Renin–Angiotensin System Inhibition in Advanced Chronic Kidney Disease

This multicenter, open-label randomized controlled trial (STOP ACEi) investigated whether discontinuing renin–angiotensin system (RAS) inhibitors—ACE inhibitors and ARBs—in patients with advanced, progressive chronic kidney disease (CKD) would alter long-term kidney outcomes. A total of 411 adults (eGFR < 30 ml/min/1.73 m² with ≥2 ml/year decline over 2 years) were randomized to either continue or discontinue RAS inhibitor therapy. After 3 years, mean eGFR was 12.6 ml/min/1.73 m² in the discontinuation group vs. 13.3 ml/min/1.73 m² in the continuation group (difference: –0.7; 95% CI: –2.5 to 1.0; P=0.42). End-stage kidney disease (ESKD) or renal-replacement therapy occurred in 62% vs. 56% of patients (HR: 1.28; 95% CI: 0.99–1.65). Adverse events—including cardiovascular events (108 vs. 88) and deaths (20 vs. 22)—were similar between groups. Discontinuation led to transient increases in blood pressure and proteinuria early in follow-up, but differences resolved with alternative antihypertensives. No significant differences were found in quality-of-life, exercise capacity, or hemoglobin levels. The findings suggest no clinically meaningful benefit in discontinuing RAS inhibitors among patients with advanced CKD, supporting their continued use unless contraindicated

This multicenter, open-label randomized controlled trial (STOP ACEi) investigated whether discontinuing renin–angiotensin system (RAS) inhibitors—ACE inhibitors and ARBs—in patients with advanced, progressive chronic kidney disease (CKD) would alter long-term kidney outcomes. A total of 411 adults (eGFR < 30 ml/min/1.73 m² with ≥2 ml/year decline over 2 years) were randomized to either continue or discontinue RAS inhibitor therapy. After 3 years, mean eGFR was 12.6 ml/min/1.73 m² in the discontinuation group vs. 13.3 ml/min/1.73 m² in the continuation group (difference: –0.7; 95% CI: –2.5 to 1.0; P=0.42). End-stage kidney disease (ESKD) or renal-replacement therapy occurred in 62% vs. 56% of patients (HR: 1.28; 95% CI: 0.99–1.65). Adverse events—including cardiovascular events (108 vs. 88) and deaths (20 vs. 22)—were similar between groups. Discontinuation led to transient increases in blood pressure and proteinuria early in follow-up, but differences resolved with alternative antihypertensives. No significant differences were found in quality-of-life, exercise capacity, or hemoglobin levels. The findings suggest no clinically meaningful benefit in discontinuing RAS inhibitors among patients with advanced CKD, supporting their continued use unless contraindicated