Mariani Laura H, Trachtman Howard, Thompson Aliza, Gillespie Barbara S, Denburg Michelle, Diva Ulysses, Geetha Duvuru, Greasley Peter J, Hladunewich Michelle A, Huizinga Robert B, Inrig Jula K, Komers Radko, Laurin Louis-Philippe, Little Dustin J, Nachman Patrick H, Smith Kimberly A, Walsh Liron, Gibson Keisha L
Renal Division, University of Michigan, Ann Arbor, Michigan.
Department of Pediatrics/Nephrology, University of Michigan, Ann Arbor, Michigan.
Am J Kidney Dis. 2025 May;85(5):610-617. doi: 10.1053/j.ajkd.2024.08.011. Epub 2024 Oct 23.
Focal segmental glomerulosclerosis (FSGS) is a characteristic histopathological lesion that is indicative of underlying glomerular dysfunction. It is not a single disease entity but rather a heterogeneous disorder that is an important cause of nephrotic syndrome and kidney failure in children and adults. The aim of this Kidney Health Initiative project was to evaluate potential end points for clinical trials in FSGS. Our focus is on the data supporting proteinuria as a surrogate end point. Available data support the use of complete remission of proteinuria in patients with heavy proteinuria as a surrogate end point for progression to kidney failure. Substantial treatment effects on proteinuria that are short of a complete remission may also predict the effect of a treatment on progression to kidney failure, but further work is needed to determine how such an end point should be defined. Fortunately, efforts are underway to bring together patient-level data from randomized controlled trials, observational studies, and registries to address this issue.
局灶节段性肾小球硬化(FSGS)是一种特征性的组织病理学病变,提示潜在的肾小球功能障碍。它不是单一的疾病实体,而是一种异质性疾病,是儿童和成人肾病综合征及肾衰竭的重要原因。本肾脏健康倡议项目的目的是评估FSGS临床试验的潜在终点。我们关注的是支持蛋白尿作为替代终点的数据。现有数据支持将重度蛋白尿患者的蛋白尿完全缓解作为进展至肾衰竭的替代终点。对蛋白尿有显著治疗效果但未完全缓解的情况也可能预测治疗对进展至肾衰竭的影响,但还需要进一步研究来确定应如何定义这样一个终点。幸运的是,目前正在努力整合来自随机对照试验、观察性研究和登记处的患者水平数据以解决这一问题。