Parikh Samir V, Rovin Brad H
Division of Nephrology, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio.
Division of Nephrology, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio
J Am Soc Nephrol. 2016 Oct;27(10):2929-2939. doi: 10.1681/ASN.2016040415. Epub 2016 Jun 9.
The introduction of corticosteroids and later, cyclophosphamide dramatically improved survival in patients with proliferative lupus nephritis, and combined administration of these agents became the standard-of-care treatment for this disease. However, treatment failures were still common and the rate of progression to ESRD remained unacceptably high. Additionally, treatment was associated with significant morbidity. Therefore, as patient survival improved, the goals for advancing lupus nephritis treatment shifted to identifying therapies that could improve long-term renal outcomes and minimize treatment-related toxicity. Unfortunately, progress has been slow and the current approaches to the management of lupus nephritis continue to rely on high-dose corticosteroids plus a broad-spectrum immunosuppressive agent. Over the past decade, an improved understanding of lupus nephritis pathogenesis fueled several clinical trials of novel drugs, but none have been found to be superior to the combination of a cytotoxic agent and corticosteroids. Despite these trial failures, efforts to translate mechanistic advances into new treatment approaches continue. In this review, we discuss current therapeutic strategies for lupus nephritis, briefly review recent advances in understanding the pathogenesis of this disease, and describe emerging approaches developed on the basis of these advances that promise to improve upon the standard-of-care lupus nephritis treatments.
皮质类固醇的引入以及后来环磷酰胺的使用,显著提高了增殖性狼疮性肾炎患者的生存率,联合使用这些药物成为了该疾病的标准治疗方法。然而,治疗失败仍然很常见,进展为终末期肾病的比例仍然高得令人无法接受。此外,治疗还伴随着显著的发病率。因此,随着患者生存率的提高,推进狼疮性肾炎治疗的目标转向了寻找能够改善长期肾脏结局并将治疗相关毒性降至最低的疗法。不幸的是,进展缓慢,目前狼疮性肾炎的治疗方法仍然依赖于大剂量皮质类固醇加广谱免疫抑制剂。在过去十年中,对狼疮性肾炎发病机制的深入了解推动了多项新型药物的临床试验,但尚未发现任何一种药物优于细胞毒性药物和皮质类固醇的联合使用。尽管这些试验失败了,但将机制进展转化为新治疗方法的努力仍在继续。在这篇综述中,我们讨论了狼疮性肾炎的当前治疗策略,简要回顾了对该疾病发病机制的最新认识,并描述了基于这些进展而开发的有望改进狼疮性肾炎标准治疗方法的新兴方法。