PDF(Pubmed)
Abstract：
Focal segmental glomerulosclerosis (FSGS) is a common glomerular disorder that manifests clinically with the nephrotic syndrome and has a propensity to recur following kidney transplantation. The pathophysiology and therapies available to treat FSGS currently remain elusive. Since the podocyte appears to be the target of apparent circulating factor(s) that lead to recurrence of proteinuria following kidney transplantation, this article is focused on the podocyte. In the context of kidney transplantation, the performance of pre- and post-reperfusion biopsies, and the establishment of in vitro podocyte liquid biopsies/assays allow for the development of clinically relevant studies of podocyte biology. This has given insight into new pathways, involving novel targets in innate and adaptive immunity, such as SMPDL3b, cGAS-STING, and B7-1. Elegant experimental studies suggest that the successful clinical use of rituximab and abatacept, two immunomodulating agents, in our case series, may be due to direct effects on the podocyte, in addition to, or perhaps distinct from their immunosuppressive functions. Thus, tissue biomarker-directed therapy may provide a rational approach to validate the mechanism of disease and allow for the development of new therapeutics for FSGS. This report highlights recent progress in the field and emphasizes the importance of kidney transplantation and recurrent FSGS (rFSGS) as a platform for the study of primary FSGS.
摘要：
局灶性节段性肾小球硬化（FSGS）是一种常见的肾小球疾病，在临床上表现为肾病综合征，并有肾移植后复发的倾向。可用于治疗FSGS的病理生理学和疗法目前仍然难以捉摸。由于足细胞似乎是导致肾移植后蛋白尿复发的表观循环因子的靶标，这篇文章的重点是足细胞。在肾移植的背景下，再灌注前和再灌注后活检的表现，和建立体外足细胞液体活检/测定允许发展临床相关的足细胞生物学研究。这让我们深入了解了新的途径，涉及先天和适应性免疫中的新靶标，例如SMPDL3b，cGAS-STING,B7-1优雅的实验研究表明，成功的临床使用利妥昔单抗和abatacept，两种免疫调节剂，在我们的案例系列中，可能是由于对足细胞的直接影响，此外,或者与其免疫抑制功能不同。因此，针对组织生物标志物的治疗可能提供一种合理的方法来验证疾病的机制，并允许开发FSGS的新疗法。本报告重点介绍了该领域的最新进展，并强调了肾移植和复发性FSGS（rFSGS）作为原发性FSGS研究平台的重要性。
