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ACE Inhibitor Is Beneficial in Advanced Renal Insufficiency

In a randomized trial, benazepril delayed progression of advanced renal insufficiency in nondiabetic patients; the effect was apparently not mediated by better control of hypertension.

Many clinicians avoid angiotensin-converting–enzyme (ACE) inhibitors in patients with advanced renal insufficiency because of concern about hyperkalemia and further deterioration in renal function. In this randomized double-blind trial from China, researchers examined the effect of the ACE inhibitor benazepril in nondiabetic patients with serum creatinine levels of 3.1 to 5.0 mg/dL and proteinuria (>300 mg/day). The underlying diagnosis was glomerular disease in 62% of patients.

Initially, 281 patients were identified. During an 8-week run-in phase, in which renal function was monitored closely while all patients received benazepril, 57 patients were excluded, most commonly because of dry cough (42), a greater than 30% increase in serum creatinine (6), or hyperkalemia (4). The remaining 224 patients received either benazepril (10 mg twice daily) or placebo; other antihypertensive drugs (except for angiotensin-receptor blockers) were permitted. The primary composite endpoint was doubling of serum creatinine, need for dialysis or transplantation, or death. During an average follow-up of about 3 years, this endpoint was reached by a significantly smaller proportion of the benazepril group than the placebo group (41% vs. 60%). The mean level of proteinuria decreased by 52% with benazepril and 20% with placebo — also a significant difference. However, no difference was noted between groups in blood pressure control. Adverse events were similar in the two groups.

Comment: In nondiabetic patients, the ACE inhibitor benazepril delayed progression of advanced renal insufficiency. This effect was apparently not mediated by better control of hypertension. Because of the potential risks associated with ACE inhibition, an editorialist provides guidance on how to introduce these drugs safely in this patient population.

— Allan S. Brett, MD

Published in Journal Watch General Medicine January 17, 2006

Citation(s):

Hou FF et al. Efficacy and safety of benazepril for advanced chronic renal insufficiency. N Engl J Med 2006 Jan 12; 354:131-40.

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• Medline abstract (Free)

Hebert LA. Optimizing ACE-inhibitor therapy for chronic kidney disease. N Engl J Med 2006 Jan 12; 354:189-91.

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• Medline abstract (Free)