Nesiritide Does Not Improve Renal Function in Patients With Chronic Heart Failure and Worsening Serum Creatinine

Abstract

Background-Nesiritide (synthetic human brain natriuretic peptide) is approved for the treatment of symptomatic heart failure. However, studies of brain natriuretic peptide in patients with heart failure have come to conflicting conclusions about effects on glomerular filtration rate (GFR), effective renal plasma flow, natriuresis, and diuresis. Methods and Results-To identify a population at high risk of renal dysfunction with conventional treatment, we selected patients with a creatinine level increased from baseline (within 6 months). We examined the effects of nesiritide on GFR (measured by iothalamate clearance), renal plasma flow (measured by para-amino hippurate clearance), urinary sodium excretion, and urine output in a double-blind, placebo-controlled, crossover study. Patients received nesiritide (2 g/kg IV bolus followed by an infusion of 0.01 g/kg per minute) or placebo for 24 hours on consecutive days. Nesiritide and placebo data were compared by repeated-measures analysis and Student t test. We studied 15 patients with a recent mean baseline creatinine of 1.5Ϯ0.4 mg/dL and serum creatinine of 1.8Ϯ0.8 mg/dL on admission to the study. There were no differences in GFR, effective renal plasma flow, urine output, or sodium excretion for any time interval or for the entire 24-hour period between the nesiritide and placebo study days. For 24 hours, urine output was 113Ϯ51 mL/h with placebo and 110Ϯ56 mL/h with nesiritide. GFR during placebo was 40.9Ϯ25.9 mL/min and with nesiritide was 40.9Ϯ25.8. Conclusions-Nesiritide did not improve renal function in patients with decompensated heart failure, mild chronic renal insufficiency, and renal function that had worsened compared with baseline. The lack of effect may be related to renal insufficiency, hemodynamic alterations, sodium balance, severity of heart failure, or drug dose. Understanding the importance of these issues will permit effective and appropriate use of nesiritide.

Multicenter Prospective Investigation on Efficacy and Safety of Carperitide as a First-Line Drug for Acute Heart Failure Syndrome With Preserved Blood Pressure COMPASS: Carperitide Effects Observed Through Monitoring Dyspnea in Acute Decompensated Heart Failure Study

“…Third, the effects of carperitide on renal function, which is of concern when using nesiritide (hBNP), were not assessed in the present study because renal function parameters were not measured over time after the start of treatment. 19,20 Further studies of carperitide as a first-line drug are warranted to investigate its effects on renal function.…”

Maximizing the Renal Cyclic 3′-5′-Guanosine Monophosphate System with Type V Phosphodiesterase Inhibition and Exogenous Natriuretic Peptide

“…With regard to the kidney, we previously reported, as have others, that the glomerular, natriuretic, and urinary cGMP excretory responses to both atrial natriuretic peptide and brain NP (BNP) are attenuated in overt experimental and human CHF (6,7). In addition, Nesiritide, the recombinant human BNP (Scios, Inc., Fremont, CA) that is approved for the management of acute decompensated CHF, in some clinical studies failed to demonstrate a renal-enhancing property (8,9). The exact mechanisms that mediate the attenuated response to NP in overt CHF remain poorly defined and most likely are multifactorial.…”

The Mechanism of Action of LCZ696

“…While nesiritide has been shown to produce a modest improvement in dyspnoea, it does not favourably affect clinical outcomes, decongestion or renal function [33][34][35] and safety concerns have been raised. 36,37 Blockade of NP breakdown by neprilysin inhibitors has, therefore, been investigated.…”