Renal Function and Heart Failure Treatment
When Is a Loss Really a Gain?
A number of studies have demonstrated a linkage between renal dysfunction and adverse clinical outcomes in both acute and chronic heart failure.1–3 Heart failure treatments can affect renal function in a variety of ways, with decreased glomerular filtration rate (GFR) during treatment often denoting a poorer prognosis.4–6 Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) reduce GFR through intrarenal mechanisms yet convey reduced rates of morbidity and mortality, presenting the hypothesis that the association between change in GFR and clinical outcomes depends on the factors that drive that change more than on GFR itself. In this issue of Circulation: Heart Failure, Testani et al7 present evidence that supports this hypothesis, showing that within the SOLVD (Studies of Left Ventricular Dysfunction) study, early reduction in GFR was associated with increased mortality within the placebo group but not in the enalapril group. It is reasonable to conclude that inhibiting the renin-angiotensin system (RAS) reduces GFR through a mechanism that does not convey an adverse prognosis. In evaluating new therapies, focus should be placed on clarifying the pathways through which agents influence renal function.
Article see p 685
Within the SOLVD study, despite exclusion of patients with serum creatinine of >2.0 mg/dL, baseline renal impairment was associated with reduced survival.2,3 Patients randomized to enalapril showed slight, but statistically significant mean increases in serum creatinine during treatment relative to those receiving placebo.8,9 There exist a number of putative mechanisms whereby heart failure therapies may influence renal function. Diuretics may predispose to prerenal azotemia through intravascular volume depletion, excessive cardiac preload reduction, and a resulting reduction in cardiac output. Loop diuretics also induce intrarenal mechanisms for reducing GFR, principally through adenosine release and diminished glomerular blood flow …