Inhibition of the renin-angiotensin system in advanced chronic renal failure
Renin-angiotensin system (RAS) inhibitors, including angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), slow the progression of chronic kidney disease mild or moderate. However, results from some studies have suggested that stopping RAS inhibitors in patients with advanced chronic kidney disease may increase estimated glomerular filtration rate (eGFR) or slow its decline.
In this multicenter, open-label trial, we randomized patients with advanced and progressive chronic renal failure (eGFR, 2 body surface area) to discontinue or continue treatment with RAS inhibitors. The primary endpoint was eGFR at 3 years; eGFR values obtained after initiation of renal replacement therapy were excluded. Secondary outcomes included development of end-stage renal disease (ESKD); a composite of greater than 50% decrease in eGFR or initiation of renal replacement therapy, including ESKD; hospitalization; arterial pressure; exercise capacity; and quality of life. Predefined subgroups were defined according to age, eGFR, type of diabetes, mean arterial pressure and proteinuria.
At 3 years, among the 411 patients included, the mean least squares (±SE) eGFR was 12.6±0.7 ml per minute for 1.73 m2 in the stop group and 13.3 ± 0.6 ml per minute per 1.73 m2 in the continuation group (difference, -0.7; 95% confidence interval [CI], -2.5 to 1.0; P = 0.42), with a negative value favoring the outcome in the continuation group. No heterogeneity in the results according to the predefined subgroups was observed. ESKD or initiation of renal replacement therapy occurred in 128 patients (62%) in the discontinuation group and 115 patients (56%) in the continuation group (relative risk, 1.28; 95% CI, 0.99 to 1.65). Adverse events were similar in the discontinuation and continuation groups with respect to cardiovascular events (108 versus 88) and deaths (20 versus 22).
In patients with advanced and progressive chronic renal failure, discontinuation of RAS inhibitors was not associated with a significant difference between groups in the rate of long-term decrease in eGFR. (Funded by the National Institute for Health Research and the Medical Research Council; STOP ACEi EudraCT number, 2013-003798-82; ISTRCTN number, 62869767.)