Optimizing renin-angiotensin-aldosterone inhibition in advanced chronic kidney disease: balancing benefits and risks

Renin-angiotensin-aldosterone system inhibitors (RAASi), including angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs), are fundamental in chronic kidney disease (CKD) management, particularly in proteinuric conditions. However, their use in advanced CKD (eGFR <30 ml/min/1.73 m 2 ) remains debated because of risks of hyperkalaemia, acute kidney injury (AKI), and hypotension. This review evaluates the latest evidence, including the STOP-ACEi trial, to inform the risks and benefits of RAASi in advanced CKD.

The STOP-ACEi trial, a multicentre randomized controlled trial (RCT), investigated RAASi discontinuation in 411 patients with advanced CKD. After 3 years, discontinuation did not slow eGFR decline or reduce mortality, while continuation was associated with a numerical trend towards lower end-stage kidney disease (ESKD) rates. Meta-analyses also indicate that ACEi may offer superior kidney protection compared to ARBs, though both lower cardiovascular risk and this difference may not be clinically significant. Combination ACEi/ARB therapy provides no additional benefits and increases adverse events, such as hyperkalaemia and hypotension. Adjunct therapies like potassium binders and sodium-glucose cotransporter-2 (SGLT2) inhibitors may enable safer RAASi use in high-risk patients.

Current evidence supports RAASi continuation in most CKD patients, including those with advanced disease, unless contraindicated. Future studies should refine patient selection criteria and optimize adjunctive strategies to mitigate adverse effects.