{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:08:46Z","timestamp":1782086926647,"version":"3.54.5"},"reference-count":59,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deanship of Graduate Studies and Scientific Research at Qassim University","award":["QU-APC-2025"],"award-info":[{"award-number":["QU-APC-2025"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>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\u2013benefit assessments. Results: Twenty-five studies were included. B-cell\/plasma-cell-targeted therapies showed significant proteinuria reduction (\u221234.0% [95% CI: \u221245.7, \u221222.3%]), 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\u2013benefit profiles. However, longer-term data and standardized eGFR slope reporting are needed to confirm these findings compared to other immunosuppressive agents.<\/jats:p>","DOI":"10.3390\/medicina61122233","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T13:42:52Z","timestamp":1765978972000},"page":"2233","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Comparative Efficacy and Safety of Pharmacological Interventions for IgA Nephropathy: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6087-4561","authenticated-orcid":false,"given":"Abdulaziz","family":"Alroshodi","sequence":"first","affiliation":[{"name":"Department of Medicine, College of Medicine, Qassim University, Buraydah 52571, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7741-4670","authenticated-orcid":false,"given":"Faisal A.","family":"Al-Harbi","sequence":"additional","affiliation":[{"name":"College of Medicine, Qassim University, Buraydah 52571, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5412-046X","authenticated-orcid":false,"given":"Mohanad A.","family":"Alkuwaiti","sequence":"additional","affiliation":[{"name":"College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalal M.","family":"Alabdulmohsen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Al Ahsa Health Cluster, Al Ahsa 31982, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanin J.","family":"Mobarki","sequence":"additional","affiliation":[{"name":"College of Medicine, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1324-609X","authenticated-orcid":false,"given":"Reem F.","family":"AlShammari","sequence":"additional","affiliation":[{"name":"College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rewa L.","family":"Alsharif","sequence":"additional","affiliation":[{"name":"College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah 11481, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanan I.","family":"Wasaya","sequence":"additional","affiliation":[{"name":"College of Medicine, Batterjee Medical College, Jeddah 21442, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2659-0155","authenticated-orcid":false,"given":"Hussam J.","family":"Alshehri","sequence":"additional","affiliation":[{"name":"College of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4256-0159","authenticated-orcid":false,"given":"Ahmed Y.","family":"Azzam","sequence":"additional","affiliation":[{"name":"Clinical Research and Clinical Artificial Intelligence, ASIDE Healthcare, Lewes, DE 19958, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,17]]},"reference":[{"key":"ref_1","unstructured":"Rout, P., Limaiem, F., and Hashmi, M.F. 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