ACE inhibitor benefits advanced kidney disease

13 January 2006

Including the ACE inhibitor benazepril in antihypertensive treatment offers multiple benefits to patients with advanced chronic kidney disease, trial findings indicate.

Treatment with benazepril both stalled the progression of renal disease and improved survival compared with placebo in patients receiving drug treatment for hypertension, say the investigators.

"Benazepril therapy was associated with a significant improvement in renal outcome and surpassed that attributable to blood-pressure control in patients without diabetes who had advanced renal dysfunction," they report in the New England Journal of Medicine.

ACE inhibitors have been found to provide renal protection in patients with mild-to-moderate renal insufficiency (serum creatinine ≤3.0 mg/dl), says the team, but many physicians are reluctant to use them in patients with advanced renal insufficiency due to unease that serum creatinine or potassium levels will rise.

To test whether these concerns are justified, researchers from Nanfang Hospital in Guangzhou, China, randomly assigned 104 patients with serum creatinine levels of 1.5-3.0 mg/dl (group 1) to receive 20 mg benazepril per day, and 224 with serum creatinine levels of 3.1-5.0 mg/dl (group 2) to receive 20 mg benazepril per day or placebo, after an 8-week run-in period.

All patients also received conventional antihypertensive treatment.

During the next 3.4 years, 41% of group 2 patients receiving benazepril reached the primary composite endpoint of a doubling of serum creatinine level, end-stage renal disease or death and 60% of those receiving placebo – a 43% reduction with the ACE inhibitor (p=0.005). Primary endpoint events occurred in 22% of group 1.

Benazepril therapy was also associated with a 52% reduction in the level of proteinuria, and a 23% reduction in the rate of decline of renal function (p=0.02 in both cases).

"Our findings indicate that benazepril, along with conventional antihypertensive treatment, as needed, confers renal protection in patients without diabetes who have advanced renal insufficiency," Fan Fan Hou and fellow researchers conclude.

"Since current information indicates that 85% of patients with stage 4 chronic kidney disease are not offered such renal protective treatment [with ACE inhibitors] our results may have important implications for the development of new therapeutic guidelines."

In an editorial accompanying the study, Lee Hebert (Ohio State University Medical Center, Columbus) says the results suggest that it is worthwhile continuing ACE inhibitors in patients with chronic kidney disease even if serum creatinine level continues to climb.

He adds: "By demonstrating that ACE inhibitors can be used successfully in patients with advanced chronic kidney disease, Hou et al suggest that abandoning treatment with an ACE inhibitor (or angiotensin-receptor blocker) when chronic kidney disease progresses to stage 3 or 4 is not necessary and hastens the onset of end-stage renal disease."

N Engl J Med 2006; 354: 131-140