Proteinuria as an End Point in Clinical Trials of Focal Segmental Glomerulosclerosis

Abstract

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.

Keywords: Clinical trials; focal segmental glomerulosclerosis (FSGS); proteinuria; surrogate end points.