The Impact of Renin–Angiotensin–Aldosterone System Inhibitors in IgA Nephropathy: A Meta-Analysis of Randomized Controlled Trials

Key Points – Standard-of-care therapy for IgA nephropathy has historically relied on renin–angiotensin–aldosterone system inhibitors. Current treatment goals aim to slow eGFR decline to reduce the risk of ESKD. Analysis of renin–angiotensin–aldosterone system inhibitor therapy alone found an eGFR decline of −4.5 ml/min per 1.73 m2 per year, which may not limit ESKD risk. Background – IgA nephropathy is a chronic autoimmune kidney disease characterized by deposition of immune complexes in the glomeruli, leading to inflammation and progressive, irreversible, kidney damage. Patients with IgA nephropathy face a lifetime risk of ESKD, and an associated increase in mortality unless their annual eGFR decline is generally maintained at or below 1 ml/min per 1.73 m2. The current standard of care in IgA nephropathy involves supportive CKD therapies, notably renin–angiotensin–aldosterone system inhibitors (RAASi). Importantly, the long-term effectiveness of RAASi in slowing IgA nephropathy disease progression remains uncertain. Meta-analyses of randomized controlled trials with comparable designs offer an opportunity to assess the impact of RAASi therapy on kidney function. Such analyses facilitate outcome comparisons across studies and may generate important evidence and contribute to informed clinical decision making. Methods – A meta-analysis was conducted using randomized controlled trials that reported the slope of eGFR decline and included one arm receiving maximally tolerated doses of RAASi. The analysis aimed to evaluate the impact of RAASi therapy on kidney function in high-risk patients with IgA nephropathy. Results – A systematic literature review of four databases returned 171 studies published between January 2006 and November 2024. Of these, ten included a control arm of participants with IgA nephropathy receiving maximized RAASi treatment (N=1366) and reported eGFR annualized slope decline. Meta-analysis of the pooled data demonstrated a mean annual eGFR slope decline of −4.5 ml/min per 1.73 m2 (95% confidence interval, −5.3 to −3.8) among participants treated with RAASi therapy alone. Conclusions – Treatment with maximally tolerated RAASi alone does not sufficiently slow the rate of eGFR decline in high-risk patients with IgA nephropathy, leaving patients at risk of ESKD. These findings underscore the need for disease-modifying therapies capable of effectively preserving kidney function, particularly in this predominantly young patient population. Copyright © 2026 by the American Society of Nephrology