Pediatr Nephrol. 2012 Dec;27(12):2163-6. doi: 10.1007/s00467-012-2218-5. Epub 2012 Jul 18.
Steroid resistant nephrotic syndrome (SRNS), otherwise termed focal segmental glomerulosclerosis (FSGS) is one of the most difficult conditions to manage for the nephrologist, particularly when the disease recurs post-transplantation. It is also fascinating from the biological perspective, as the non-genetic form appears highly likely to be caused by a disorder of circulating plasma, leading to the search for the elusive 'plasma factor' over several decades of research. Many hypotheses have been proposed and tested, and to date none have yet passed the test of clinical utility. The search appears to be narrowing, aided by landmark discoveries in the molecular properties of the glomerular filtration barrier, and improved experimental tools. Therapeutically we are also more able to target specific molecules, for example by monoclonal antibody treatments. In this context, the report of the effects of TNF-α on podocytes is instructive. This tells us that this cytokine could have directly deleterious effects on podocytes in vivo, and that this effect can be targeted clinically, potentially halting or reversing the disease process. As with all thought provoking research, this raises several interesting questions. Is TNF-α the elusive 'factor' or is it one of several? Is it directly affecting the glomerular filtration barrier, or modulating the immune response? And could this technique be used as a cell based assay for disease activity? This report adds to the growing list of candidates that need to be tested in a wider population of well phenotyped patients with SRNS. [corrected].
激素抵抗性肾病综合征（SRNS），又称局灶节段性肾小球硬化症（FSGS），是肾病学家最难治疗的病症之一，尤其是在疾病移植后复发时。从生物学角度来看，这种疾病也很有趣，因为非遗传性形式似乎很可能是由循环血浆紊乱引起的，这导致在几十年的研究中一直在寻找难以捉摸的“血浆因子”。已经提出并测试了许多假设，但迄今为止，没有一个假设通过了临床实用性的测试。由于在肾小球滤过屏障的分子特性方面取得了里程碑式的发现，并改进了实验工具，搜索范围似乎正在缩小。在治疗方面，我们也更能够针对特定分子，例如通过单克隆抗体治疗。在这种情况下，关于 TNF-α 对足细胞的影响的报告具有启发性。这告诉我们，这种细胞因子可能对体内足细胞有直接的有害影响，并且这种作用可以在临床上进行靶向治疗，从而有可能阻止或逆转疾病进程。与所有发人深省的研究一样，这提出了几个有趣的问题。TNF-α 是难以捉摸的“因子”，还是其中之一？它是否直接影响肾小球滤过屏障，还是调节免疫反应？这种技术是否可以用作疾病活动的基于细胞的测定？该报告增加了需要在具有 SRNS 的表型良好的更广泛人群中进行测试的候选物的数量。[更正]。
