Renin-Angiotensin System Inhibition in Advanced Chronic Kidney Disease

Area of Science:

• Nephrology
• Pharmacology

Background:

• Renin-angiotensin system (RAS) inhibitors, including ACE inhibitors and ARBs, are known to slow chronic kidney disease (CKD) progression.
• Some evidence suggests discontinuing RAS inhibitors in advanced CKD might improve or stabilize estimated glomerular filtration rate (eGFR).

Purpose of the Study:

• To investigate the effect of discontinuing RAS inhibitors versus continuing them in patients with advanced, progressive CKD on eGFR decline over three years.

Main Methods:

• A multicenter, open-label trial randomly assigned patients with advanced CKD (eGFR <30 ml/min/1.73 m²) to either discontinue or continue RAS inhibitor therapy.
• The primary outcome was eGFR at 3 years, excluding values post-renal-replacement therapy initiation.
• Secondary outcomes included end-stage kidney disease (ESKD), composite renal decline, hospitalizations, blood pressure, exercise capacity, and quality of life.

Main Results:

• After 3 years, the 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 (difference -0.7; P=0.42).
• ESKD or initiation of renal-replacement therapy occurred in 62% of the discontinuation group versus 56% of the continuation group (HR 1.28; 95% CI, 0.99 to 1.65).
• Adverse events, including cardiovascular events and deaths, were similar between groups.

Conclusions:

• Discontinuation of RAS inhibitors in advanced, progressive CKD was not associated with a significant difference in the long-term eGFR decline compared to continuation.
• The findings do not support routine discontinuation of RAS inhibitors in this patient population based on eGFR trajectory.