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狼疮性肾炎的治疗:现有范式和新兴策略。

Treatment of lupus nephritis: current paradigms and emerging strategies.

机构信息

Division of Rheumatology, Russell/Engleman Research Center, University of California, San Francisco, California, USA.

出版信息

Curr Opin Rheumatol. 2017 May;29(3):241-247. doi: 10.1097/BOR.0000000000000381.

Abstract

PURPOSE OF REVIEW

Lupus nephritis is the most common organ-threatening manifestation of lupus and continues to result in end-stage renal disease. This review describes the contemporary treatment of lupus nephritis as well as emerging therapeutic strategies.

RECENT FINDINGS

Lupus nephritis management consists of an initial (induction) phase and a maintenance (extended) phase in which steroids are used in combination with another immunosuppressive medication. Current treatments are incompletely effective and associated with substantial toxicity. Despite disappointing results of several recent trials, novel therapies targeting diverse immunologic pathways are being actively studied in lupus nephritis. Two promising strategies include the use of B-cell depletion therapy and multitarget therapy with calcineurin inhibitors. In parallel with the conduct of these trials, there are ongoing efforts to improve trial design. Two recent studies of outcome measures reported that a level of proteinuria of less than 0.7-0.8 g at 12 months is most predictive of good long-term renal outcome, and that the inclusion of urine red blood cells worsens the predictive value of proteinuria alone.

SUMMARY

Improved understanding of lupus nephritis pathogenesis, development of novel therapies, and optimization of clinical trial design are leading the path forward for successful drug development in lupus nephritis. The ultimate goal of these efforts is to treat our patients in a more strategic, personalized manner that improves long-term outcomes.

摘要

目的综述

狼疮肾炎是狼疮最常见的威胁器官表现,仍然导致终末期肾病。本文描述了狼疮肾炎的当代治疗方法以及新出现的治疗策略。

最近的发现

狼疮肾炎的治疗包括初始(诱导)阶段和维持(扩展)阶段,在此期间联合使用类固醇和另一种免疫抑制药物。目前的治疗方法并不完全有效,且存在较大毒性。尽管最近的几项试验结果令人失望,但针对多种免疫途径的新型疗法正在狼疮肾炎中进行积极研究。两种有前途的策略包括使用 B 细胞耗竭疗法和钙调神经磷酸酶抑制剂的多靶点治疗。在进行这些试验的同时,还在努力改进试验设计。最近的两项关于结局指标的研究报告称,12 个月时蛋白尿水平低于 0.7-0.8g 对长期肾脏结局的预测性最好,且尿红细胞的纳入会降低蛋白尿单独预测的价值。

总结

对狼疮肾炎发病机制的深入了解、新型疗法的开发以及临床试验设计的优化,为狼疮肾炎的药物开发开辟了成功的道路。这些努力的最终目标是更具策略性、个性化地治疗患者,以改善长期结局。

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