Effects of Therapies on Proteinuria and Estimated Glomerular Filtration Rate in IgA Nephropathy: Meta-Analysis of Randomized Trials

Background: Substantial advances have been made in therapeutics for IgA nephropathy. We conducted a systematic review and meta-analysis to evaluate the comparative efficacy and safety of existing and novel IgA nephropathy therapies. Methods: We searched MEDLINE and Embase databases from inception to May 21, 2025 for Phase 2b and 3 multi-center, randomized, placebo-controlled trials enrolling patients with IgA nephropathy that reported treatment effects on proteinuria and/or estimated glomerular filtration rate (eGFR) slope. Trials were categorized into four drug classes: Non-immunological therapies, corticosteroids, B-cell modulating agents and complement inhibitors. Treatment effects on proteinuria and eGFR slope were pooled overall and by drug class using random-effects meta-analysis. Results: Fourteen trials were identified of which proteinuria and eGFR outcomes were available in 13 trials (93%) and seven trials (50%) respectively. Pooled data demonstrated all therapies reduced proteinuria, although the magnitude of effect varied across classes: -34% with non-immunological therapies, -51% with corticosteroids, -45% with B-cell modulating agents and -35% with complement inhibitors ( P -heterogeneity <0.001). Data from trials reporting eGFR slope over a minimum of 12 months indicated benefits for all drug classes, but again with some evidence that effects varied by class. The absolute and relative effect on eGFR slope was 1.1mL/min/1.73m 2 per year and -28% with non-immunological therapies, 2.3mL/min/1.73m 2 per year and -52% with corticosteroids, and 4.3mL/min/1.73m 2 per year and -73% with B-cell modulating agents ( P -heterogeneity=0.03). Corticosteroids, particularly at higher doses, increased the risk of serious adverse events, but other drug classes were generally well tolerated. Longer-term data on clinical kidney outcomes and safety are awaited. Conclusions: All four drug classes improve kidney outcomes in IgA nephropathy, with some evidence of differential effects on proteinuria and eGFR slope. The varying mechanisms and effects of different therapies suggest a potential for combination therapy, although selection of the optimal combination of therapies for individuals remain to be determined.