Passerini P
U.O. Nefrologia, Ospedale Maggiore IRCCS, Milan.
G Ital Nefrol. 2004 Nov-Dec;21(6):531-9.
Corticosteroids and cytotoxic agents have been largely used in idiopathic membranous nephropathy (MN). A meta-analysis of controlled studies with corticosteroids did not demonstrate any benefit in using these agents on disease outcome. On the contrary, some controlled trials reported that cytotoxic agents can significantly reduce proteinuria. Three multicenter randomized controlled studies demonstrated that a regimen based on a 6-month treatment alternating every other month methylprednisolone with chlorambucil or cyclophosphamide, not only favors nephrotic syndrome remission, but can also protect long-term renal function. Cyclosporine has also been shown to be effective in inducing a partial or the complete remission of nephrotic syndrome. The main problem with cyclosporine is that in many responders proteinuria relapses when the drug is stopped. However, if the drug is given for a prolonged period and is tapered off gradually the risk of relapse can be reduced. A recent study showed that treatment with a long acting ACTH preparation for 1 yr was associated with significant long-term improvements in serum lipoprotein patterns, urinary protein excretion and glomerular function. Unfortunately, the study was not randomized, the number of patients was small and the follow-up was short. Advances in understanding the pathogenetic mechanisms of glomerulonephritis produced specifically new approaches to selected cell types or molecular pathways involved in MN pathogenesis. These therapies should guarantee therapeutic efficacy while limiting the adverse effects of non-selective immunosuppression. However, we need randomized clinical trials to ascertain how well they perform in practice rather than just on a theoretical basis.
皮质类固醇和细胞毒性药物已广泛应用于特发性膜性肾病(MN)。一项关于皮质类固醇对照研究的荟萃分析未显示使用这些药物对疾病转归有任何益处。相反,一些对照试验报告称细胞毒性药物可显著降低蛋白尿。三项多中心随机对照研究表明,一种基于每隔一个月交替使用甲泼尼龙与苯丁酸氮芥或环磷酰胺进行6个月治疗的方案,不仅有利于肾病综合征缓解,还能保护长期肾功能。环孢素也已被证明对诱导肾病综合征部分或完全缓解有效。环孢素的主要问题是,在许多有反应者中,停药后蛋白尿会复发。然而,如果长期给药并逐渐减量,复发风险可以降低。最近一项研究表明,用长效促肾上腺皮质激素制剂治疗1年与血清脂蛋白模式、尿蛋白排泄和肾小球功能的显著长期改善有关。不幸的是,该研究未随机分组,患者数量少且随访时间短。在理解肾小球肾炎发病机制方面的进展产生了针对MN发病机制中特定细胞类型或分子途径的新方法。这些疗法应在保证治疗效果的同时限制非选择性免疫抑制的不良反应。然而,我们需要随机临床试验来确定它们在实际应用中的效果如何,而不仅仅是基于理论基础。