Journal Article

Comparative Efficacy and Safety of Pharmacological Interventions for IgA Nephropathy: A Systematic Review and Meta-Analysis

Alsharif, Rewa L., Alkuwaiti, Mohanad A., Alroshodi, Abdulaziz, Alshehri, Hussam J., Azzam, Ahmed Y., AlShammari, Reem F., Alabdulmohsen, Dalal M., Al-Harbi, Faisal A., Mobarki, Hanin J., Wasaya, Hanan I.

2025

Overview

Background and Objectives: IgA nephropathy represents the most prevalent form of primary glomerulonephritis around the world, with significant heterogeneity in management strategies and outcomes. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of pharmacological interventions for IgA nephropathy. Materials and Methods: We searched multiple databases through June 2025, identifying randomized controlled trials and observational studies evaluating pharmacological treatments in biopsy-proven IgA nephropathy. Primary outcomes included proteinuria reduction and estimated glomerular filtration ration (eGFR) preservation. Secondary outcomes included hard kidney endpoints and safety parameters. Random-effects meta-analyses were performed with comprehensive risk–benefit assessments. Results: Twenty-five studies were included. B-cell/plasma-cell-targeted therapies showed significant proteinuria reduction (−34.0% [95% CI: −45.7, −22.3%]), complement pathway inhibitors demonstrated superior eGFR preservation (+5.8 mL/min/1.73 m2/year [95% CI: 2.4, 9.2]). Systemic corticosteroids showed observed hard outcome benefits (HR 0.37 [95% CI: 0.26, 0.52]) but highest adverse event risk (RR 3.28 [95% CI: 2.11, 5.09]). Novel agents showed projected favorable effects (B-cell: HR 0.38; complement: HR 0.42) pending validation. Conclusions: Novel targeted therapies, especially B-cell/plasma-cell-targeted agents and complement pathway inhibitors, show promising risk–benefit profiles. However, longer-term data and standardized eGFR slope reporting are needed to confirm these findings compared to other immunosuppressive agents.

• Publisher: MDPI AG
• Subject: Adrenal Cortex Hormones - therapeutic use / Bias / Biopsy / chronic kidney disease / Clinical trials / Comparative analysis / complement pathway inhibitors / Evidence-based medicine / Glomerular Filtration Rate - drug effects / Glomerulonephritis, IGA - drug therapy / Humans / IgA nephropathy / Immunoglobulin A / Immunology / Immunosuppressive agents / immunosuppressors / Kidney diseases / Meta-analysis / Pathogenesis / plasma cell-targeted agents / Randomized Controlled Trials as Topic / Regression analysis / Steroids / Strategic planning (Business) / Systematic review / treatment / Treatment Outcome