Causal Effects of Renin–Angiotensin–Aldosterone System Inhibition on Renal Function in Patients With Chronic Kidney Disease: A Quasi‐Experimental Study

Renin-angiotensin-aldosterone system inhibitors are widely prescribed for chronic kidney disease, but their causal effect on kidney function remains uncertain. This study investigated the impact of starting renin-angiotensin blockade on renal function in adults with kidney disease. A retrospective cohort study was conducted in Korea using a quasi-experimental staggered difference-in-differences design with propensity score matching to estimate time-varying treatment effects. Overall, 1,204 adults (375 treated and 829 contemporaneous not-yet-treated controls) were followed for 3 years. Initiation of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers was recorded, and treatment exposure was categorized monthly. The primary outcome was a change in estimated glomerular filtration rate after initiation, evaluated over sequential intervals up to 12 months. The overall average treatment effect of two-way fixed effects model was not statistically significant (-1.47 mL/min/1.73 m²; p = 0.33). However, initiation was associated with an immediate and significant decline in eGFR at event time 0 (estimate: -3.87 mL/min/1.73 m², p < 0.05) and at event time 1 and 3 (p < 0.05). Beyond these early intervals, there was no evidence of progressive deterioration in kidney function during the 1-year follow-up. Declines following initiation of renin-angiotensin blockade are early, transient, and primarily hemodynamic in nature rather than reflective of structural kidney injury. Importantly, this quasi-experimental analysis of real-world data reproduced the findings of randomized trials, reinforcing current guideline recommendations to continue therapy in chronic kidney disease provided that reduction in filtration rate remains below the accepted threshold of 30%.