A LARGE retrospective cohort study suggests that discontinuing renin–angiotensin system inhibitors (RAS inhibitors) after an acute decline in kidney function may be associated with worse long-term outcomes, challenging a common clinical practice.
RAS Inhibitors and Risk After eGFR Decline
RAS inhibitors are widely used to slow progression of chronic kidney disease (CKD), but clinicians often stop these medications when patients experience an early drop in estimated glomerular filtration rate (eGFR) following initiation. To investigate the consequences of this approach, Ku and colleagues conducted a target trial emulation study using linked electronic health record data from over 4,200 adults in Manitoba, Canada.
The study included patients who had newly started a RAS inhibitor between 2008 and 2021 and subsequently experienced a decline in eGFR of more than 15% within 90 days. Of these, approximately one-third discontinued therapy, while two-thirds continued treatment. Patients were followed for major outcomes including end-stage kidney disease (ESKD), death, major adverse cardiovascular events (MACEs), and acute kidney injury (AKI).
After 180 days, discontinuation of RAS inhibitors was associated with a significantly higher risk of both ESKD and mortality. Specifically, patients who stopped therapy had a 74% higher risk of progressing to ESKD and a 23% higher risk of death compared with those who continued treatment. In contrast, there were no statistically significant differences between groups in the risk of cardiovascular events or AKI.
Clinical Implications: Reconsidering Discontinuation Practices
These findings suggest that stopping RAS inhibitors in response to an acute decline in eGFR may inadvertently increase the risk of adverse kidney outcomes and death, without offering clear cardiovascular or safety benefits. The authors note that while an initial drop in eGFR is often interpreted as harmful, it may reflect haemodynamic changes rather than true kidney injury.
The study highlights the need for greater clarity around when RAS inhibitors should be discontinued and underscores the importance of supporting their continued use when appropriate. Further research is needed to better understand why discontinuation remains common in clinical practice and to develop strategies that promote persistence with these potentially life-prolonging therapies.
Reference
Ku E et al. Discontinuation of RAS inhibition after an acute decline in estimated glomerular filtration rate. JAMA Netw Open. 2026; 9;(3):e263680.
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