Benazepril is renoprotective in patients with severe chronic kidney disease

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Abstract

BACKGROUND

It is not known whether the beneficial effect of angiotensin-converting-enzyme inhibitors (ACEIs) in chronic kidney disease (CKD) encompasses advanced stages of this condition.

OBJECTIVE

To establish whether benazepril is renoprotective in advanced CKD.

DESIGN

Adults aged ≤70 years with CKD not due to diabetes were recruited for this randomized, double-blind, single-center Chinese study. Screening took place from May 1999 to May 2001; patients with serum creatinine levels of 1.5-5.0 mg/dl (133-442 μmol/l), stable creatinine clearances of 20-70 ml/min/1.73 m2 and persistent proteinuria were eligible to enroll if they had been free of ACEIs and angiotensin-receptor blockers for 6 weeks. Patients requiring dialysis were excluded.

INTERVENTION

The study protocol included an 8-week run-in, beginning with 4 weeks on benazepril 10 mg once daily, which was increased to twice daily for the second 4 weeks if no major increases in serum creatinine (≥30%) or potassium (to ≥5.6 mmol/l) occurred. The next 3 weeks were spent off benazepril. Patients with serum creatinine levels of 1.5-3.0 mg/dl (133-265 μmol/l) then restarted benazepril 10 mg twice daily, and those with serum creatinine levels of 3.1-5.0 mg/dl (274-442 μmol/l) were randomized to benazepril 10 mg twice daily or placebo. Throughout the trial, additional non-renin-angiotensin-system-blocking antihypertensives were used to maintain a blood pressure of <130/80 mmHg. Patients were followed for 3 years.

OUTCOME MEASURE

The primary endpoint was a combination of a twofold increase in serum creatinine from baseline, end-stage renal disease and death.

RESULTS

Similar proportions of patients were excluded from the two creatinine-stratified groups during run-in. Data from 317 participants (mean follow-up 3.4 years) were eligible for the intention-to-treat analysis. Demographics and rate of blood pressure decline were similar in the three treatment groups. The proportion of patients with serum creatinine levels of 3.1-5.0 mg/dl who experienced an endpoint was significantly lower among those on benazepril (44/107) than among those on placebo (65/108; 41% vs 60%; P = 0.004), but remained higher than among patients with serum creatinine levels of 1.5-3.0 mg/dl (22/102 [22%]; P = 0.003). For patients with serum creatinine levels of 3.1-5.0 mg/dl, benazepril conferred a significant reduction in the likelihood of experiencing an endpoint (43%; P = 0.005), even when variation in mean arterial pressure was taken into account (P = 0.009). Urine protein excretion in the patients with serum creatinine levels of 3.1-5.0 mg/dl was reduced significantly more with benazepril than with placebo (52% vs 20%; P <0.001). The rate of deterioration in renal function (reciprocal of the serum creatinine concentration) in the patients with serum creatinine levels of 3.1-5.0 mg/dl was 23% lower with benazepril than with placebo (P = 0.02). The frequency of major adverse events in the patients with serum creatinine levels of 3.1-5.0 mg/dl did not differ significantly between the benazepril and placebo subgroups.

CONCLUSION

For patients with severe chronic renal insufficiency, benazepril has beneficial renal effects and acceptable safety.

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