Renal Division, Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
J Formos Med Assoc. 2024 Feb;123(2):149-158. doi: 10.1016/j.jfma.2023.06.020. Epub 2023 Jul 11.
Targeted therapy has emerged as a more precise approach to treat glomerular diseases, focusing on specific molecular or cellular processes that contribute to disease development or progression. This approach complements or replaces traditional immunosuppressive therapy, optimizes supportive care, and provides a more personalized treatment strategy. In this review, we summarize the evolving understanding of pathogenic mechanisms in immune-mediated glomerular diseases and the developing targeted therapies based on these mechanisms. We begin by discussing pan-B-cell depletion, anti-CD20 rituximab, and targeting B-cell survival signaling through the BAFF/APRIL pathway. We also exam specific plasma cell depletion with anti-CD38 antibody. We then shift our focus to complement activation in glomerular diseases, which is involved in antibody-mediated glomerular diseases, such as IgA nephropathy, membranous nephropathy, ANCA-associated vasculitis, and lupus nephritis. Non-antibody-mediated complement activation occurs in glomerular diseases, including C3 glomerulopathy, complement-mediated atypical hemolytic uremic syndrome, and focal segmental glomerulosclerosis. We discuss specific inhibition of terminal, lectin, and alternative pathways in different glomerular diseases. Finally, we summarize current clinical trials targeting the final pathways of various glomerular diseases, including kidney fibrosis. We conclude that targeted therapy based on individualized pathogenesis should be the future of treating glomerular diseases.
靶向治疗已成为治疗肾小球疾病的一种更精确的方法，其重点是针对导致疾病发展或进展的特定分子或细胞过程。这种方法补充或替代了传统的免疫抑制疗法，优化了支持性护理，并提供了更具个性化的治疗策略。在这篇综述中，我们总结了对免疫介导的肾小球疾病发病机制的不断发展的认识，以及基于这些机制的新兴靶向治疗方法。我们首先讨论了全 B 细胞耗竭、抗 CD20 利妥昔单抗以及通过 BAFF/APRIL 通路靶向 B 细胞存活信号。我们还检查了针对特定浆细胞的 CD38 抗体耗竭。然后，我们将注意力转移到肾小球疾病中的补体激活，该激活涉及抗体介导的肾小球疾病，如 IgA 肾病、膜性肾病、ANCA 相关性血管炎和狼疮性肾炎。非抗体介导的补体激活发生在肾小球疾病中，包括 C3 肾小球病、补体介导的非典型溶血性尿毒症综合征和局灶节段性肾小球硬化症。我们讨论了针对不同肾小球疾病中终末、凝集素和替代途径的特定抑制作用。最后，我们总结了目前针对各种肾小球疾病（包括肾脏纤维化）的终末途径的临床试验。我们的结论是，基于个体化发病机制的靶向治疗应该是治疗肾小球疾病的未来。
