Research progress in targeted therapy for immunoglobulin A nephropathy_West China Medical Journal

Authors：

ALUO Wusha ,  XIA Chengyun

Kidney Department, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P. R. China;

Corresponding?author：

XIA Chengyun, Email: dream870709@163.com

Keywords：

Immunoglobulin A nephropathy; targeted therapy; B cell-activating factor; research progress

DOI：

10.7507/1002-0179.202506151

Video：

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Abstract Full text Figures/Tables Video References Cited by

Immunoglobulin A nephropathy is a common primary glomerular disease, and its targeted therapy focuses on key links such as upstream regulation of galactose-deficient immunoglobulin A1 production, blocking immune complex deposition, inhibiting complement activation, and downstream inflammatory responses. This article systematically reviews the latest research progress of targeted therapeutic drugs based on the pathogenesis of immunoglobulin A nephropathy, summarizes their mechanisms of action and clinical research evidence, and explores the current challenges and future development directions, in order to provide references for clinical practice and research.

Citation： ALUO Wusha, XIA Chengyun. Research progress in targeted therapy for immunoglobulin A nephropathy. West China Medical Journal, 2026, 41(2): 328-333. doi: 10.7507/1002-0179.202506151 Copy

1.	Wyatt RJ, Julian BA. IgA nephropathy. N Engl J Med, 2013, 368(25): 2402-2414.
2.	Filippone EJ, Gulati R, Farber JL. Contemporary review of IgA nephropathy. Front Immunol, 2024, 15: 1436923.
3.	Pitcher D, Braddon F, Hendry B, et al. Long-term outcomes in IgA nephropathy. Clin J Am Soc Nephrol, 2023, 18(6): 727-738.
4.	Filippone EJ, Gulati R, Farber JL. The road ahead: emerging therapies for primary IgA nephropathy. Front Nephrol, 2025, 5: 1545329.
5.	Lv J, Wong MG, Hladunewich MA, et al. Effect of oral methylprednisolone on decline in kidney function or kidney failure in patients with IgA nephropathy: the TESTING randomized clinical trial. JAMA, 2022, 327(19): 1888-1898.
6.	Zhang YM, Lv JC, Wong MG, et al. Glucocorticoids for IgA nephropathy-pro. Kidney Int, 2023, 103(4): 666-669.
7.	Rajasekaran A, Green TJ, Renfrow MB, et al. Current understanding of complement proteins as therapeutic targets for the treatment of immunoglobulin A nephropathy. Drugs, 2023, 83(16): 1475-1499.
8.	李湛, 解新芳, 張雪, 等. IgA 腎病患者血漿抗糖抗體的測定及其與臨床病理指標的相關性. 中華腎臟病雜志, 2019, 35(2): 81-87.
9.	Gesualdo L, Di Leo V, Coppo R. The mucosal immune system and IgA nephropathy. Semin Immunopathol, 2021, 43(5): 657-668.
10.	Gan T, Li Y, Zhou XJ, et al. Immunoproteasome in IgA nephropathy: state-of-art and future perspectives. Int J Biol Sci, 2020, 16(14): 2518-2526.
11.	Fellstr?m BC, Barratt J, Cook H, et al. Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN): a double-blind, randomised, placebo-controlled phase 2b trial. Lancet, 2017, 389(10084): 2117-2127.
12.	Smerud HK, Bárány P, Lindstr?m K, et al. New treatment for IgA nephropathy: enteric budesonide targeted to the ileocecal region ameliorates proteinuria. Nephrol Dial Transplant, 2011, 26(10): 3237-3242.
13.	Barratt J, Lafayette R, Kristensen J, et al. 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 Int, 2023, 103(2): 391-402.
14.	Lafayette R, Kristensen J, Stone A, et al. Efficacy and safety of a targeted-release formulation of budesonide in patients with primary IgA nephropathy (NefIgArd): 2-year results from a randomised phase 3 trial. Lancet, 2023, 402(10405): 859-870.
15.	Raje AA, Deshpande RD, Pathade VV, et al. Evaluation of separate role of intestine and liver in first pass metabolism of budesonide in rat. Xenobiotica, 2018, 48(12): 1206-1214.
16.	Edsb?cker S, Larsson P, Wollmer P. Gut delivery of budesonide, a locally active corticosteroid, from plain and controlled-release capsules. Eur J Gastroenterol Hepatol, 2002, 14(12): 1357-1362.
17.	Myette JR, Kano T, Suzuki H, et al. A proliferation inducing ligand (APRIL) targeted antibody is a safe and effective treatment of murine IgA nephropathy. Kidney Int, 2019, 96(1): 104-116.
18.	McCarthy DD, Chiu S, Gao Y, et al. BAFF induces a hyper-IgA syndrome in the intestinal lamina propria concomitant with IgA deposition in the kidney independent of LIGHT. Cell Immunol, 2006, 241(2): 85-94.
19.	McCarthy DD, Kujawa J, Wilson C, et al. Mice overexpressing BAFF develop a commensal flora-dependent, IgA-associated nephropathy. J Clin Invest, 2011, 121(10): 3991-4002.
20.	Xin G, Shi W, Xu LX, et al. Serum BAFF is elevated in patients with IgA nephropathy and associated with clinical and histopathological features. J Nephrol, 2013, 26(4): 683-690.
21.	Zhai YL, Zhu L, Shi SF, et al. Increased APRIL expression induces IgA1 aberrant glycosylation in IgA nephropathy. Medicine (Baltimore), 2016, 95(11): e3099.
22.	Mathur M, Barratt J, Chacko B, et al. A phase 2 trial of sibeprenlimab in patients with IgA nephropathy. N Engl J Med, 2024, 390(1): 20-31.
23.	Barratt J, Kim SG, Agha I, et al. WCN23-1175 updated interim results of a phase 1/2 study of BION-1301 in patients with iga nephropathy. Kidney Int Rep, 2023, 8(3): S280-S281.
24.	Kaegi C, Steiner UC, Wuest B, et al. Systematic review of safety and efficacy of atacicept in treating immune-mediated disorders. Front Immunol, 2020, 11: 433.
25.	Barratt J, Tumlin J, Suzuki Y, et al. Randomized phase II JANUS study of atacicept in patients with IgA nephropathy and persistent proteinuria. Kidney Int Rep, 2022, 7(8): 1831-1841.
26.	Lafayette R, Barbour S, Israni R, et al. A phase 2b, randomized, double-blind, placebo-controlled, clinical trial of atacicept for treatment of IgA nephropathy. Kidney Int, 2024, 105(6): 1306-1315.
27.	Barratt J, Barbour SJ, Brenner RM, et al. Long-term results from an open-label extension study of atacicept for the treatment of IgA nephropathy. J Am Soc Nephrol, 2025, 36(4): 679-687.
28.	Gao S, Yang C, Huang B, et al. Comparative efficacy and safety of different recommended doses of telitacicept in patients with systemic lupus erythematosus in China: a systematic review and meta-analysis. Front Immunol, 2025, 15: 1472292.
29.	Lv J, Liu L, Hao C, et al. Randomized phase 2 trial of telitacicept in patients with IgA nephropathy with persistent proteinuria. Kidney Int Rep, 2022, 8(3): 499-506.
30.	Pastrana DV. mSphere of influence: it’s not me, it’s you-how donor factors influence kidney transplant outcomes. mSphere, 2020, 5(1): e00964-19.
31.	Schrezenmeier E, Jayne D, D?rner T. Targeting B cells and plasma cells in glomerular diseases: translational perspectives. J Am Soc Nephrol, 2018, 29(3): 741-758.
32.	Floege J, Lafayette R, Barratt J, et al. Randomized, double-blind, placebo-controlled phase 2a study assessing the efficacy and safety of felzartamab for IgA nephropathy. Kidney Int, 2025, 108(4): 695-706.
33.	Hartono C, Chung M, Perlman AS, et al. Bortezomib for reduction of proteinuria in IgA nephropathy. Kidney Int Rep, 2018, 3(4): 861-866.
34.	Mócsai A, Ruland J, Tybulewicz VL. The SYK tyrosine kinase: a crucial player in diverse biological functions. Nat Rev Immunol, 2010, 10(6): 387-402.
35.	Kim MJ, McDaid JP, McAdoo SP, et al. Spleen tyrosine kinase is important in the production of proinflammatory cytokines and cell proliferation in human mesangial cells following stimulation with IgA1 isolated from IgA nephropathy patients. J Immunol, 2012, 189(7): 3751-3758.
36.	Park S, Yang SH, Jeong CW, et al. RNA-Seq profiling of microdissected glomeruli identifies potential biomarkers for human IgA nephropathy. Am J Physiol Renal Physiol, 2020, 319(5): F809-F821.
37.	Tam FWK, Tumlin J, Barratt J, et al. Randomized trial on the effect of an oral spleen tyrosine kinase inhibitor in the treatment of IgA nephropathy. Kidney Int Rep, 2023, 8(12): 2546-2556.
38.	Floege J, Daha MR. IgA nephropathy: new insights into the role of complement. Kidney Int, 2018, 94(1): 16-18.
39.	Lafayette RA, Rovin BH, Reich HN, et al. Safety, tolerability and efficacy of narsoplimab, a novel MASP-2 inhibitor for the treatment of IgA nephropathy. Kidney Int Rep, 2020, 5(11): 2032-2041.
40.	Zhang H, Rizk DV, Perkovic V, et al. Results of a randomized double-blind placebo-controlled phase 2 study propose iptacopan as an alternative complement pathway inhibitor for IgA nephropathy. Kidney Int, 2024, 105(1): 189-199.
41.	Perkovic V, Barratt J, Rovin B, et al. Alternative complement pathway inhibition with iptacopan in IgA nephropathy. N Engl J Med, 2025, 392(6): 531-543.
42.	Paunas TIF, Finne K, Leh S, et al. Glomerular abundance of complement proteins characterized by proteomic analysis of laser-captured microdissected glomeruli associates with progressive disease in IgA nephropathy. Clin Proteomics, 2017, 14: 30.
43.	Lafayette R, Tumlin J, Fenoglio R, et al. Efficacy and safety of ravulizumab in IgA nephropathy: a phase 2 randomized double-blind placebo-controlled trial. J Am Soc Nephrol, 2025, 36(4): 645-656.
44.	Barratt J, Liew A, Yeo SC, et al. Phase 2 trial of cemdisiran in adult patients with IgA nephropathy: a randomized controlled trial. Clin J Am Soc Nephrol, 2024, 19(4): 452-462.
45.	Bruchfeld A, Magin H, Nachman P, et al. C5a receptor inhibitor avacopan in immunoglobulin A nephropathy-an open-label pilot study. Clin Kidney J, 2022, 15(5): 922-928.
46.	Chen B, Zhu Y, Yang Y, et al. Efficacy and safety of agents for IgA nephropathy: a network meta-analysis of randomized controlled trials. Front Med (Lausanne), 2025, 12: 1515723.
47.	Zhang X, Wang Y, Yarbrough J, et al. Safety, pharmacokinetics, and pharmacodynamics of subcutaneous sibeprenlimab in healthy participants. Clin Pharmacol Drug Dev, 2023, 12(12): 1211-1220.
48.	Ispasanie E, Muri L, Schmid M, et al. In vaccinated individuals serum bactericidal activity against B meningococci is abrogated by C5 inhibition but not by inhibition of the alternative complement pathway. Front Immunol, 2023, 14: 1180833.
49.	Lafayette RA, Canetta PA, Rovin BH, et al. A randomized, controlled trial of rituximab in IgA nephropathy with proteinuria and renal dysfunction. J Am Soc Nephrol, 2017, 28(4): 1306-1313.

1. Wyatt RJ, Julian BA. IgA nephropathy. N Engl J Med, 2013, 368(25): 2402-2414.
2. Filippone EJ, Gulati R, Farber JL. Contemporary review of IgA nephropathy. Front Immunol, 2024, 15: 1436923.
3. Pitcher D, Braddon F, Hendry B, et al. Long-term outcomes in IgA nephropathy. Clin J Am Soc Nephrol, 2023, 18(6): 727-738.
4. Filippone EJ, Gulati R, Farber JL. The road ahead: emerging therapies for primary IgA nephropathy. Front Nephrol, 2025, 5: 1545329.
5. Lv J, Wong MG, Hladunewich MA, et al. Effect of oral methylprednisolone on decline in kidney function or kidney failure in patients with IgA nephropathy: the TESTING randomized clinical trial. JAMA, 2022, 327(19): 1888-1898.
6. Zhang YM, Lv JC, Wong MG, et al. Glucocorticoids for IgA nephropathy-pro. Kidney Int, 2023, 103(4): 666-669.
7. Rajasekaran A, Green TJ, Renfrow MB, et al. Current understanding of complement proteins as therapeutic targets for the treatment of immunoglobulin A nephropathy. Drugs, 2023, 83(16): 1475-1499.
8. 李湛, 解新芳, 張雪, 等. IgA 腎病患者血漿抗糖抗體的測定及其與臨床病理指標的相關性. 中華腎臟病雜志, 2019, 35(2): 81-87.
9. Gesualdo L, Di Leo V, Coppo R. The mucosal immune system and IgA nephropathy. Semin Immunopathol, 2021, 43(5): 657-668.
10. Gan T, Li Y, Zhou XJ, et al. Immunoproteasome in IgA nephropathy: state-of-art and future perspectives. Int J Biol Sci, 2020, 16(14): 2518-2526.
11. Fellstr?m BC, Barratt J, Cook H, et al. Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN): a double-blind, randomised, placebo-controlled phase 2b trial. Lancet, 2017, 389(10084): 2117-2127.
12. Smerud HK, Bárány P, Lindstr?m K, et al. New treatment for IgA nephropathy: enteric budesonide targeted to the ileocecal region ameliorates proteinuria. Nephrol Dial Transplant, 2011, 26(10): 3237-3242.
13. Barratt J, Lafayette R, Kristensen J, et al. 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 Int, 2023, 103(2): 391-402.
14. Lafayette R, Kristensen J, Stone A, et al. Efficacy and safety of a targeted-release formulation of budesonide in patients with primary IgA nephropathy (NefIgArd): 2-year results from a randomised phase 3 trial. Lancet, 2023, 402(10405): 859-870.
15. Raje AA, Deshpande RD, Pathade VV, et al. Evaluation of separate role of intestine and liver in first pass metabolism of budesonide in rat. Xenobiotica, 2018, 48(12): 1206-1214.
16. Edsb?cker S, Larsson P, Wollmer P. Gut delivery of budesonide, a locally active corticosteroid, from plain and controlled-release capsules. Eur J Gastroenterol Hepatol, 2002, 14(12): 1357-1362.
17. Myette JR, Kano T, Suzuki H, et al. A proliferation inducing ligand (APRIL) targeted antibody is a safe and effective treatment of murine IgA nephropathy. Kidney Int, 2019, 96(1): 104-116.
18. McCarthy DD, Chiu S, Gao Y, et al. BAFF induces a hyper-IgA syndrome in the intestinal lamina propria concomitant with IgA deposition in the kidney independent of LIGHT. Cell Immunol, 2006, 241(2): 85-94.
19. McCarthy DD, Kujawa J, Wilson C, et al. Mice overexpressing BAFF develop a commensal flora-dependent, IgA-associated nephropathy. J Clin Invest, 2011, 121(10): 3991-4002.
20. Xin G, Shi W, Xu LX, et al. Serum BAFF is elevated in patients with IgA nephropathy and associated with clinical and histopathological features. J Nephrol, 2013, 26(4): 683-690.
21. Zhai YL, Zhu L, Shi SF, et al. Increased APRIL expression induces IgA1 aberrant glycosylation in IgA nephropathy. Medicine (Baltimore), 2016, 95(11): e3099.
22. Mathur M, Barratt J, Chacko B, et al. A phase 2 trial of sibeprenlimab in patients with IgA nephropathy. N Engl J Med, 2024, 390(1): 20-31.
23. Barratt J, Kim SG, Agha I, et al. WCN23-1175 updated interim results of a phase 1/2 study of BION-1301 in patients with iga nephropathy. Kidney Int Rep, 2023, 8(3): S280-S281.
24. Kaegi C, Steiner UC, Wuest B, et al. Systematic review of safety and efficacy of atacicept in treating immune-mediated disorders. Front Immunol, 2020, 11: 433.
25. Barratt J, Tumlin J, Suzuki Y, et al. Randomized phase II JANUS study of atacicept in patients with IgA nephropathy and persistent proteinuria. Kidney Int Rep, 2022, 7(8): 1831-1841.
26. Lafayette R, Barbour S, Israni R, et al. A phase 2b, randomized, double-blind, placebo-controlled, clinical trial of atacicept for treatment of IgA nephropathy. Kidney Int, 2024, 105(6): 1306-1315.
27. Barratt J, Barbour SJ, Brenner RM, et al. Long-term results from an open-label extension study of atacicept for the treatment of IgA nephropathy. J Am Soc Nephrol, 2025, 36(4): 679-687.
28. Gao S, Yang C, Huang B, et al. Comparative efficacy and safety of different recommended doses of telitacicept in patients with systemic lupus erythematosus in China: a systematic review and meta-analysis. Front Immunol, 2025, 15: 1472292.
29. Lv J, Liu L, Hao C, et al. Randomized phase 2 trial of telitacicept in patients with IgA nephropathy with persistent proteinuria. Kidney Int Rep, 2022, 8(3): 499-506.
30. Pastrana DV. mSphere of influence: it’s not me, it’s you-how donor factors influence kidney transplant outcomes. mSphere, 2020, 5(1): e00964-19.
31. Schrezenmeier E, Jayne D, D?rner T. Targeting B cells and plasma cells in glomerular diseases: translational perspectives. J Am Soc Nephrol, 2018, 29(3): 741-758.
32. Floege J, Lafayette R, Barratt J, et al. Randomized, double-blind, placebo-controlled phase 2a study assessing the efficacy and safety of felzartamab for IgA nephropathy. Kidney Int, 2025, 108(4): 695-706.
33. Hartono C, Chung M, Perlman AS, et al. Bortezomib for reduction of proteinuria in IgA nephropathy. Kidney Int Rep, 2018, 3(4): 861-866.
34. Mócsai A, Ruland J, Tybulewicz VL. The SYK tyrosine kinase: a crucial player in diverse biological functions. Nat Rev Immunol, 2010, 10(6): 387-402.
35. Kim MJ, McDaid JP, McAdoo SP, et al. Spleen tyrosine kinase is important in the production of proinflammatory cytokines and cell proliferation in human mesangial cells following stimulation with IgA1 isolated from IgA nephropathy patients. J Immunol, 2012, 189(7): 3751-3758.
36. Park S, Yang SH, Jeong CW, et al. RNA-Seq profiling of microdissected glomeruli identifies potential biomarkers for human IgA nephropathy. Am J Physiol Renal Physiol, 2020, 319(5): F809-F821.
37. Tam FWK, Tumlin J, Barratt J, et al. Randomized trial on the effect of an oral spleen tyrosine kinase inhibitor in the treatment of IgA nephropathy. Kidney Int Rep, 2023, 8(12): 2546-2556.
38. Floege J, Daha MR. IgA nephropathy: new insights into the role of complement. Kidney Int, 2018, 94(1): 16-18.
39. Lafayette RA, Rovin BH, Reich HN, et al. Safety, tolerability and efficacy of narsoplimab, a novel MASP-2 inhibitor for the treatment of IgA nephropathy. Kidney Int Rep, 2020, 5(11): 2032-2041.
40. Zhang H, Rizk DV, Perkovic V, et al. Results of a randomized double-blind placebo-controlled phase 2 study propose iptacopan as an alternative complement pathway inhibitor for IgA nephropathy. Kidney Int, 2024, 105(1): 189-199.
41. Perkovic V, Barratt J, Rovin B, et al. Alternative complement pathway inhibition with iptacopan in IgA nephropathy. N Engl J Med, 2025, 392(6): 531-543.
42. Paunas TIF, Finne K, Leh S, et al. Glomerular abundance of complement proteins characterized by proteomic analysis of laser-captured microdissected glomeruli associates with progressive disease in IgA nephropathy. Clin Proteomics, 2017, 14: 30.
43. Lafayette R, Tumlin J, Fenoglio R, et al. Efficacy and safety of ravulizumab in IgA nephropathy: a phase 2 randomized double-blind placebo-controlled trial. J Am Soc Nephrol, 2025, 36(4): 645-656.
44. Barratt J, Liew A, Yeo SC, et al. Phase 2 trial of cemdisiran in adult patients with IgA nephropathy: a randomized controlled trial. Clin J Am Soc Nephrol, 2024, 19(4): 452-462.
45. Bruchfeld A, Magin H, Nachman P, et al. C5a receptor inhibitor avacopan in immunoglobulin A nephropathy-an open-label pilot study. Clin Kidney J, 2022, 15(5): 922-928.
46. Chen B, Zhu Y, Yang Y, et al. Efficacy and safety of agents for IgA nephropathy: a network meta-analysis of randomized controlled trials. Front Med (Lausanne), 2025, 12: 1515723.
47. Zhang X, Wang Y, Yarbrough J, et al. Safety, pharmacokinetics, and pharmacodynamics of subcutaneous sibeprenlimab in healthy participants. Clin Pharmacol Drug Dev, 2023, 12(12): 1211-1220.
48. Ispasanie E, Muri L, Schmid M, et al. In vaccinated individuals serum bactericidal activity against B meningococci is abrogated by C5 inhibition but not by inhibition of the alternative complement pathway. Front Immunol, 2023, 14: 1180833.
49. Lafayette RA, Canetta PA, Rovin BH, et al. A randomized, controlled trial of rituximab in IgA nephropathy with proteinuria and renal dysfunction. J Am Soc Nephrol, 2017, 28(4): 1306-1313.

West China Medical Journal

Research progress in targeted therapy for immunoglobulin A nephropathy

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