Focal segmental glomerulosclerosis (FSGS) is a rare glomerular disorder which may result in extreme proteinuria and rapid progression to end-stage renal-disease. FSGS can present in a variety of ways varying from proteinuria to arterial hypertension, edema and nephrotic syndrome and can progress to ESRD over the course of 5-10 years¹. FSGS is a leading and growing cause of nephrotic syndrome worldwide ² and accounts for 3-4% of prevalent ESRD in the United States ³.

At present, there are no FDA-approved treatments for FSGS. Potential predictors of more rapidly progressive disease have included demographics, genetics, higher baseline proteinuria, histopathologic type, and response to treatment (remission status). Reduction in proteinuria is regarded as beneficial and is the primary goal of treatment to slow the progressive course of FSGS. Current treatment is inhibition of the renin-angiotensin-aldosterone system followed by steroids and potentially immunosuppressives.

Despite the relatively rapid decline in renal function among patients with FSGS, few randomized, controlled trials have been conducted, and guidelines for the treatment of FSGS remain based on generally low-level evidence ⁴. This is in part due to fact that the disease is rare and requirement of demonstrating a treatment effect on the "hard endpoints" of ESRD or a halving of eGFR or death would require too large and too long of a trial to be feasible. Thus, there is a recognized need to identify an earlier surrogate endpoint that could be used in clinical trials to establish the efficacy of therapies for patients with FSGS who are at high risk of progressing to ESRD ⁵.

The working group will seek to identify potential short-term and intermediate candidate surrogate outcome measures by: 1) performing a critical review of the literature in FSGS, focused on prospective cohort studies and prospective interventional clinical trials; and 2) analyzing data from available FSGS databases.