BNP as a Major Player in the Heart-Kidney Connection

Hospital chronicles, 2015

Brain natriuretic peptide (BNP) is a peptide hormone secreted by cardiomyocytes in response to atrial or ventricular wall stretch. It promotes a number of systemic effects, including vasodilatation, increase in urinary output and sodium excretion as well as inhibition of the sympathetic nervous system and the renin–angiotensin–aldosterone system. Plasma BNP levels have been reported to be elevated in patients with left ventricular hypertrophy, congestive heart failure, acute coronary syndromes, atrial fibrillation and impaired renal function. Moreover, elevated BNP levels have been shown to be a strong predictor of morbidity and mortality in patients with heart failure. Interestingly, it has also been found that the N-terminal peptide of BNP is slightly superior to BNP for predicting death or re-hospitalization for heart failure. Presumably, it is the longer half-life of NT-pro-BNP that may promote it as a more accurate index of ventricular stress and therefore a better predictor of...

Background Brain natriuretic peptide (BNP) is an important biomarker for patients with cardiovascular diseases, including heart failure, hypertension and cardiac hypertrophy. It is also known that BNP levels are relatively higher in patients with chronic kidney disease and no heart disease; however, the mechanism remains unclear.

Mayo Clinic Proceedings, 2001

Objectives: To determine levels of natriuretic peptides (NPs) in patients with end-stage renal disease (ESRD) and to examine the relationship of these cardiovascular peptides to left ventricular hypertrophy (LVH) and to cardiac mortality. • Patients and Methods: One hundred twelve dialysis patients without clinical evidence of congestive heart failure underwent plasma measurement of NP concentrations and echocardiographic investigation for left ventricular mass index (LVMI). • Results: Plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations correlated positively with LVMI and inversely with left ventricular ejection fraction, whereas C-type NP and Dendroaspis NP levels did not correlate with LVMI. In dialysis patients with LVH (LVMI >125 g/m 2 ), plasma ANP and BNP concentrations were increased compared with those in dialysis patients without LVH (both P<.001). In a subset of 15 dialysis patients without LVH or other concomitant diseases, plasma BNP concentrations were not significantly increased compared with those in 35 controls (mean ± SD, 20.1±13.4 vs 13.5±9.6 pg/mL; P=.06), demonstrating that the BNP concentration was not increased by renal dysfunction alone. Furthermore, the BNP level was signifi-ANP = atrial natriuretic peptide; AUC = area under the curve; BNP = brain natriuretic peptide; CAD = coronary artery disease; CHF = congestive heart failure; CNP = C-type natriuretic peptide; DNP = Dendroaspis natriuretic peptide; DNP-LI = DNP-like immunoreactivity; ESRD = end-stage renal disease; IVST = intraventricular septum thickness; Kt/V = fractional urea clearance rate; LVD = left ventricular systolic dysfunction; LVEF = left ventricular ejection fraction; LVH = left ventricular hypertrophy; LVMI = left ventricular mass index; MI = myocardial infarction; NP = natriuretic peptide; PWT = posterior wall thickness; ROC = receiver operating characteristic cantly higher in the 16 patients who died from cardiovascular causes compared with survivors (mean ± SD, 129±13 vs 57±7 pg/mL; P<.003) and was significantly associated with greater risk of cardiovascular death in Cox regression analysis (P<.001), as was the ANP level (P=.002). • Conclusions: Elevation of the plasma BNP concentration is more specifically related to LVH compared with the other NP levels in patients with ESRD independent of congestive heart failure. Thus, BNP serves as an important plasma biomarker for ventricular hypertrophy in dialysis patients with ESRD. Mayo Clin Proc. 2001;76:1111-1119

Journal of Cellular and Molecular Medicine, 2007

• Introduction• Natriuretic peptides as a ‘biomarker’ of congestive heart failure and acute renal failure/insufficiency• Renoprotective effect of natriuretic peptides after acute renal failure• Nesiritide – current benefits/hazards of drug usage• Introduction• Natriuretic peptides as a ‘biomarker’ of congestive heart failure and acute renal failure/insufficiency• Renoprotective effect of natriuretic peptides after acute renal failure• Nesiritide – current benefits/hazards of drug usageIntroductionNatriuretic peptides as a ‘biomarker’ of congestive heart failure and acute renal failure/insufficiencyRenoprotective effect of natriuretic peptides after acute renal failureNesiritide – current benefits/hazards of drug usageAbstractThe natriuretic peptides are a family of related hormones that play a crucial role in cardiovascular and renal homeostasis. They have recently emerged as potentially important clinical biomarkers in heart failure. Natriuretic peptides, particularly brain natriuretic peptide (BNP) and the inactive N-terminal fragment of BNP, NT-proBNP, that has an even greater half-life than BNP, are elevated in heart failure and therefore considered to be excellent predictors of disease outcome. Nesiritide, a recombinant human BNP, has been shown to provide symptomatic and haemodynamic improvement in acute decompensated heart failure, although recent reports have suggested an increased short-term risk of death with nesiritide use. This review article describes: the current use of BNP and its inactive precursor NT-proBNP in diagnosis, screening, prognosis and monitoring of therapy for congestive heart failure, the renoprotective actions of natriuretic peptides after renal failure and the controversy around the therapeutic use of the recombinant human BNP nesiritide.The natriuretic peptides are a family of related hormones that play a crucial role in cardiovascular and renal homeostasis. They have recently emerged as potentially important clinical biomarkers in heart failure. Natriuretic peptides, particularly brain natriuretic peptide (BNP) and the inactive N-terminal fragment of BNP, NT-proBNP, that has an even greater half-life than BNP, are elevated in heart failure and therefore considered to be excellent predictors of disease outcome. Nesiritide, a recombinant human BNP, has been shown to provide symptomatic and haemodynamic improvement in acute decompensated heart failure, although recent reports have suggested an increased short-term risk of death with nesiritide use. This review article describes: the current use of BNP and its inactive precursor NT-proBNP in diagnosis, screening, prognosis and monitoring of therapy for congestive heart failure, the renoprotective actions of natriuretic peptides after renal failure and the controversy around the therapeutic use of the recombinant human BNP nesiritide.

2010

BACKGROUND The interactions between pressure and volume overload that occur in hypertension lead to different patterns of cardiac hypertrophy and to increase in natriuretic peptides (NPs). The profiles of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) synthesis and secretion have been investigated in models of hypertension. However, the different evolution of these profiles during the acute and chronic periods of pressure overload-induced cardiac hypertrophy is still unknown. For this reason, we studied one-kidney, one clip model using Sprague-Dawley rats at weeks 2, 4, 6 and 12 and correlated the evolution of these profiles with cardiac hypertrophy and hypertension. We observed a positive correlation between blood pressure elevation and the degree of cardiac hypertrophy, with a time-dependent increase in both parameters from week 2. Levels of BNP expression showed an early increase after 2 weeks of treatment while ANP increased significantly after 6 weeks. Yet...

The Journal of Heart and Lung Transplantation, 2006

Clinical Science, 2005

In the present study, we investigated the potential of N-BNP (N-terminal B-type natriuretic peptide) as a prognostic marker for risk of CV (cardiovascular) events, overall mortality and progression to ESRD (end-stage renal disease) in a cohort of 83 pre-dialysis CKD (chronic kidney disease) patients without clinical evidence of heart failure. During the study, ten patients reached the combined end point of overall mortality and/or CV event. Univariate factors associated with the combined end point were plasma N-BNP (P&lt;0.0005), creatinine (P&lt;0.002), systolic blood pressure (P&lt;0.009) and age (P&lt;0.015). N-BNP levels were higher in patients with CV events (P&lt;0.0005). Cox model regression analysis yielded log10 N-BNP (hazard ratio, 9.608; P&lt;0.007) and pre-existing CV disease (hazard ratio, 4.571; P&lt;0.029) as independent predictors of overall mortality or CV events. Kaplan–Meier analysis curves for the subgroup with supramedian creatinine levels (225 μmol/l) showed si...

Cardiovascular Research, 2006

Atrial natriuretic peptide (ANP) and brain (B-type) natriuretic peptide (BNP) are circulating hormones of cardiac origin that play an important role in the regulation of intravascular blood volume and vascular tone. The plasma concentrations of ANP and BNP are elevated in heart failure, and they are considered to compensate for heart failure because of their diuretic, natriuretic, and vasodilating actions and inhibitory effects on renin and aldosterone secretion. Evidence is also accumulating from recent work that ANP and BNP exert their cardioprotective functions not only as circulating hormones but also as local autocrine and/or paracrine factors. In studies using cultured neonatal myocytes and fibroblasts, exogenous administration of both ANP and ANP antagonists demonstrated that ANP has antihypertrophic and antifibrotic functions. Corroborating these in vitro results, mice lacking natriuretic receptor-A (NPR-A), the receptor for ANP and BNP, develop cardiac hypertrophy and fibrosis independent of their blood pressure. Recent studies also suggest that the intracardiac natriuretic peptides/cGMP system plays a counter-regulatory role against the intracardiac renin -angiotensin -aldosterone system and TGF-beta mediated pathway. In a clinical setting, human recombinant ANP and BNP may be used for a therapy of heart failure; however, further evaluation is required in the future.

2004

Natriuretic peptides have emerged as important candidates for development of diagnostic tools and therapeutic agents in cardiovascular disease. The family contains of three major peptides-ANP, BNP, CNP-that participate in cardiovascular and cardiorenal homeostasis. Each of these natriuretic peptides binds differentially to specific receptors that signal through different mechanisms. They are cleared enzymatically by neutral endopeptidase as well as by receptor-mediated endocytosis. Because of its fast induction and specific expression in overt heart failure, BNP seems the most promising natriuretic peptide. It is predominantly synthesized in the cardiac ventricles, released as pre-proBNP and then enzymatically cleaved to BNP and the Nterminal portion of BNP(NT-proBNP). Blood measurements of BNP and NT-proBNP have been shown to identify patients with LV dysfunction. This review focuses on the physiology of natriuretic peptides as a group and brain natriuretic peptide in more detail, its structure and regulation as well as its effects at the cellular level.