Kidney Health Initiative (KHI)

KHI Current Project

Surrogate Endpoints in FSGS

Patient Care Issue:

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.

Challenge:

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.

KHI Solution:

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.

Status:

Open Call for Workgroup Members

To apply to serve on this workgroup, please send the following materials in an email to khi@asn-online.org with a subject "FSGS Workgroup":

  1. Name and contact information
  2. CV or Resume
  3. Brief description of why you would like to participate (250 words or less)
  4. Brief description of what you will contribute (250 words or less)
  5. Note your interest in serving as chair, member, or either position

Deliverable:

Publication(s)

Timeframe for Completion

Fall 2018

Workgroup:

TBD

Selected References:
  1. Korbet, S. M. (2002) Treatment of primary focal segmental glomerulosclerosis. Kidney Int, 62, 2301-10., 2002
  2. D'Agati VD et al. Focal segmental glomerulosclerosis. N Eng J Med 2011 Dec 22;365(25):2398-411.; Rosenberg et al. Glomerular Disease: Focal Segmental Glomerulosclerosis. cJASN 12:502-517, 2017.
  3. 2014 USRDS ESRD Database http://www.usrds.org/2014/view/v2_07.aspx (accessed 12/13/2015)
  4. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney inter., Suppl. 2012; 2: 139–274.
  5. Spino C et al. Changing the paradigm for the treatment and development of new therapies for FSGS. Front Pediatr 4: 25, 2016.

If you have any questions, please do not hesitate to contact KHI at khi@asn-online.org.