Mario Negri Institute for Pharmacological Research, Clinical Research Center for Rare Diseases Aldo e Cele Daccò, Villa Camozzi, Ranica, Bergamo, Italy.
Am J Transplant. 2013 Feb;13(2):266-74. doi: 10.1111/ajt.12045. Epub 2013 Jan 11.
Focal segmental glomerulosclerosis (FSGS) is a glomerular disease characterized by proteinuria, frequent progression to end-stage renal disease, and recurrence after kidney transplantation in ∼25% of patients, which negatively impacts long-term allograft survival. Experimental studies suggest that abnormalities in T and, possibly, B cells may represent one initial pathogenic trigger, leading to podocyte injury and progressive loss. New data also support the existence of circulating permeability factors able to damage the podocytes, but no single molecule has been consistently identified as the causal pathogenic element in FSGS recurrence. Unfortunately, major progress from mechanistic studies has not translated into substantial advancements in patient treatment, with plasmapheresis (PP) and high doses of cyclosporine (CsA) remaining the mainstays of therapy. Despite consistent experimental and clinical evidence that treatment of proteinuria slows renal function decline in proteinuric nephropathies, maximal use of antiproteinuric agents such as renin angiotensin system antagonists is not routine in the management of FSGS recurrence. More recently, encouraging results have been reported with anti-CD20 depleting antibody rituximab, but further studies are needed to establish its safety/efficacy profile.
局灶节段性肾小球硬化症（FSGS）是一种肾小球疾病，其特征是蛋白尿、频繁进展为终末期肾病，以及在约 25%的患者中肾移植后复发，这对长期移植物存活率产生负面影响。实验研究表明，T 细胞和（可能）B 细胞的异常可能代表一个初始的致病触发因素，导致足细胞损伤和进行性丧失。新数据还支持存在循环通透性因子能够损伤足细胞，但没有一种单一的分子被一致确定为 FSGS 复发的致病因素。不幸的是，从机制研究中取得的重大进展并没有转化为患者治疗的实质性进展，血浆置换（PP）和大剂量环孢素（CsA）仍然是治疗的主要方法。尽管有一致的实验和临床证据表明，治疗蛋白尿可减缓蛋白尿性肾病的肾功能下降，但在 FSGS 复发的管理中，并未常规使用最大剂量的抗蛋白尿药物，如肾素-血管紧张素系统拮抗剂。最近，用抗 CD20 耗竭抗体利妥昔单抗治疗取得了令人鼓舞的结果，但仍需要进一步的研究来确定其安全性/疗效。
