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探索狼疮性肾炎治疗的新途径。

Towards new avenues in the management of lupus glomerulonephritis.

机构信息

Department of Medicine, Tuen Mun Hospital, 23 Tsing Chung Koon Road, New Territories, Hong Kong SAR, China.

出版信息

Nat Rev Rheumatol. 2016 Apr;12(4):221-34. doi: 10.1038/nrrheum.2015.174. Epub 2016 Jan 5.

Abstract

Renal involvement in systemic lupus erythematosus (SLE) carries substantial morbidity and mortality. Conventional immunosuppressive agents (cyclophosphamide and azathioprine) have suboptimal efficacy and substantial toxicity. Mycophenolate mofetil has emerged as an alternative agent for both induction and maintenance therapy in lupus nephritis because of its reduced gonadal toxicity, despite its failure to demonstrate superiority over cyclophosphamide in pivotal studies. The calcineurin inhibitor tacrolimus has equivalent efficacy to cyclophosphamide and mycophenolate mofetil for inducing remission of lupus nephritis. Although rituximab has shown promise in refractory lupus nephritis, combining rituximab with mycophenolate mofetil as initial therapy offers no additional benefit. Considerable interethnic variation is evident in the efficacy and tolerability of the various immunosuppressive regimens, which necessitates individualized treatment and comparison of the efficacy of new regimens across different ethnic groups. For example, low-dose combinations of tacrolimus and mycophenolate mofetil seem to be more effective than pulse cyclophosphamide as induction therapy in Chinese patients. The same regimen has also been used successfully to treat refractory proliferative and membranous lupus nephritis in patients of various ethnic groups. Finally, novel serum and urinary biomarkers are being validated for diagnosis, prognostic stratification and early recognition of flares in lupus nephritis.

摘要

系统性红斑狼疮(SLE)的肾脏受累会带来严重的发病率和死亡率。传统的免疫抑制剂(环磷酰胺和硫唑嘌呤)疗效不佳,且毒性较大。霉酚酸酯因其性腺毒性较低,已成为狼疮肾炎诱导和维持治疗的替代药物,尽管其在关键研究中未能显示优于环磷酰胺的疗效。钙调神经磷酸酶抑制剂他克莫司在诱导狼疮肾炎缓解方面与环磷酰胺和霉酚酸酯等效。尽管利妥昔单抗在难治性狼疮肾炎中显示出前景,但将利妥昔单抗与霉酚酸酯联合作为初始治疗并不能带来额外的益处。各种免疫抑制剂方案的疗效和耐受性在不同种族之间存在明显差异,这需要个体化治疗,并比较不同种族新方案的疗效。例如,在中国人中,低剂量他克莫司和霉酚酸酯联合方案似乎比脉冲环磷酰胺更有效作为诱导治疗。该方案也已成功用于治疗各种族患者的难治性增生性和膜性狼疮肾炎。最后,新型血清和尿液生物标志物正在验证中,用于狼疮肾炎的诊断、预后分层和早期识别复发。

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