Proteinuria reduction as a surrogate end point in trials of IgA nephropathy

Abstract

IgA nephropathy (IgAN) is an important cause of ESKD for which there are no approved therapies. A challenge for evaluating treatments for IgANis the usual long time course for progression to ESKD. The aimof this Kidney Health Initiative projectwas toidentify surrogate endpoints thatcouldserve as reliable predictorsofa treatment’s effecton long-termkidney outcomes inIgANandbe used as abasis for approval. Proteinuriawas identifiedas themost widely recognized andwell studied risk factor for progression to ESKDin IgAN. Theworkgroup performed a critical review of the data on proteinuria reduction as a surrogate endpoint for a treatment’s effect on progression to ESKDin IgAN. Epidemiologic data indicate a strong and consistent relationship between the level and duration of proteinuria and loss of kidney function. Trial-level analyses of data from 13 controlled trials also show an association between treatment effects on percent reduction of proteinuria and treatment effects on a composite of time to doubling of serum creatinine, ESKD, or death.Weconclude that data support the use of proteinuria reduction as a reasonably likely surrogate endpoint for a treatment’s effectonprogression toESKDin IgAN.In theUnited States, reasonably likely surrogate end points can be used as a basis for accelerated approval of therapies intended to treat serious or life-threatening conditions, such as IgAN. The clinical benefit of products approved under this program would need to be verified in a postmarketing confirmatory trial.