Update on the treatment of primary membranous glomerulonephritis
Article Sidebar
Publicación 7. Vol 6. Num 3.2 (Español (España))
HTML (Español (España))
EPUB (Español (España))
FLIP (Español (España))
Published:
Sep 27, 2023
Keywords:
Diagnosis, Risk Factors, Membranous Glomerulonephritis, Therapeutics.
Main Article Content
Abstract
Introduction: Membranous nephropathy (MN) represents a glomerular disorder characterized by thickening of capillary walls due to immune complexes. This condition prevails as the primary cause of nephrotic syndrome in non-diabetic adults over 40 years old, although it also affects children less frequently. The estimated incidence varies geographically but remains constrained by the lack of representative studies. Although largely autoimmune and associated with anti-PLA2R antibodies, treatment addresses new therapies and emerging antibody discoveries. Methodology: A literature review will be conducted to gather and analyze relevant studies on the treatment of primary membranous glomerulonephritis, using specific inclusion criteria. Irrelevant articles were excluded, and the search encompassed databases such as PubMed, Web of Science, and ProQuest, employing search terms and Boolean operators. Discussion: Various studies on the treatment of primary membranous glomerulonephritis reveal diverse approaches. Cyclophosphamide expedited recovery in one study, while prednisone and rituximab yielded limited results. The amount of proteinuria proved critical in preserving renal function. Immunosuppressive therapy generally outperformed non-immunosuppressive approaches. Detection of high anti-PLA2R antibody levels indicated poor response to tacrolimus. Thyroid dysfunction and rituximab influenced outcomes. Antibody-guided therapy demonstrated high remission rates. Prophylactic aspirin or warfarin may benefit patients with low serum albumin. Conclusion: The treatment of idiopathic membranous nephropathy is complex. Rituximab and antibody-guided therapy are effective, but the choice depends on factors such as age, antibodies, thyroid function, and others. A personalized approach is needed to enhance remission and patients' quality of life.
Downloads
Download data is not yet available.
Article Details
How to Cite
Pozo Guzmán, L. C., & Bueno Castro, A. S. (2023). Update on the treatment of primary membranous glomerulonephritis . ConcienciaDigital, 6(3.2), 146-170. https://doi.org/10.33262/concienciadigital.v6i3.2.2690
Section
Artículos
References
Akiyama, S., Imai, E., & Maruyama, S. (2019). Immunology of membranous nephropathy [version 1; peer review: 3 approved]. F1000Research, 8(May), 1–9. https://doi.org/10.12688/f1000research.17589.1
Alsharhan, L., & Beck, L. H. (2021). Membranous Nephropathy: Core Curriculum 2021. American Journal of Kidney Diseases, 77(3), 440–453. https://doi.org/10.1053/j.ajkd.2020.10.009
Bose, B., Chung, E. Y. M., Hong, R., Strippoli, G. F. M., Johnson, D. W., Yang, W. ling, Badve, S. V., & Palmer, S. C. (2022). Immunosuppression therapy for idiopathic membranous nephropathy: systematic review with network meta-analysis. Journal of Nephrology, 35(4), 1159–1170. https://doi.org/10.1007/s40620-022-01268-2
Chen, S. Y., Chen, C. H., Huang, Y. C., Chan, C. J., Hsieh, Y. Y., Yu, M. C., Tsai, C. H., & Tsai, F. J. (2011). Association of STAT4 polymorphisms with susceptibility to primary membranous glomerulonephritis and renal failure. Clinica Chimica Acta, 412(21–22), 1899–1904. https://doi.org/10.1016/j.cca.2011.06.020
Chung, E. Y. M., Wang, Y. M., Keung, K., Hu, M., McCarthy, H., Wong, G., Kairaitis, L., Bose, B., Harris, D. C. H., & Alexander, S. I. (2022). Membranous nephropathy: Clearer pathology and mechanisms identify potential strategies for treatment. Frontiers in Immunology, 13(November), 1–20. https://doi.org/10.3389/fimmu.2022.1036249
Dai, P., Campbell, D., Culican, S., Brown, D. A., Byth, K., Hissaria, P., Ninnes, R., Nankivell, B., & Lin, M. W. (2020). Validation of phospholipase A2 receptor direct immunofluorescence staining in the diagnosis of primary membranous glomerulonephritis. Pathology, 52(5), 546–551. https://doi.org/10.1016/j.pathol.2020.04.003
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., Simon, J. F., McCarthy, E. T., Brenchley, P., Sethi, S., Avila-Casado, C., Beanlands, H., Lieske, J. C., Philibert, D., Li, T., … Cattran, D. C. (2019). Rituximab or Cyclosporine in the Treatment of Membranous Nephropathy. New England Journal of Medicine, 381(1), 36–46. https://doi.org/10.1056/nejmoa1814427
Gao, S., Cui, Z., Wang, X., Zhang, Y. M., Wang, F., Cheng, X. Y., Meng, L. Q., Zhou, F. De, Liu, G., & Zhao, M. H. (2021). Rituximab Therapy for Primary Membranous Nephropathy in a Chinese Cohort. Frontiers in Medicine, 8(May). https://doi.org/10.3389/fmed.2021.663680
Gao, S., Cui, Z., & Zhao, M. H. (2022). Complement C3a and C3a Receptor Activation Mediates Podocyte Injuries in the Mechanism of Primary Membranous Nephropathy. Journal of the American Society of Nephrology, 33(9), 1742–1756. https://doi.org/10.1681/ASN.2021101384
Gu, Q. hua, Cao, X., Mao, X. ming, Jia, J. ya, & Yan, T. kun. (2022). Significance of thyroid dysfunction in the patients with primary membranous nephropathy. BMC Nephrology, 23(1), 1–11. https://doi.org/10.1186/s12882-022-03023-y
Hemanth Kumar, M. K., Sandhu, J., & Sandhu, J. S. (2022). Profile and primary treatment outcomes in membranous nephropathy. Saudi Medical Journal, 43(9), 1051–1056. https://doi.org/10.15537/smj.2022.43.9.20220459
Keri, K. C., Blumenthal, S., Kulkarni, V., Beck, L., & Chongkrairatanakul, T. (2019). Primary membranous nephropathy: Comprehensive review and historical perspective. Postgraduate Medical Journal, 95(1119), 23–31. https://doi.org/10.1136/postgradmedj-2018-135729
Kim, Y., Yoon, H. E., Chung, B. H., Choi, B. S., Park, C. W., Yang, C. W., Kim, Y. S., Hong, Y. A., Kim, S. Y., Chang, Y. K., & Hwang, H. S. (2019). Clinical outcomes and effects of treatment in older patients with idiopathic membranous nephropathy. Korean Journal of Internal Medicine, 34(5), 1091–1099. https://doi.org/10.3904/kjim.2018.139
Lerner, G. B., Virmani, S., Henderson, J. M., Francis, J. M., & Beck, L. H. (2021). A conceptual framework linking immunology, pathology, and clinical features in primary membranous nephropathy. Kidney International, 100(2), 289–300. https://doi.org/10.1016/j.kint.2021.03.028
Maifata, S. M., Hod, R., Zakaria, F., & Ghani, F. A. (2020). Role of serum and urine biomarkers (PLA2R and THSD7A) in diagnosis, monitoring and prognostication of primary membranous glomerulonephritis. Biomolecules, 10(2). https://doi.org/10.3390/biom10020319
Matsuzaki, T., Watanabe, Y., Tanaka, A., Furuhashi, K., Saito, S., & Maruyama, S. (2023). Prognosis and incidence of infections in chronic kidney disease patients with membranous nephropathy enrolled in a large Japanese clinical claims database. BMC Nephrology, 24(1), 1–11. https://doi.org/10.1186/s12882-023-03190-6
Nafar, M., Dalili, N., & Samavat, S. (2020). Biomarkers in primary membranous nephropathy, a guide to precision medicine. Iranian Journal of Kidney Diseases, 14(5), 335–347.
Rojas-Rivera, J. E., & Ortiz Arduán, A. (2021). Nefropatía membranosa primaria en la era de los autoanticuerpos y de las terapias biológicas. Medicina Clínica, 157(3), 121–129. https://doi.org/10.1016/j.medcli.2021.02.010
Rojas-Rivera, J., Fervenza, F. C., & Ortiz, A. (2022). Recent Clinical Trials Insights into the Treatment of Primary Membranous Nephropathy. Drugs, 82(2), 109–132. https://doi.org/10.1007/s40265-021-01656-1
Ronco, P., Beck, L., Debiec, H., Fervenza, F. C., Hou, F. F., Jha, V., Sethi, S., Tong, A., Vivarelli, M., & Wetzels, J. (2021). Membranous nephropathy. Nature Reviews Disease Primers, 7(1). https://doi.org/10.1038/s41572-021-00303-z
Ronco, P., & Debiec, H. (2021). Membranous nephropathy: Current understanding of various causes in light of new target antigens. Current Opinion in Nephrology and Hypertension, 30(3), 287–293. https://doi.org/10.1097/MNH.0000000000000697
Safar-Boueri, L., Piya, A., Beck, L. H., & Ayalon, R. (2021). Membranous nephropathy: diagnosis, treatment, and monitoring in the post-PLA2R era. Pediatric Nephrology, 36(1), 19–30. https://doi.org/10.1007/s00467-019-04425-1
Salant, D. J. (2018). Unmet Challenges in Membranous Nephropathy. Physiology & Behavior, 176(5), 139–148. https://doi.org/10.4049/jimmunol.1801473.The
Scolari, F., Alberici, F., Mescia, F., Delbarba, E., Trujillo, H., Praga, M., & Ponticelli, C. (2022). Therapies for Membranous Nephropathy: A Tale From the Old and New Millennia. Frontiers in Immunology, 13(March). https://doi.org/10.3389/fimmu.2022.789713
Scolari, F., Delbarba, E., Santoro, D., Gesualdo, L., Pani, A., Dallera, N., Mani, L. Y., Santostefano, M., Feriozzi, S., Quaglia, M., Boscutti, G., Ferrantelli, A., Marcantoni, C., Passerini, P., Magistroni, R., Alberici, F., Ghiggeri, G. M., Ponticelli, C., & Ravani, P. (2021). Rituximab or Cyclophosphamide in the Treatment of Membranous Nephropathy: The RI-CYCLO Randomized Trial. Journal of the American Society of Nephrology, 32(4), 972–982. https://doi.org/10.1681/ASN.2020071091
Stahl, R. A. K., Reinhard, L., & Hoxha, E. (2019). Characterization of autoantibodies in primary membranous nephropathy and their clinical significance. Expert Review of Clinical Immunology, 15(2), 165–175. https://doi.org/10.1080/1744666X.2019.1548934
Starzyńska-Kubicka, A., Perkowska-Ptasińska, A., & Górnicka, B. (2018). Membranous glomerulonephritis – A common,unspecific pattern of glomerular injury. Polish Journal of Pathology, 69(3), 209–218. https://doi.org/10.5114/pjp.2018.79540
Tesar, V., & Hruskova, Z. (2021). Autoantibodies in the Diagnosis, Monitoring, and Treatment of Membranous Nephropathy. Frontiers in Immunology, 12(March), 1–10. https://doi.org/10.3389/fimmu.2021.593288
van de Logt, A. E., Fresquet, M., Wetzels, J. F., & Brenchley, P. (2019). The anti-PLA2R antibody in membranous nephropathy: what we know and what remains a decade after its discovery. Kidney International, 96(6), 1292–1302. https://doi.org/10.1016/j.kint.2019.07.014
Vink, C. H., Logt, A. E. van de, van der Molen, R. G., Hofstra, J. M., & Wetzels, J. F. M. (2023). Antibody-Guided Therapy in Phospholipase A2 Receptor-Associated Membranous Nephropathy. Kidney International Reports, 8(3), 432–441. https://doi.org/10.1016/j.ekir.2022.12.003
Wang, B., Zhu, Z., Huang, F., Huang, H., Tu, L., Wang, Y., Zheng, L., Zhou, J., & Wei, X. (2022). Anti-phospholipase A2 receptor antibody levels at diagnosis predicts outcome of TAC-based treatment for idiopathic membranous nephropathy patients. BMC Nephrology, 23(1), 1–10. https://doi.org/10.1186/s12882-022-02914-4
Westermann, L., Rottmann, F. A., Hug, M. J., Staudacher, D. L., Wobser, R., Arnold, F., & Welte, T. (2023). Clinical covariates influencing clinical outcomes in primary membranous nephropathy. BMC Nephrology, 24(1), 235. https://doi.org/10.1186/s12882-023-03288-x
Yamaguchi, M., Ando, M., Katsuno, T., Tsuboi, N., & Maruyama, S. (2018). Urinary protein and renal prognosis in idiopathic membranous nephropathy: a multicenter retrospective cohort study in Japan. Renal Failure, 40(1), 435–441. https://doi.org/10.1080/0886022X.2018.1487864
Zhang, J., Bian, L., Ma, F. Z., Jia, Y., & Lin, P. (2018). Efficacy and safety of rituximab therapy for membranous nephropathy: A meta-analysis. European Review for Medical and Pharmacological Sciences, 22(22), 8021–8029. https://doi.org/10.26355/eurrev-201811-16431
Zou, H., Li, Y., & Xu, G. (2019). Management of anticoagulation and antiplatelet therapy in patients with primary membranous nephropathy. BMC Nephrology, 20(1), 1–12. https://doi.org/10.1186/s12882-019-1637-y
Alsharhan, L., & Beck, L. H. (2021). Membranous Nephropathy: Core Curriculum 2021. American Journal of Kidney Diseases, 77(3), 440–453. https://doi.org/10.1053/j.ajkd.2020.10.009
Bose, B., Chung, E. Y. M., Hong, R., Strippoli, G. F. M., Johnson, D. W., Yang, W. ling, Badve, S. V., & Palmer, S. C. (2022). Immunosuppression therapy for idiopathic membranous nephropathy: systematic review with network meta-analysis. Journal of Nephrology, 35(4), 1159–1170. https://doi.org/10.1007/s40620-022-01268-2
Chen, S. Y., Chen, C. H., Huang, Y. C., Chan, C. J., Hsieh, Y. Y., Yu, M. C., Tsai, C. H., & Tsai, F. J. (2011). Association of STAT4 polymorphisms with susceptibility to primary membranous glomerulonephritis and renal failure. Clinica Chimica Acta, 412(21–22), 1899–1904. https://doi.org/10.1016/j.cca.2011.06.020
Chung, E. Y. M., Wang, Y. M., Keung, K., Hu, M., McCarthy, H., Wong, G., Kairaitis, L., Bose, B., Harris, D. C. H., & Alexander, S. I. (2022). Membranous nephropathy: Clearer pathology and mechanisms identify potential strategies for treatment. Frontiers in Immunology, 13(November), 1–20. https://doi.org/10.3389/fimmu.2022.1036249
Dai, P., Campbell, D., Culican, S., Brown, D. A., Byth, K., Hissaria, P., Ninnes, R., Nankivell, B., & Lin, M. W. (2020). Validation of phospholipase A2 receptor direct immunofluorescence staining in the diagnosis of primary membranous glomerulonephritis. Pathology, 52(5), 546–551. https://doi.org/10.1016/j.pathol.2020.04.003
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., Simon, J. F., McCarthy, E. T., Brenchley, P., Sethi, S., Avila-Casado, C., Beanlands, H., Lieske, J. C., Philibert, D., Li, T., … Cattran, D. C. (2019). Rituximab or Cyclosporine in the Treatment of Membranous Nephropathy. New England Journal of Medicine, 381(1), 36–46. https://doi.org/10.1056/nejmoa1814427
Gao, S., Cui, Z., Wang, X., Zhang, Y. M., Wang, F., Cheng, X. Y., Meng, L. Q., Zhou, F. De, Liu, G., & Zhao, M. H. (2021). Rituximab Therapy for Primary Membranous Nephropathy in a Chinese Cohort. Frontiers in Medicine, 8(May). https://doi.org/10.3389/fmed.2021.663680
Gao, S., Cui, Z., & Zhao, M. H. (2022). Complement C3a and C3a Receptor Activation Mediates Podocyte Injuries in the Mechanism of Primary Membranous Nephropathy. Journal of the American Society of Nephrology, 33(9), 1742–1756. https://doi.org/10.1681/ASN.2021101384
Gu, Q. hua, Cao, X., Mao, X. ming, Jia, J. ya, & Yan, T. kun. (2022). Significance of thyroid dysfunction in the patients with primary membranous nephropathy. BMC Nephrology, 23(1), 1–11. https://doi.org/10.1186/s12882-022-03023-y
Hemanth Kumar, M. K., Sandhu, J., & Sandhu, J. S. (2022). Profile and primary treatment outcomes in membranous nephropathy. Saudi Medical Journal, 43(9), 1051–1056. https://doi.org/10.15537/smj.2022.43.9.20220459
Keri, K. C., Blumenthal, S., Kulkarni, V., Beck, L., & Chongkrairatanakul, T. (2019). Primary membranous nephropathy: Comprehensive review and historical perspective. Postgraduate Medical Journal, 95(1119), 23–31. https://doi.org/10.1136/postgradmedj-2018-135729
Kim, Y., Yoon, H. E., Chung, B. H., Choi, B. S., Park, C. W., Yang, C. W., Kim, Y. S., Hong, Y. A., Kim, S. Y., Chang, Y. K., & Hwang, H. S. (2019). Clinical outcomes and effects of treatment in older patients with idiopathic membranous nephropathy. Korean Journal of Internal Medicine, 34(5), 1091–1099. https://doi.org/10.3904/kjim.2018.139
Lerner, G. B., Virmani, S., Henderson, J. M., Francis, J. M., & Beck, L. H. (2021). A conceptual framework linking immunology, pathology, and clinical features in primary membranous nephropathy. Kidney International, 100(2), 289–300. https://doi.org/10.1016/j.kint.2021.03.028
Maifata, S. M., Hod, R., Zakaria, F., & Ghani, F. A. (2020). Role of serum and urine biomarkers (PLA2R and THSD7A) in diagnosis, monitoring and prognostication of primary membranous glomerulonephritis. Biomolecules, 10(2). https://doi.org/10.3390/biom10020319
Matsuzaki, T., Watanabe, Y., Tanaka, A., Furuhashi, K., Saito, S., & Maruyama, S. (2023). Prognosis and incidence of infections in chronic kidney disease patients with membranous nephropathy enrolled in a large Japanese clinical claims database. BMC Nephrology, 24(1), 1–11. https://doi.org/10.1186/s12882-023-03190-6
Nafar, M., Dalili, N., & Samavat, S. (2020). Biomarkers in primary membranous nephropathy, a guide to precision medicine. Iranian Journal of Kidney Diseases, 14(5), 335–347.
Rojas-Rivera, J. E., & Ortiz Arduán, A. (2021). Nefropatía membranosa primaria en la era de los autoanticuerpos y de las terapias biológicas. Medicina Clínica, 157(3), 121–129. https://doi.org/10.1016/j.medcli.2021.02.010
Rojas-Rivera, J., Fervenza, F. C., & Ortiz, A. (2022). Recent Clinical Trials Insights into the Treatment of Primary Membranous Nephropathy. Drugs, 82(2), 109–132. https://doi.org/10.1007/s40265-021-01656-1
Ronco, P., Beck, L., Debiec, H., Fervenza, F. C., Hou, F. F., Jha, V., Sethi, S., Tong, A., Vivarelli, M., & Wetzels, J. (2021). Membranous nephropathy. Nature Reviews Disease Primers, 7(1). https://doi.org/10.1038/s41572-021-00303-z
Ronco, P., & Debiec, H. (2021). Membranous nephropathy: Current understanding of various causes in light of new target antigens. Current Opinion in Nephrology and Hypertension, 30(3), 287–293. https://doi.org/10.1097/MNH.0000000000000697
Safar-Boueri, L., Piya, A., Beck, L. H., & Ayalon, R. (2021). Membranous nephropathy: diagnosis, treatment, and monitoring in the post-PLA2R era. Pediatric Nephrology, 36(1), 19–30. https://doi.org/10.1007/s00467-019-04425-1
Salant, D. J. (2018). Unmet Challenges in Membranous Nephropathy. Physiology & Behavior, 176(5), 139–148. https://doi.org/10.4049/jimmunol.1801473.The
Scolari, F., Alberici, F., Mescia, F., Delbarba, E., Trujillo, H., Praga, M., & Ponticelli, C. (2022). Therapies for Membranous Nephropathy: A Tale From the Old and New Millennia. Frontiers in Immunology, 13(March). https://doi.org/10.3389/fimmu.2022.789713
Scolari, F., Delbarba, E., Santoro, D., Gesualdo, L., Pani, A., Dallera, N., Mani, L. Y., Santostefano, M., Feriozzi, S., Quaglia, M., Boscutti, G., Ferrantelli, A., Marcantoni, C., Passerini, P., Magistroni, R., Alberici, F., Ghiggeri, G. M., Ponticelli, C., & Ravani, P. (2021). Rituximab or Cyclophosphamide in the Treatment of Membranous Nephropathy: The RI-CYCLO Randomized Trial. Journal of the American Society of Nephrology, 32(4), 972–982. https://doi.org/10.1681/ASN.2020071091
Stahl, R. A. K., Reinhard, L., & Hoxha, E. (2019). Characterization of autoantibodies in primary membranous nephropathy and their clinical significance. Expert Review of Clinical Immunology, 15(2), 165–175. https://doi.org/10.1080/1744666X.2019.1548934
Starzyńska-Kubicka, A., Perkowska-Ptasińska, A., & Górnicka, B. (2018). Membranous glomerulonephritis – A common,unspecific pattern of glomerular injury. Polish Journal of Pathology, 69(3), 209–218. https://doi.org/10.5114/pjp.2018.79540
Tesar, V., & Hruskova, Z. (2021). Autoantibodies in the Diagnosis, Monitoring, and Treatment of Membranous Nephropathy. Frontiers in Immunology, 12(March), 1–10. https://doi.org/10.3389/fimmu.2021.593288
van de Logt, A. E., Fresquet, M., Wetzels, J. F., & Brenchley, P. (2019). The anti-PLA2R antibody in membranous nephropathy: what we know and what remains a decade after its discovery. Kidney International, 96(6), 1292–1302. https://doi.org/10.1016/j.kint.2019.07.014
Vink, C. H., Logt, A. E. van de, van der Molen, R. G., Hofstra, J. M., & Wetzels, J. F. M. (2023). Antibody-Guided Therapy in Phospholipase A2 Receptor-Associated Membranous Nephropathy. Kidney International Reports, 8(3), 432–441. https://doi.org/10.1016/j.ekir.2022.12.003
Wang, B., Zhu, Z., Huang, F., Huang, H., Tu, L., Wang, Y., Zheng, L., Zhou, J., & Wei, X. (2022). Anti-phospholipase A2 receptor antibody levels at diagnosis predicts outcome of TAC-based treatment for idiopathic membranous nephropathy patients. BMC Nephrology, 23(1), 1–10. https://doi.org/10.1186/s12882-022-02914-4
Westermann, L., Rottmann, F. A., Hug, M. J., Staudacher, D. L., Wobser, R., Arnold, F., & Welte, T. (2023). Clinical covariates influencing clinical outcomes in primary membranous nephropathy. BMC Nephrology, 24(1), 235. https://doi.org/10.1186/s12882-023-03288-x
Yamaguchi, M., Ando, M., Katsuno, T., Tsuboi, N., & Maruyama, S. (2018). Urinary protein and renal prognosis in idiopathic membranous nephropathy: a multicenter retrospective cohort study in Japan. Renal Failure, 40(1), 435–441. https://doi.org/10.1080/0886022X.2018.1487864
Zhang, J., Bian, L., Ma, F. Z., Jia, Y., & Lin, P. (2018). Efficacy and safety of rituximab therapy for membranous nephropathy: A meta-analysis. European Review for Medical and Pharmacological Sciences, 22(22), 8021–8029. https://doi.org/10.26355/eurrev-201811-16431
Zou, H., Li, Y., & Xu, G. (2019). Management of anticoagulation and antiplatelet therapy in patients with primary membranous nephropathy. BMC Nephrology, 20(1), 1–12. https://doi.org/10.1186/s12882-019-1637-y