Effect of Intermittent Nesiritide Administration on Kidney Function

Abstract

We read with interest the recent article by Ng et al that described no difference in the incidence of acute renal injury in patients with acute decompensated heart failure (HF) receiving either nitroglycerin or nesiritide. On the other hand, their results suggested preservation of renal function by nesiritide. This prompted us to report our findings on the effect of periodic outpatient administration of nesiritide on renal function in patients with refractory HF unresponsive to optimal oral therapy. We reviewed the charts of 46 patients with chronic HF refractory to optimal oral therapy who received intermittent nesiritide infusions at the HF clinic at Huntsville Hospital, Alabama, United States. Intravenous nesiritide was given as a bolus of 2 mcg/kg followed by 0.01 mcg/kg per min over 4 to 6 hours at each visit to the clinic (ranged from twice a week to once every 3 weeks depending on the severity of symptoms). Patients were followed over a period of 6 months for worsening of renal function defined as an increase in serum creatinine of more than 0.5 mg/dL. We excluded patients with baseline serum creatinine of >2.5 mg/dL or those on dialysis. Patients received between 8 and 40 infusions of nesiritide during the 6-month period, none of them received an inotropic agent because of clinical evidence of decompensated HF and none died during the study period. At the beginning of the study, mean serum creatinine was 1.28 + 0.48 mg/dL, with no significant change after 6 months, 1.29 + 0.50 mg/dL (P > .05). None of the patients had an increase in serum creatinine of more than 0.5 mg/dL at the end of the study. Our findings suggest that repetitive administration of nesiritide does not worsen kidney function as assessed by serum creatinine and are in agreement with the findings of Ng et al. When assessing the kidney function based on the definition of Ng et al, an acute rise in creatinine of 0.3 mg/dL or 25% from the baseline, we noted that only 2 of 45 patients met this definition (P > .05). This study was limited by its open-label design, the relatively small number of patients studied, and the absence of a comparable group. The concern about nesiritide’s negative effect on renal function stemmed from a meta-analysis that suggested an increased risk of worsening renal function associated with the use of nesiritide. Although the meta-analysis is certainly hypothesis generating, part of the data used in this analysis were pooled from early dosing trials where the doses of nesiritide used were higher than the US Food and Drug Administration (FDA)approved dose. In addition, none of them were powered to look at the effect of nesiritide on renal function. On the other hand, the recent landmark Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF) trial, a randomized trial with >7000 patients, has concluded that nesiritide does not compromise renal function when used in acute decompensated HF. In addition, other recent studies suggest that there was no evidence of worsening renal function with nesiritide. Our study differs from those trials as our patients did not have decompensated HF, yet they had severe symptoms despite optimal oral therapy. In addition, our patients received multiple nesiritide infusions, ranging from 8 to 40, over a 6-month period. Despite receiving repetitive dosing of intravenous nesiritide, patients with chronic HF refractory to optimal oral therapy maintained a stable renal function over a 6-month period. Nesiritide seems to be safe and does not compromise renal function. Yet, the drug should not be used for intermittent outpatient infusions and should be limited to inpatients use, as approved by FDA.