Discontinuing renin-angiotensin system (RAS) inhibitors in patients with advanced or progressing chronic kidney disease (CKD) does not result in a clinically relevant change in estimated glomerular filtration rate (eGFR) or difference in the rate of long-term decline in eGFR, according to study findings presented at the American Society of Nephrology’s Kidney Week 2022 conference in Orlando, Florida, and published concomitantly in The New England Journal of Medicine.

A previous small observational study suggested that discontinuation of ACE inhibitors or angiotensin receptor blockers in patients with advanced CKD may increase eGFR. In addition, current guidelines do not specifically address the use of RAS inhibitors in advanced CKD.

Sunil Bhandari, PhD, of Hull University Teaching Hospitals NHS Trust in Kingston upon Hull, UK, and colleagues conducted the multicenter, open-label STOP-ACEi trial to determine whether discontinuation of these agents could slow progression of CKD in patients with stage 4-5 CKD. They randomly assigned patients to either discontinue or to continue RAS inhibitors. The eGFR at 3 years was the primary study outcome. The study enrolled 411 patients.

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At 3 years, the least-squares mean eGFR was 12.6 mL/min/1.73 m2 in the discontinuation group and 13.3 mL/min/1.73 m2 in the continuation group, Dr Bhandari’s team reported in a poster presentation. End-stage kidney disease or initiation of renal replacement therapy occurred in 128 patients (62%) in the discontinuation group and 115 patients (56%) in the continuation group. None of these between-group differences were statistically significant. The study arms had a similar incidence of adverse cardiovascular events and deaths.

“If indicated for the treatment of hypertension, proteinuria or cardiovascular disease, [RAS inhibitors] should not be stopped just because eGFR is low,” Dr Bhandari and colleagues concluded.


Bhandari S, Khwaja A, Ives N, et al. Multi-center randomized controlled trial of angiotensin converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB) withdrawal in advanced kidney disease: The STOP-ACEi trial. Presented at: Kidney Week 2022; November 3-6, Orlando, Florida. Abstract TH-PO966.

Bhandari S, Mehta S, Khwaja A, et al. Renin-angiotensin system inhibition in advanced chronic kidney disease. N Engl J Med. Published online ahead of print November 3, 2022. doi:10.1056/NEJMoa2210639