Nesiritide does not improve renal function in patients with chronic heart failure and worsening serum creatinine.
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.


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 microg/kg IV bolus followed by an infusion of 0.01 microg/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 1.5+/-0.4 mg/dL and serum creatinine of 1.8+/-0.8 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 113+/-51 mL/h with placebo and 110+/-56 mL/h with nesiritide. GFR during placebo was 40.9+/-25.9 mL/min and with nesiritide was 40.9+/-25.8.


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.
Wang
David J
DJ
Department of Medicine, University of Maryland School of Medicine, and Baltimore Veterans Administration Medical Center, USA.
Dowling
Thomas C
TC
Meadows
Dean
D
Ayala
Tomas
T
Marshall
Joanne
J
Minshall
Stacey
S
Greenberg
Nancy
N
Thattassery
Emil
E
Fisher
Michael L
ML
Rao
Krishnamurti
K
Gottlieb
Stephen S
SS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002908:Chronic Disease; D003404:Creatinine / Q000097:blood; D018592:Cross-Over Studies; D004231:Diuresis / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D007674:Kidney Diseases / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects; D045283:Natriuretic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D020097:Natriuretic Peptide, Brain / Q000494:pharmacology / Q000627:therapeutic use*; D012079:Renal Circulation / Q000187:drug effects; D017211:Treatment Failure; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use
D045283:Natriuretic Agents; D014665:Vasodilator Agents; D020097:Natriuretic Peptide, Brain; D003404:Creatinine