Efficacy and Safety of Benazepril for Advanced Chronic Renal Insufficiency

Treatment with ACE inhibitors slows the progression of proteinuric kidney disease, but physicians are often worried about using these medications in patients with reduced kidney function -- the group of patients who might benefit the most -- because of the potential risks of hyperkalemia and acute renal failure.

Once, after starting a patient with a creatinine of 3 on an ACE inhibitor, I was asked for evidence that the benefits of ACE inhibitors in these patients outweigh the risks. It's a reasonable question that was only recently answered. An article in this month's NEJM, Efficacy and Safety of Benazepril for Advanced Chronic Renal Insufficiency, provides evidence that ACE inhibitors should be used in patients with proteinuric renal disease, even if the creatinine is 3 - 5. However, while this study showed a substantial benefit in slowing the decline of renal function, the danger for misuse of ACE inhibitors without sufficient monitoring exists. This might lead to an increase in hyperkalemia and other side effects, similar to the increase in serious hyperkalemia related to spironolactone after the RALES study was published.

From The New England Journal of Medicine:

Background Angiotensin-converting–enzyme inhibitors provide renal protection in patients with mild-to-moderate renal insufficiency (serum creatinine level, 3.0 mg per deciliter or less). We assessed the efficacy and safety of benazepril in patients without diabetes who had advanced renal insufficiency.

Methods We enrolled 422 patients in a randomized, double-blind study. After an eight-week run-in period, 104 patients with serum creatinine levels of 1.5 to 3.0 mg per deciliter (group 1) received 20 mg of benazepril per day, whereas 224 patients with serum creatinine levels of 3.1 to 5.0 mg per deciliter (group 2) were randomly assigned to receive 20 mg of benazepril per day (112 patients) or placebo (112 patients) and then followed for a mean of 3.4 years. All patients received conventional antihypertensive therapy. The primary outcome was the composite of a doubling of the serum creatinine level, end-stage renal disease, or death. Secondary end points included changes in the level of proteinuria and the rate of progression of renal disease.

Results Of 102 patients in group 1, 22 (22 percent) reached the primary end point, as compared with 44 of 108 patients given benazepril in group 2 (41 percent) and 65 of 107 patients given placebo in group 2 (60 percent). As compared with placebo, benazepril was associated with a 43 percent reduction in the risk of the primary end point in group 2 (P=0.005). This benefit did not appear to be attributable to blood-pressure control. Benazepril therapy was associated with a 52 percent reduction in the level of proteinuria and a reduction of 23 percent in the rate of decline in renal function. The overall incidence of major adverse events in the benazepril and placebo subgroups of group 2 was similar.

Conclusions Benazepril conferred substantial renal benefits in patients without diabetes who had advanced renal insufficiency.

Technorati Tags: Benazepril, Kidney Disease, Chronic Kidney Disease, New England Journal of Medicine