor; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Neoplasms; Renal Insufficiency

The fact that the heart is able to secrete hormones, which are released in significant amounts in advance of certain cardiac conditions, has resulted in a wide range of opportunities and raised a multitude of questions. These hormones, named natriuretic peptides, possess diuretic, natriuretic and vasodilatory properties. The ones used in daily clinical practice are atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and their N-terminal fragments NT-proANP and NT-proBNP, respectively. Although most studies currently involve the use of BNP, the number involving NT-proBNP is expected to increase substantially in coming years because its level is less variable and its half-life longer. Nevertheless, at present there appears to be sufficient evidence to suggest that the plasma levels of these hormones will be extremely useful for the diagnosis, prognosis, screening, pharmacological monitoring, and treatment of patients with heart failure.

Topics: Atrial Natriuretic Factor; Biomarkers; Death, Sudden, Cardiac; Heart Failure; Hospitalization; Humans; Lung Diseases; Myocardium; Natriuretic Agents; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Natriuretic Peptides; Obesity; Prognosis; Renal Insufficiency; Ventricular Dysfunction, Left

Although recent major advances have developed a much better understanding of the pathophysiological pathways, tubulointerstitial fibrosis (TIF) is still currently incurable. Therefore, early detection may mean that the condition is more manageable than it was in the past. C-type natriuretic peptide (CNP) has been found to be a potent vasodilator but a weak natriuretic factor. In addition, CNP has also been believed to be produced in tubular cells and presented as a local modulator with anti-inflammatory and anti-proliferative effects. Elimination of CNP occurs by three main mechanisms, neutral endopeptidase, natriuretic peptide receptor-C and urinary excretion. Among them, the status of urinary CNP excretion in nephropathies is not yet fully elucidated. In the present study, subgroups of rats were subjected to unilateral ureteral obstruction (UUO) or sham operation and observed for 24h to 3 months. Urinary CNP excretion was significantly enhanced in UUO rats from 24h to 1 month post-ligation compared to sham-operated rats. Urinary CNP excretion was also markedly higher than CNP concentrations both in abdominal aorta and in renal vein, and almost identical concentrations in these two vessels excluded major renal extraction of circulating CNP of systemic origin. Urinary CNP excretion was negatively correlated with urinary protein concentration, blood urea nitrogen and creatinine, while positively correlated with albumin. In conclusion, the increased urinary CNP excretion is strongly associated with TIF progression, and may serve as an early marker of TIF.

Topics: Animals; Biomarkers; Blood Proteins; Blood Urea Nitrogen; Creatinine; Fibrosis; Kidney; Male; Natriuretic Peptide, C-Type; Organ Size; Rats; Rats, Wistar; Renal Insufficiency; Serum Albumin

Topics: Atrial Natriuretic Factor; Biomarkers; Heart Failure; Humans; Hypertension; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Renal Insufficiency

C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is considered to be involved in the regulation of vascular tone. Furthermore, the recent demonstration of CNP in human kidney and urine may indicate a role for CNP in fluid and electrolyte homeostasis. Therefore, the aim of the present study was to investigate the possible role of CNP in renal function disturbances in patients with cirrhosis of the liver.. Peripheral venous and urinary concentrations of CNP were determined in samples from 11 healthy controls, 20 cirrhotic patients with normal renal function (creatinine clearance 117 (8) ml/min), and 20 cirrhotic patients with impaired renal function (creatinine clearance 35 (4) ml/min). In a second protocol, arterial and renal venous plasma concentrations of CNP were determined in 37 patients with cirrhosis of the liver to estimate renal extraction ratios of CNP. A sensitive and specific radioimmunoassay was applied after solid phase extraction of samples.. Plasma CNP was lower in cirrhotic patients with normal and impaired renal function than in controls (3.0 (0.4) and 2.7 (0.2) v. 4.2 (0.4) pg/ml, respectively; p<0.05; mean (SEM)). In contrast, urinary CNP was higher in patients with impaired renal function compared with those with normal renal function and healthy controls (47.2 (7.4) v. 20.8 (1.9) and 17.0 (3.0) ng CNP/g creatinine, respectively; p<0.05). Urinary CNP was found to be inversely related to urinary sodium excretion in cirrhotic patients (r=-0.56; p<0.01). No differences were observed between arterial and renal venous concentrations of CNP in cirrhosis (2.4 (0.2) v. 2.4 (0.2) pg/ml). In cirrhotic patients with hepatorenal syndrome or refractory ascites (n=5), urinary CNP decreased from 132 (59) to 38 (7) ng/g creatinine (p<0.05) one week after either ornipressin infusion or insertion of a transjugular intrahepatic portosystemic shunt together with an increase in urinary sodium excretion from 27 (17) to 90 (34) mmol/24 hours.. Increased urinary CNP in cirrhotic patients in the absence of renal arteriovenous concentration gradients suggests enhanced renal CNP production in cirrhosis. Furthermore, an inverse relation between urinary CNP and urinary sodium excretion suggests a role for this peptide in renal sodium handling in patients with cirrhosis.

Topics: Analysis of Variance; Case-Control Studies; Child; Female; Humans; Kidney; Liver Cirrhosis; Male; Middle Aged; Natriuretic Peptide, C-Type; Renal Insufficiency; Sodium