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Over the last 3 decades, there has been a remarkable explosion in our understanding of the natriuretic peptide system. Among articles published before 1980, only 1 entry can be found in Medline under the search term natriuretic peptide. Currently, however, there are >22 500 publications. In this impressive collection of literature, the concept of the natriuretic peptide as an ideal cardiorenal therapeutic emerged with reports of improvement in renal function, neurohormonal activation, fibrosis, and natriuresis among other benefits with these agents.1 As a result, the development of recombinant B-type natriuretic peptide (nesiritide) brought tremendous optimism in terms of its potential role in acute decompensated heart failure (ADHF). The drug was approved in 2001 on the basis of a 489-patient trial that did not actually evaluate its cardiorenal effects but rather demonstrated efficacy via its actions as a vasodilator.2 This took the form of a 2-mm Hg-greater reduction in pulmonary capillary wedge pressure with no additional relief of dyspnea compared with nitroglycerin but significant superiority over placebo. However, presumably as a result of the great enthusiasm for the mechanism of the drug, sales soared to $390 million by 2004 despite the absence of any large studies showing positive clinical outcomes and even some human data indicating an absence of positive cardiorenal effects.3,4 The widespread enthusiasm for nesiritide ended rather abruptly in 2005 after publication of 2 meta-analyses by Sackner-Bernstein et al5,6 demonstrating a 52% increased risk for worsening renal function (WRF; defined as a >0.5-mg/dL increase in creatinine) and an 80% increased risk for death with nesiritide.Article see p 958The above chain of events motivated the Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF) trial, which was designed to definitively answer the question of safety and efficacy of nesiritide …

Renal Subanalysis of the Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF)