Waldman M, Appel G B
Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Disease, Bethesda, Maryland 20892, USA.
Kidney Int. 2006 Oct;70(8):1403-12. doi: 10.1038/sj.ki.5001777. Epub 2006 Aug 23.
Lupus nephritis (LN) is a major cause of morbidity and mortality in patients with systemic lupus erythematosus. Although the use of aggressive immunosuppression has improved both patient and renal survival over the past several decades, the optimal treatment of LN remains challenging. Improved outcomes have come at the expense of significant adverse effects owing to therapy. Moreover with long-term survival, the chronic adverse effects of effective therapies including risk of malignancy, atherosclerosis, infertility, and bone disease all become more important. Finally, some patients fail to achieve remission with standard cytotoxic therapy and others relapse when therapy is reduced. For these reasons, recent clinical trials have attempted to define alternate treatment protocols that appear to be efficacious in achieving and maintaining remission, but with less toxicity than standard regimens. This paper discusses established and newer treatment options for patients with proliferative and membranous LN, with an emphasis on the results of these recent clinical trials. We also review the experimental and human data regarding some of the novel targeted forms of therapy that are under investigation and in different phases of clinical trials.
狼疮性肾炎(LN)是系统性红斑狼疮患者发病和死亡的主要原因。尽管在过去几十年中,积极的免疫抑制治疗提高了患者生存率和肾脏存活率,但LN的最佳治疗仍然具有挑战性。由于治疗,改善的结果是以显著的不良反应为代价的。此外,随着长期生存,有效治疗的慢性不良反应,包括恶性肿瘤风险、动脉粥样硬化、不孕和骨病,都变得更加重要。最后,一些患者采用标准细胞毒性治疗无法实现缓解,另一些患者在治疗减少时复发。由于这些原因,最近的临床试验试图确定替代治疗方案,这些方案似乎在实现和维持缓解方面有效,但毒性低于标准方案。本文讨论了增殖性和膜性LN患者已确立的和更新的治疗选择,重点是这些最近临床试验的结果。我们还回顾了关于一些正在研究且处于不同临床试验阶段的新型靶向治疗形式的实验和人体数据。