Advances in Multitarget Therapeutic Approaches for Immune-Mediated Glomerular Diseases

. 2025 Feb 06 ; 15 (2) : . [epub] 20250206

Status PubMed-not-MEDLINE Jazyk angličtina Země Švýcarsko Médium electronic

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/pmid40003652

Glomerulonephritis (GN) encompasses a diverse group of immune-mediated diseases that damage the glomerular component of the nephron. While kidney biopsy remains the gold standard for diagnosis, it often fails to provide adequate insight into the underlying etiology of GN. Current classification systems have limited our understanding of the disease's pathophysiology and hinder the development of targeted therapies. Immunosuppressive treatments, such as glucocorticoids, calcineurin inhibitors, cyclophosphamide, and rituximab, remain the mainstay of therapy, though many patients fail to achieve remission or experience significant adverse effects. Moreover, the complex and multifactorial nature of GN pathogenesis calls for more refined therapeutic approaches. In recent years, multitarget therapies-combining different immunosuppressive agents targeting distinct immune pathways-have emerged as promising alternatives. Evidence suggests that multitarget therapy may offer superior outcomes compared to standard treatments. Despite early success, further studies are needed to optimize these regimens, reduce toxicity, and extend benefits to a broader range of GN patients. The development of personalized, biomarker-driven treatments, potentially leveraging innovative drug delivery systems and targeted biologics, holds promise for transforming GN care in the future.

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Fervenza F.C., Appel G.B., Barbour S.J., Rovin B.H., Lafayette R.A., Aslam N., Jefferson J.A., Gipson P.E., Rizk D.V., Sedor J.R., et al. Rituximab or Cyclosporine in the Treatment of Membranous Nephropathy. N. Engl. J. Med. 2019;381:36–46. doi: 10.1056/NEJMoa1814427. PubMed DOI

Scolari F., Delbarba E., Santoro D., Gesualdo L., Pani A., Dallera N., Mani L.-Y., Santostefano M., Feriozzi S., Quaglia M., et al. Rituximab or cyclophosphamide in the treatment of membranous nephropathy: The RI-CYCLO randomized trial. J. Am. Soc. Nephrol. 2021;32:972–982. doi: 10.1681/ASN.2020071091. PubMed DOI PMC

Kostopoulou M., Fanouriakis A., Cheema K., Boletis J., Bertsias G., Jayne D., Boumpas D.T. Management of lupus nephritis: A systematic literature review informing the 2019 update of the joint EULAR and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations. RMD Open. 2020;6:e001263. doi: 10.1136/rmdopen-2020-001263. PubMed DOI PMC

Lv J., Wong M.G., Hladunewich M.A., Jha V., Hooi L.S., Monaghan H., Zhao M., Barbour S., Jardine M.J., Reich H.N., 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;327:1888–1898. doi: 10.1001/jama.2022.5368. PubMed DOI PMC

Samman K.N., Ross C., Pagnoux C., Makhzoum J.P. Update in the Management of ANCA-Associated Vasculitis: Recent Developments and Future Perspectives. Int. J. Rheumatol. 2021;2021:5534851. doi: 10.1155/2021/5534851. PubMed DOI PMC

Gkrania-Klotsas E., Kumararatne D.S. Serious Infectious Complications After Rituximab Therapy in Patients with Autoimmunity: Is This the Final Word? Clin. Infect. Dis. 2021;72:738–742. doi: 10.1093/cid/ciaa131. PubMed DOI

Meliambro K., He J.C., Campbell K.N. Podocyte-targeted therapies—Progress and future directions. Nat. Rev. Nephrol. 2024;20:643–658. doi: 10.1038/s41581-024-00843-z. PubMed DOI

Huang Y., Ning X., Ahrari S., Cai Q., Rajora N., Saxena R., Yu M., Zheng J. Physiological principles underlying the kidney targeting of renal nanomedicines. Nat. Rev. Nephrol. 2024;20:354–370. doi: 10.1038/s41581-024-00819-z. PubMed DOI

Wang L., Wang J., Xu A., Wei L., Pei M., Shen T., Xian X., Yang K., Fei L., Pan Y., et al. Future embracing: Exosomes driving a revolutionary approach to the diagnosis and treatment of idiopathic membranous nephropathy. J. Nanobiotechnol. 2024;22:472. doi: 10.1186/s12951-024-02633-y. PubMed DOI PMC

Hariharan S., Israni A.K., Danovitch G. Long-term survival after kidney transplantation. N. Engl. J. Med. 2021;385:729–743. doi: 10.1056/NEJMra2014530. PubMed DOI

[(accessed on 6 January 2025)]; Available online: https://usrds-adr.niddk.nih.gov/2023/end-stage-renal-disease/7-transplantation.

Mahajan A., Amelio J., Gairy K., Kaur G., Levy R.A., Roth D., Bass D. Systemic lupus erythematosus, lupus nephritis and end-stage renal disease: A pragmatic review mapping disease severity and progression. Lupus. 2020;29:1011–1020. doi: 10.1177/0961203320932219. PubMed DOI PMC

Liu Z., Zhang H., Liu Z., Xing C., Fu P., Ni Z., Chen J., Lin H., Liu F., He Y., et al. Multitarget therapy for induction treatment of lupus nephritis: A randomized trial. Ann. Intern. Med. 2015;162:18–26. doi: 10.7326/M14-1030. PubMed DOI

Zhang H., Liu Z., Zhou M., Liu Z., Chen J., Xing C., Lin H., Ni Z., Fu P., Liu F., et al. Multitarget Therapy for Maintenance Treatment of Lupus Nephritis. J. Am. Soc. Nephrol. 2017;28:3671–3678. doi: 10.1681/ASN.2017030263. PubMed DOI PMC

Jiang N., Jin S., Yu C., Zhao J., Wang Q., Tian X., Li M., Zeng X. Efficacy and safety of immunosuppressive agents for adults with lupus nephritis: A systematic review and network meta-analysis. Front. Immunol. 2023;14:1232244. doi: 10.3389/fimmu.2023.1232244. PubMed DOI PMC

Tian G.Q., Li Z.Q. Efficacy and safety of biologics, multitarget therapy, and standard therapy for lupus nephritis: A systematic review and network meta-analysis. Ren. Fail. 2024;46:2395451. doi: 10.1080/0886022X.2024.2395451. PubMed DOI PMC

New ACR Guideline Summary Provides Guidance to Screen, Treat, and Manage Lupus Nephritis. News Release. American College of Rheumatology. 18 November 2024. [(accessed on 22 November 2024)]. Available online: https://rheumatology.org/press-releases/new-acr-guideline-summary-provides-guidance-to-screen-treat-and-manage-lupus-nephritis.

Rovin B.H., Teng Y.K.O., Ginzler E.M., Arriens C., Caster D.J., Romero-Diaz J., Gibson K., Kaplan J., Lisk L., Navarra S., et al. Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): A double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2021;397:2070–2080. doi: 10.1016/S0140-6736(21)00578-X. PubMed DOI

Rojas-Rivera J.E., Ortiz A., Fervenza F.C. Novel Treatments Paradigms: Membranous Nephropathy. Kidney Int. Rep. 2023;8:419–431. doi: 10.1016/j.ekir.2022.12.011. PubMed DOI PMC

Zonozi R., Laliberte K., Huizenga N.R., Rosenthal J.K., Jeyabalan A., Collins A.B., Cortazar F.B., Niles J.L. Combination of Rituximab, Low-Dose Cyclophosphamide, and Prednisone for Primary Membranous Nephropathy: A Case Series With Extended Follow Up. Am. J. Kidney Dis. 2021;78:793–803. doi: 10.1053/j.ajkd.2021.04.014. PubMed DOI

Dahan K., Debiec H., Plaisier E., Cachanado M., Rousseau A., Wakselman L., Michel P.-A., Mihout F., Dussol B., Matignon M., et al. Rituximab for severe membranous nephropathy: A 6-month trial with extended follow-up. J. Am. Soc. Nephrol. 2017;28:348–358. doi: 10.1681/ASN.2016040449. PubMed DOI PMC

GemaFernández-Juárez G., Rojas-Rivera J., van de Logt A.-E., Justino J., Sevillano A., Caravaca-Fontán F., Ávila A., Rabasco C., Cabello V., Varela A., et al. The STARMEN trial indicates that alternating treatment with corticosteroids and cyclophosphamide is superior to sequential treatment with tacrolimus and rituximab in primary membranous nephropathy. Kidney Int. 2021;99:986–998. doi: 10.1016/j.kint.2020.10.014. PubMed DOI

Sethi S., Kumar S., Lim K., Jordan S.C. Obinutuzumab is Effective for the Treatment of Refractory Membranous Nephropathy. Kidney Int. Rep. 2020;5:1515–1518. doi: 10.1016/j.ekir.2020.06.030. PubMed DOI PMC

Vink C.H., Wetzels J.F.M., Logt A.V. Combination Therapy With Rituximab and Low-Dose Cyclophosphamide and Prednisone in Membranous Nephropathy. Kidney Int. Rep. 2024;9:3439–3445. doi: 10.1016/j.ekir.2024.08.033. PubMed DOI PMC

Kochoyan Z., Dobronravov V.A. A novel approach to induce early remission in high-risk primary membranous nephropathy. Nephrol. Dial. Transplant. 2025;40:60–70. doi: 10.1093/ndt/gfae138. PubMed DOI

van de Logt A.-E., Wetzels J.F.M. Treatment of membranous nephropathy: A novel approach? Nephrol. Dial. Transplant. 2025;40:4–6. doi: 10.1093/ndt/gfae153. PubMed DOI

Cortazar F.B., Muhsin S.A., Pendergraft W.F., 3rd, Wallace Z.S., Dunbar C., Laliberte K., Niles J.L. Combination Therapy with Rituximab and Cyclophosphamide for Remission Induction in ANCA Vasculitis. Kidney Int. Rep. 2017;3:394–402. doi: 10.1016/j.ekir.2017.11.004. PubMed DOI PMC

Floege J., Jayne D.R., Sanders JS F., Tesar V., Rovin B.H. Kidney Disease: Improving Global Outcomes (KDIGO) ANCA Vasculitis Work Group. KDIGO 2024 Clinical Practice Guideline for the Management of Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis. Kidney Int. 2024;105:S71–S116. doi: 10.1016/j.kint.2023.10.008. Erratum in Kidney Int. 2024, 106, 160–163. PubMed DOI

Jayne D.R., Merkel P.A., Schall T.J., Bekker P. Avacopan for the treatment of ANCA-associated vasculitis. N. Engl. J. Med. 2021;384:599–609. doi: 10.1056/NEJMoa2023386. PubMed DOI

[(accessed on 6 January 2025)]. Available online: https://www.asn-online.org/education/kidneyweek/2024/program-abstract.aspx?controlId=4117726.

Zonozi R., Aqeel F., Le D., Cortazar F.B., Thaker J., Zabala Ramirez M.J., Sattui Cortes S.E., Attieh R.M., Chung M., Bulbin D.H., et al. Real-World Experience with Avacopan in Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis. Kidney Int. Rep. 2024;9:1783–1791. doi: 10.1016/j.ekir.2024.03.022. PubMed DOI PMC

Coppo R. Steps forward in the treatment of IgA nephropathy. Nat. Rev. Nephrol. 2024 doi: 10.1038/s41581-024-00925-y. PubMed DOI

Cheung C.K., Barratt J., Liew A., Zhang H., Tesar V., Lafayette R. The role of BAFF and APRIL in IgA nephropathy: Pathogenic mechanisms and targeted therapies. Front. Nephrol. 2024;3:1346769. doi: 10.3389/fneph.2023.1346769. PubMed DOI PMC

Lafayette R., Barbour S., Israni R., Wei X., Eren N., Floege J., Jha V., Kim S.G., Maes B., Phoon R.K.S., et al. A phase 2b, randomized, double-blind, placebo-controlled, clinical trial of atacicept for treatment of IgA nephropathy. Kidney Int. 2024;105:1306–1315. doi: 10.1016/j.kint.2024.03.012. PubMed DOI

Barratt J., Barbour S.J., Brenner R.M., Cooper K., Wei X., Eren N., Floege J., Jha V., Kim S.G., Maes B., et al. Long-term results from an open-label extension study of atacicept for the treatment of IgA nephropathy. J. Am. Soc. Nephrol. 2024 doi: 10.1681/ASN.0000000541. PubMed DOI PMC

Watts A.J.B., Keller K.H., Lerner G., Rosales I., Collins A.B., Sekulic M., Waikar S.S., Chandraker A., Riella L.V., Alexander M.P., et al. Discovery of Autoantibodies Targeting Nephrin in Minimal Change Disease Supports a Novel Autoimmune Etiology. J. Am. Soc. Nephrol. 2022;33:238–252. doi: 10.1681/ASN.2021060794. PubMed DOI PMC

Hengel F.E., Dehde S., Lassé M., Zahner G., Seifert L., Schnarre A., Kretz O., Demir F., Pinnschmidt H.O., Grahammer F., et al. International Society of Glomerular Disease. Autoantibodies Targeting Nephrin in Podocytopathies. N. Engl. J. Med. 2024;391:422–433. doi: 10.1056/NEJMoa2314471. PubMed DOI

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