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利妥昔单抗治疗特发性膜性肾病的研究进展
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Abstract:
特发性膜性肾病(idiopathic membranous nephropathy, IMN)，是一种病因未明的、由自身抗体介导的原发性肾小球肾炎，是构成原发性肾病综合征(nephrotic syndrome, NS)的常见病理类型之一。IMN治疗上主要包括非免疫抑制治疗和免疫抑制治疗，但随着对其发病机制的不断深入研究，B细胞在其中发挥重大作用。利妥昔单抗(RTX)，是一种小型嵌合鼠/人单克隆免疫抗体，通过作用于靶向B淋巴细胞上的CD20表面抗原，选择性地耗尽这些细胞，但RTX治疗IMN的效果是否优于传统免疫抑制剂尚存在争议，且RTX不同剂量在IMN中的应用目前尚未明确。本文就IMN的发病机制、治疗及RTX与其他免疫抑制剂对比及不同剂量用药治疗IMN的方案做一综述。
Idiopathic membranous nephropathy is a primary glomerulonephritis mediated by autoantibodies of unknown etiology, which is one of the common pathological types of primary nephrotic syndrome. The treatment of IMN mainly includes non-immunosuppressive therapy and immunosuppressive therapy, but with the continuous in-depth study of its pathogenesis, B cells play an important role in it. Rituximab, a small chimeric mouse/human monoclonal antibody, selectively depleted B lym-phocytes by targeting the CD20 surface antigen on these cells. However, the efficacy of RTX over conventional immunosuppressants in the treatment of IMN is controversial, and the application of different doses of RTX to IMN is not yet clear. This article reviews the pathogenesis and treatment of IMN, the comparison between RTX and other immunosuppressants, and the treatment of IMN with different doses.
| [1] | Hayashi, N., Okada, K., Matsui, Y., et al. (2018) Glomerular Mannose-Binding Lectin Deposition in Intrinsic Anti-gen-Related Membranous Nephropathy. Nephrology Dialysis Transplantation, 33, 832-840.
https://doi.org/10.1093/ndt/gfx235 |
| [2] | Dahan, K., Debiec, H., Plaisier, E., et al. (2017) Rituximab for Severe Membranous Nephropathy: A 6-Month Trial with Extended Follow-up. Journal of the American Society of Nephrology, 28, 348-358.
https://doi.org/10.1681/ASN.2016040449 |
| [3] | Luo, W., Olaru, F., Miner, J.H., et al. (2018) Alternative Pathway Is Essential for Glomerular Complement Activation and Proteinuria in a Mouse Model of Membranous Nephropathy. Frontiers in Immunology, 9, Article 1433.
https://doi.org/10.3389/fimmu.2018.01433 |
| [4] | Zhang, M.-F., Huang, J., Zhang, Y.-M., et al. (2019) Complement Activation Products in the Circulation and Urine of Primary Membranous Nephropathy. BMC Nephrology, 20, Article 313. https://doi.org/10.1186/s12882-019-1509-5 |
| [5] | Nangaku, M., Shankland, S.J. and Couser, W.G. (2005) Cellular Response to Injury in Membranous Nephropathy. Journal of the American Society of Nephrology, 16, 1195-1204. https://doi.org/10.1681/ASN.2004121098 |
| [6] | Beck Jr., L.H., Bonegio, R.G., Lambeau, G., et al. (2009) M-Type Phospholipase A2 Receptor as Target Antigen in Idiopathic Membranous Nephropathy. New England Journal of Medicine, 361, 11-21.
https://doi.org/10.1056/NEJMoa0810457 |
| [7] | Pan, Y., Wan, J., Liu, Y., et al. (2014) SPLA2 IB Induces Human Podocyte Apoptosis via the M-Type Phospholipase A2 Receptor. Scientific Reports, 4, Article No. 6660. https://doi.org/10.1038/srep06660 |
| [8] | Maifata, S.M., Hod, R., Zakaria, F. and Ghani, F.A. (2020) Role of Serum and Urine Biomarkers (PLA2R and THSD7A) in Diagnosis, Monitoring and Prognostication of Primary Membranous Glomerulonephritis. Biomolecules, 10, Article No. 319. https://doi.org/10.3390/biom10020319 |
| [9] | Kao, L., Lam, V., Waldman, M., Glassock, R.J. and Zhu, Q. (2015) Identification of the Immunodominant Epitope Region in Phospho-lipase A2 Receptor-Mediating Autoantibody Binding in Idiopathic Membranous Nephropathy. Journal of the American Society of Nephrology, 26, 291-301. https://doi.org/10.1681/ASN.2013121315 |
| [10] | Fresquet, M., Jowitt, T.A., Gummadova, J., et al. (2015) Identification of a Major Epitope Recognized by PLA2R Autoantibodies in Primary Mem-branous Nephropathy. Journal of the American Society of Nephrology, 26, 302-313.
https://doi.org/10.1681/ASN.2014050502 |
| [11] | Seitz-Polski, B., Dolla, G., Payré, C., et al. (2016) Epitope Spread-ing of Autoantibody Response to PLA2R Associates with Poor Prognosis in Membranous Nephropathy. Journal of the American Society of Nephrology, 27, 1517-1533.
https://doi.org/10.1681/ASN.2014111061 |
| [12] | Seitz-Polski, B., Debiec, H., Rousseau, A., et al. (2018) Phospho-lipase A2 Receptor 1 Epitope Spreading at Baseline Predicts Reduced Likelihood of Remission of Membranous Nephropathy. Journal of the American Society of Nephrology, 29, 401-408. https://doi.org/10.1681/ASN.2017070734 |
| [13] | Tomas, N.M., Beck Jr., L.H., Meyer-Schwesinger, C., et al. (2014) Thrombospondin Type-1 Domain-Containing 7A in Idiopathic Membranous Nephropathy. New England Journal of Medicine, 371, 2277-2287.
https://doi.org/10.1056/NEJMoa1409354 |
| [14] | Zaghrini, C., Seitz-Polski, B., Justino, J., et al. (2019) Novel ELISA for Thrombospondin Type 1 Domain-Containing 7A Autoantibodies in Membranous Nephropathy. Kidney International, 95, 666-679.
https://doi.org/10.1016/j.kint.2018.10.024 |
| [15] | Weinmann-Menke, J., Holtz, S., Sollinger, D., et al. (2019) Treat-ment of Membranous Nephropathy in Patients with THSD7A Antibodies Using Immunoadsorption. American Journal of Kidney Diseases, 74, 849-852.
https://doi.org/10.1053/j.ajkd.2019.05.021 |
| [16] | Hoxha, E., Beck Jr., L.H., Wiech, T., et al. (2017) An Indirect Im-munofluorescence Method Facilitates Detection of Thrombospondin Type 1 Domain-Containing 7A-Specific Antibodies in Membranous Nephropathy. Journal of the American Society of Nephrology, 28, 520-531. https://doi.org/10.1681/ASN.2016010050 |
| [17] | Gu, Y., Xu, H. and Tang, D. (2021) Mechanisms of Primary Membranous Nephropathy. Biomolecules, 11, Article No. 513. https://doi.org/10.3390/biom11040513 |
| [18] | Caza, T.N., Hassen, S.I., Kuperman, M., et al. (2021) Neural Cell Adhesion Molecule 1 Is A Novel Autoantigen in Membra-nous Lupus Nephritis. Kidney International, 100, 171-181. https://doi.org/10.1016/j.kint.2020.09.016 |
| [19] | van de Logt, A.E., Fresquet, M., Wetzels, J.F. and Brenchley, P. (2019) The Anti-PLA2R Antibody in Membranous Nephrop-athy: What We Know and What Remains a Decade After Its Discovery. Kidney International, 96, 1292-1302.
https://doi.org/10.1016/j.kint.2019.07.014 |
| [20] | 栾如梅, 郑倩, 慈鑫, 卢雪红. 吸烟对特发性膜性肾病患者肾功能及病理变化的影响[J]. 临床肾脏病杂志, 2020, 20(3): 198-202. |
| [21] | Xu, X., Wang, G., Chen, N., et al. (2016) Long-Term Exposure to Air Pollution and Increased Risk of Membranous Nephropathy in China. Journal of the Ameri-can Society of Nephrology, 27, 3739-3746.
https://doi.org/10.1681/ASN.2016010093 |
| [22] | Liu, W., Gao, C., Dai, H., et al. (2019) Immunological Pathogene-sis of Membranous Nephropathy: Focus on PLA2R1 and Its Role. Frontiers in Immunology, 10, Article 1809. https://doi.org/10.3389/fimmu.2019.01809 |
| [23] | 王涛, 李婷婷, 杨洪娟. 利妥昔单抗治疗特发性膜性肾病的研究进展[J]. 中华肾病研究电子杂志, 2017, 6(5): 228-232. |
| [24] | Rovin, B.H., Adler, S.G., Barratt, J., et al. (2021) Ex-ecutive Summary of the KDIGO 2021 Guideline for the Management of Glomerular Diseases. Kidney International, 100, 753-779. https://doi.org/10.1016/j.kint.2021.05.015 |
| [25] | Salles, G., Barrett, M., Foà, R., et al. (2017) Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience. Advances in Therapy, 34, 2232-2273. https://doi.org/10.1007/s12325-017-0612-x |
| [26] | 陈楠. 生物制剂在肾脏疾病中的应用进展[J]. 现代实用医学, 2020, 32(12): 1446-1448. |
| [27] | Scolari, F., Delbarba, E., Santoro, D., et al. (2021) Rituximab or Cyclophosphamide in the Treatment of Membranous Nephropathy: The RI-CYCLO Randomized Trial. Journal of the American Society of Nephrology, 32, 972-982.
https://doi.org/10.1681/ASN.2020071091 |
| [28] | Fernández-Juárez, G., Rojas-Rivera, J., van de Logt, A.-E., et al. (2021) The STARMEN Trial Indicates That Alternating Treatment with Corticosteroids and Cyclophosphamide Is Supe-rior to Sequential Treatment with Tacrolimus and Rituximab in Primary Membranous Nephropathy. Kidney International, 99, 986-998.
https://doi.org/10.1016/j.kint.2020.10.014 |
| [29] | 刘纯玲, 王述蔷, 耿晓东, 等. 利妥昔单抗或他克莫司联合糖皮质激素治疗特发性膜性肾病的疗效比较[J]. 临床肾脏病杂志, 2019, 19(6): 421-425. |
| [30] | Fervenza, F.C., Appel, G.B., Barbour, S.J., et al. (2019) Rituximab or Cyclosporine in the Treatment of Membranous Nephropathy. New Eng-land Journal of Medicine, 381, 36-46. https://doi.org/10.1056/NEJMoa1814427 |
| [31] | Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group (2021) KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney International, 100, S1-S276.
https://doi.org/10.1016/j.kint.2021.05.021 |
| [32] | Ruggenenti, P., Cravedi, P., Chianca, A., et al. (2012) Rituximab in Idiopathic Membranous Nephropathy. Journal of the American Society of Nephrology, 23, 1416-1425. https://doi.org/10.1681/ASN.2012020181 |
| [33] | 袁仲飞, 刘先燕, 何剑. 低剂量利妥昔单抗治疗难治性特发性膜性肾病的临床疗效分析[J]. 临床肾脏病杂志, 2021, 21(3): 215-219. |
| [34] | 徐潇漪, 王国勤, 程虹, 等. 小剂量利妥昔单抗治疗特发性膜性肾病的疗效及其影响因素[J]. 首都医科大学学报, 2022, 43(5): 680-686. |
| [35] | Seitz-Polski, B., Dahan, K., Debiec, H., et al. (2019) High-Dose Rituximab and Early Remission in PLA2R1-Related Membranous Nephropathy. Clinical Journal of the American Society of Nephrology, 14, 1173-1182.
https://doi.org/10.2215/CJN.11791018 |
| [36] | Moroni, G., Depetri, F., Del Vecchio, L., et al. (2017) Low-Dose Rituximab Is Poorly Effective in Patients with Primary Membranous Nephropathy. Nephrology Dialysis Transplantation, 32, 1691-1696.
https://doi.org/10.1093/ndt/gfw251 |
| [37] | Cravedi, P. (2017) Rituximab in Membranous Nephropathy: Not All Studies Are Created Equal. Nephron, 135, 46-50.
https://doi.org/10.1159/000450659 |
| [38] | Klomjit, N., Fervenza, F.C. and Zand, L. (2020) Successful Treatment of Patients with Refractory PLA2R-Associated Membranous Nephropathy with Obinutuzumab: A Report of 3 Cases. American Journal of Kidney Diseases, 76, 883-888.
https://doi.org/10.1053/j.ajkd.2020.02.444 |
| [39] | Sethi, S., Kumar, S., Lim, K. and Jordan, S.C. (2020) Obinutuzumab Is Effective for the Treatment of Refractory Membranous Nephropathy. Kidney International Reports, 5, 1515-1518. https://doi.org/10.1016/j.ekir.2020.06.030 |
| [40] | Boyer-Suavet, S., Andreani, M., Lateb, M., et al. (2019) Neutralizing Anti-Rituximab Antibodies and Relapse in Membranous Nephropathy Treated with Rituximab. Frontiers in Immunology, 10, Article 3069.
https://doi.org/10.3389/fimmu.2019.03069 |
| [41] | Ronco, P., Beck, L., Debiec, H., et al. (2021) Membranous Nephropathy. Nature Reviews Disease Primers, 7, Article No. 69. https://doi.org/10.1038/s41572-021-00303-z |
| [42] | Jefferson, J.A. (2018) Complications of Immunosuppression in Glomerular Disease. Clinical Journal of the American Society of Nephrology, 13, 1264-1275. https://doi.org/10.2215/CJN.01920218 |
| [43] | Focosi, D., Tuccori, M. and Maggi, F. (2019) Progressive Multifocal Leukoencephalopathy and Anti-CD20 Monoclonal Antibodies: What Do We Know after 20 Years of Rituximab. Reviews in Medical Virology, 29, e2077.
https://doi.org/10.1002/rmv.2077 |
| [44] | European Association for the Study of the Liver (2012) EASL Clinical Prac-tice Guidelines: Management of Chronic Hepatitis B Virus Infection. Journal of Hepatology, 57, 167-185. https://doi.org/10.1016/j.jhep.2012.02.010 |
| [45] | Liaw, Y.-F., Kao, J.-H., Piratvisuth, T., et al. (2012) Asian-Pacific Consensus Statement on the Management of Chronic Hepatitis B: A 2012 Update. Hepatology International, 6, 531-561. https://doi.org/10.1007/s12072-012-9365-4 |
| [46] | Alkadi, A., Alduaiji, N. and Alrehaily, A. (2017) Risk of Tuber-culosis Reactivation with Rituximab Therapy. International Journal of Health Sciences, 11, 41-44. |
| [47] | Sohal, R., Sohal, S., Wazir, A. and Lee, M. (2020) Rituximab-Associated Reactivation of Tuberculosis. American Journal of Therapeutics, 29, e113-e115. https://doi.org/10.1097/MJT.0000000000001257 |
| [48] | Podestà, M.A., Ruggiero, B., Remuzzi, G., Remuzzi, G. and Ruggenenti, P. (2020) Ofatumumab for Multirelapsing Membranous Nephropathy Complicated by Rituximab-Induced Serum-Sickness. BMJ Case Reports, 13, e232896.
https://doi.org/10.1136/bcr-2019-232896 |
