The Impact of Renin-Angiotensin Aldosterone System Inhibitors in IgA Nephropathy: A Meta-Analysis of Randomized Controlled Trials
In brief
Maximized RAAS inhibitors fail to slow IgA nephropathy, eGFR drops 4.5 mL/min yearly
A meta-analysis of ten randomized trials involving 1,366 high-risk IgA nephropathy patients found that even maximally tolerated RAAS blockade did not meaningfully reduce the annual decline in kidney function, with an average loss of about 4.5 mL/min/1.73 m². The result highlights the urgent need for disease-modifying treatments beyond standard RAAS inhibition.
- Journal
- Clinical journal of the American Society of Nephrology : CJASN (Q1)
- Published
- 12 August 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Anjay Rastogi, Mrinalini Sarkar, Kosuke Kawai, Gabriel Munoz, Lewis Simon, Michelle Hwang, et al.
- PMID
- 42584957
- DOI
- 10.2215/CJN.0000001130
Why clinicians should know about it
- Picked for Nephrology (top studies of the week, 16 August 2026): RAASi alone does not slow eGFR decline in IgAN
- Picked for Epidemiology (top studies of the week, 16 August 2026).
Abstract
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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.