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

BACKGROUND: IgA nephropathy (IgAN) 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 IgAN face a lifetime risk of end-stage kidney disease (ESKD), and an associated increase in mortality unless their annual estimated glomerular filtration rate (eGFR) decline is generally maintained at or below 1 mL/min/1.73 m2. The current standard of care in IgAN involves supportive chronic kidney disease therapies, notably renin-angiotensin-aldosterone system inhibitors (RAASi). Importantly, the long-term effectiveness of RAASi in slowing IgAN disease progression remains uncertain. Meta-analyses of randomized, controlled trials (RCTs) 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 RCTs 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 IgAN. RESULTS: A systematic literature review of four databases returned 171 studies published between January 2006 and November 2024. Of these, 10 included a control arm of participants with IgAN 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/1.73 m2 (95%CI: -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 IgAN, leaving patients at risk for ESKD. These findings underscore the need for disease-modifying therapies capable of effectively preserving kidney function, particularly in this predominantly young patient population.