Inhibition of the renin-angiotensin system in advanced chronic kidney disease
Inhibitors of the renin-angiotensin system (RAS) — including angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) — slow the progression of mild to moderate chronic kidney disease. However, the results of some studies suggest that stopping RAS inhibitors in patients with advanced chronic kidney disease may increase the estimated glomerular filtration rate (eGFR) or slow its decline.
In this multicenter, open-label trial, we randomized patients with advanced and progressive CKD (eGFR, <30 mL/min at 1.73 m2 body surface) or discontinue or continue RAS inhibitor therapy. The primary outcome was eGFR at 3 years; eGFR values obtained after starting renal replacement therapy were excluded. Secondary outcomes included the development of end-stage renal disease (ESRD); combination of eGFR reduction of more than 50% or initiation of renal replacement therapy, including ESKD; hospitalization; blood pressure; exercise capacity; and quality of life. Prespecified subgroups were defined according to age, eGFR, type of diabetes, mean arterial pressure, and proteinuria.
After 3 years, among the 411 patients enrolled, the mean squared (±SE) eGFR was 12.6±0.7 ml per minute at 1.73 m2 in the treatment discontinuation group and 13.3±0.6 ml per minute at 1.73 m2 in teaching 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 outcome was observed according to prespecified subgroups. ESKD or initiation of renal replacement therapy occurred in 128 patients (62%) in the discontinuation group and in 115 patients (56%) in the continuation group (hazard ratio, 1.28; 95% CI, 0.99 to 1, 65). Adverse events were similar in the discontinuation group and the continuation group in terms of cardiovascular events (108 vs 88) and death (20 vs 22).
Among patients with advanced and progressive chronic kidney disease, discontinuation of RAS inhibitor therapy was not associated with a significant difference between groups in the long-term rate of eGFR decline. (Funded by the National Institute for Health Research and the Medical Research Council; STOP ACEi EudraCT number, 2013-003798-82; ISTRCTN number, 62869767.)
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