Ardabil University of Medical Sciences, Ardabil, Iran
Abstract: (251 Views)
IgA nephropathy, a leading form of primary glomerulonephritis globally, is marked by the accumulation of IgA-containing immune complexes in the glomerular mesangium, resulting in progressive kidney damage. The disease presents with diverse clinical features, including proteinuria, hematuria, and kidney failure, with varying progression among patients, making treatment particularly challenging. Due to its heterogeneity, treatment strategies are continually evolving, with a growing emphasis on personalized approaches guided by genetic data and biomarkers. This review highlights recent advancements in IgA nephropathy treatment, focusing on innovative therapies that have demonstrated potential in clinical trials or are under active investigation. Continued research and therapeutic breakthroughs hold promise for better symptom management and improved kidney outcomes.
Type of Study: Research |
Subject: General Received: 2025/04/20 | Accepted: 2025/01/1 | Published: 2025/01/1
References
1. Wyatt RJ, Julian BA. IgA nephropathy. New England Journal of Medicine. 2013;368(25):2402-14. [DOI:10.1056/NEJMra1206793] [PMID]
2. Rodrigues JC, Haas M, Reich HN. IgA nephropathy. Clinical Journal of the American Society of Nephrology. 2017;12(4):677-86. [DOI:10.2215/CJN.07420716] [PMID] []
3. Gutiérrez E, Carvaca-Fontán F, Luzardo L, Morales E, Alonso M, Praga M. A personalized update on IgA nephropathy: a new vision and new future challenges. Nephron. 2020;144(11):555-71. [DOI:10.1159/000509997] [PMID]
4. Lai KN. Pathogenesis of IgA nephropathy. Nature Reviews Nephrology. 2012;8(5):275-83. [DOI:10.1038/nrneph.2012.58] [PMID]
5. Boyd JK, Cheung CK, Molyneux K, Feehally J, Barratt J. An update on the pathogenesis and treatment of IgA nephropathy. Kidney international. 2012;81(9):833-43. [DOI:10.1038/ki.2011.501] [PMID]
6. Kdigo G. Work Group. KDIGO clinical practice guideline for glomerulonephritis. Kidney Int. 2012;2:139.
7. Coppo R. Corticosteroids in IgA nephropathy: lessons from recent studies. Journal of the American Society of Nephrology. 2017;28(1):25-33. [DOI:10.1681/ASN.2016060647] [PMID] []
8. Pozzi C. Pro: STOP immunosuppression in IgA nephropathy?. Nephrology Dialysis Transplantation. 2016;31(11):1766-70. [DOI:10.1093/ndt/gfw285] [PMID]
9. Lv J, Zhang H, Wong MG, Jardine MJ, Hladunewich M, Jha V, Monaghan H, Zhao M, Barbour S, Reich H, Cattran D. Effect of oral methylprednisolone on clinical outcomes in patients with IgA nephropathy: the TESTING randomized clinical trial. Jama. 2017;318(5):432-42. [DOI:10.1001/jama.2017.9362] [PMID] []
10. Vecchio LD, Rimoldi C, Pozzi C. Nefecon (targeted-release formulation-budesonide) for the treatment of IgA nephropathy. Future Rare Diseases. 2021;1(4):FRD18. [DOI:10.2217/frd-2021-0013]
11. Barratt J, Lafayette R, Kristensen J, Stone A, Cattran D, Floege J, Tesar V, Trimarchi H, Zhang H, Eren N, Paliege A. Results from part A of the multi-center, double-blind, randomized, placebo-controlled NefIgArd trial, which evaluated targeted-release formulation of budesonide for the treatment of primary immunoglobulin A nephropathy. Kidney international. 2023;103(2):391-402. [DOI:10.1016/j.kint.2022.09.017] [PMID]
12. Barratt J, Kristensen J, Pedersen C, Jerling M. Insights on Nefecon, a Targeted-Release Formulation of Budesonide and Its Selective Immunomodulatory Effects in Patients with IgA Nephropathy. Drug Design, Development and Therapy. 2024:3415-28. [DOI:10.2147/DDDT.S383138] [PMID] []
13. Zhang H, Rizk DV, Perkovic V, Maes B, Kashihara N, Rovin B, Trimarchi H, Sprangers B, Meier M, Kollins D, Papachristofi O. Results of a randomized double-blind placebo-controlled Phase 2 study propose iptacopan as an alternative complement pathway inhibitor for IgA nephropathy. Kidney international. 2024;105(1):189-99. [DOI:10.1016/j.kint.2023.09.027] [PMID]
14. Rizk DV, Rovin BH, Zhang H, Kashihara N, Maes B, Trimarchi H, Perkovic V, Meier M, Kollins D, Papachristofi O, Charney A. Targeting the alternative complement pathway with iptacopan to treat IgA nephropathy: design and rationale of the APPLAUSE-IgAN study. Kidney international reports. 2023;8(5):968-79. [DOI:10.1016/j.ekir.2023.01.041] [PMID] []
15. Barratt J, Leifke E, Whitaker S, DeTulleo L, Lafayette R. FP201 INTERIM RESULTS FROM AN ONGOING PHASE 2 STUDY EVALUATING THE USE OF A MASP-2 INHIBITOR FOR THE TREATMENT OF IGA NEPHROPATHY (IGAN). Nephrology Dialysis Transplantation. 2019;34(Supplement_1):gfz106-FP201. [DOI:10.1093/ndt/gfz106.FP201]
16. Lafayette R, Rovin B, Floege J, Tesar V, Zhang H, Barratt J. POS-132 trial design: phase 3 randomized, double-blind, placebo-controlled study of narsoplimab safety and efficacy in IGA nephropathy (artemis-IGAN). Kidney International Reports. 2022;7(2):S57. [DOI:10.1016/j.ekir.2022.01.144]
17. Lafayette RA, Canetta PA, Rovin BH, Appel GB, Novak J, Nath KA, Sethi S, Tumlin JA, Mehta K, Hogan M, Erickson S. A randomized, controlled trial of rituximab in IgA nephropathy with proteinuria and renal dysfunction. Journal of the American Society of Nephrology. 2017;28(4):1306-13. [DOI:10.1681/ASN.2016060640] [PMID] []
18. Mansour I, Murugapandian S, Tanriover B, Thajudeen B. Contemporary Monoclonal Antibody Utilization in Glomerular Diseases. Mayo Clinic Proceedings: Innovations, Quality & Outcomes. 2023;7(4):276-90. [DOI:10.1016/j.mayocpiqo.2023.04.009] [PMID] []
19. Yeo SC, Liew A, Barratt J. Emerging therapies in immunoglobulin A nephropathy. Nephrology. 2015;20(11):788-800. [DOI:10.1111/nep.12527] [PMID]
20. Rauen T, Floege J. Inflammation in IgA nephropathy. Pediatric Nephrology. 2017;32(12):2215-24. [DOI:10.1007/s00467-017-3628-1] [PMID]
21. Barratt J, Maes BD, Lin CJ, Wei X, Barbour S, Phoon RK, Kim SG, Tesar V, Floege J, Jha V, Lafayette RA. Atacicept 150 mg Reduces Serum Gd-IgA1, a Biomarker Associated with Long-Term Outcomes in IgA Nephropathy (IgAN): 36W Results from the Ph2b ORIGIN Study: SA-PO887. Journal of the American Society of Nephrology. 2023;34(11S):974-5. [DOI:10.1681/ASN.20233411S1974c]
22. Uriol-Rivera MG, Obrador-Mulet A, Juliá MR, Daza-Cajigal V, Delgado-Sanchez O, Garcia Alvarez A, Gomez-Lobon A, Carrillo-Garcia P, Saus-Sarrias C, Gómez-Cobo C, Ramis-Cabrer D. Sequential administration of paricalcitol followed by IL-17 blockade for progressive refractory IgA nephropathy patients. Scientific reports. 2024;14(1):4866. [DOI:10.1038/s41598-024-55425-7] [PMID] []
23. Barratt J, Rovin B, Wong MG, Alpers CE, Bieler S, He P, Inrig J, Komers R, Heerspink HJ, Mercer A, Noronha IL. IgA nephropathy patient baseline characteristics in the sparsentan PROTECT study. Kidney international reports. 2023;8(5):1043-56. [DOI:10.1016/j.ekir.2023.02.1086] [PMID] []
24. Liu LJ, Yang YZ, Shi SF, Bao YF, Yang C, Zhu SN, Sui GL, Chen YQ, Lv JC, Zhang H. Effects of hydroxychloroquine on proteinuria in IgA nephropathy: a randomized controlled trial. American Journal of Kidney Diseases. 2019;74(1):15-22. [DOI:10.1053/j.ajkd.2019.01.026] [PMID]
25. Heerspink HL, Jardine M, Kohan DE, Lafayette R, Levin A, Liew A, Zhang H, Sheth K, Camargo M, Jones-Burton C, King AJ. WCN23-1085 A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Atrasentan in Patients with IGA Nephropathy-The Align Study. Kidney International Reports. 2023;8(3):S279-80. [DOI:10.1016/j.ekir.2023.02.630]
26. Mareedu N, Errabelli P. WCN24-2352 Improved Proteinuria Reduction with the use of Sparsentan and Targeted Release Budesonide in advanced IgAN. Kidney International Reports. 2024;9(4):S188-9. [DOI:10.1016/j.ekir.2024.02.389]
27. Kiryluk K, Li Y, Scolari F, Sanna-Cherchi S, Choi M, Verbitsky M, Fasel D, Lata S, Prakash S, Shapiro S, Fischman C. Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens. Nature genetics. 2014;46(11):1187-96. [DOI:10.1038/ng.3118] [PMID] []
28. Tang Y, Zhu Y, He H, Peng Y, Hu P, Wu J, Sun W, Liu P, Xiao Y, Xu X, Wei M. Gut dysbiosis and intestinal barrier dysfunction promotes IgA nephropathy by increasing the production of Gd-IgA1. Frontiers in Medicine. 2022;9:944027. [DOI:10.3389/fmed.2022.944027] [PMID] []
29. Tumlin JA, Hennigar RA. Clinical presentation, natural history, and treatment of crescentic proliferative IgA nephropathy. InSeminars in nephrology 2004; 24(3): 256-268. [DOI:10.1016/j.semnephrol.2004.01.006] [PMID]
30. Coppo R. Treatment of IgA nephropathy: Recent advances and prospects. Nephrologie & therapeutique. 2018;14:S13-21. [DOI:10.1016/j.nephro.2018.02.010] [PMID]
31. Maixnerova D, Tesar V. Emerging modes of treatment of IgA nephropathy. International journal of molecular sciences. 2020;21(23):9064. [DOI:10.3390/ijms21239064] [PMID] []
32. Suzuki H. Biomarkers for IgA nephropathy on the basis of multi-hit pathogenesis. Clinical and experimental nephrology. 2019;23(1):26-31. [DOI:10.1007/s10157-018-1582-2] [PMID] []
33. Barratt J, Feehally J, Smith AC. Pathogenesis of IgA nephropathy. InSeminars in nephrology 2004: 24(3): 197-217. [DOI:10.1016/j.semnephrol.2004.01.002] [PMID]
34. Gale DP, Molyneux K, Wimbury D, Higgins P, Levine AP, Caplin B, Ferlin A, Yin P, Nelson CP, Stanescu H, Samani NJ. Galactosylation of IgA1 is associated with common variation in C1GALT1. Journal of the American Society of Nephrology. 2017;28(7):2158-66. [DOI:10.1681/ASN.2016091043] [PMID] []
35. Haniuda K, Gommerman JL, Reich HN. The microbiome and IgA nephropathy. InSeminars in Immunopathology. Springer Berlin Heidelberg. 2021; 43(5): 649-656. [DOI:10.1007/s00281-021-00893-6] [PMID]
36. Tang Y, He H, Hu P, Xu X. T lymphocytes in IgA nephropathy. Experimental and Therapeutic Medicine. 2020;20(1):186-94. [DOI:10.3892/etm.2020.8673]