The scar tissue that forms on sections of some glomeruli in focal segmental glomerulosclerosis (FSGS) will lead to kidney failure if left untreated.

Nephrologist Fernando C. Fervenza, MD, PhD, is a site principal investigator currently recruiting participants at Mayo Clinic in Rochester, Minn., for a Genzyme-sponsored phase 2 study comparing the human monoclonal antibody fresolimumab with placebo in patients with steroid-resistant primary FSGS ( identifier: NCT01665391; information available here). Dr. Fervenza recently discussed the challenges of FSGS management with Renal & Urology News.

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How did you become interested in studying FSGS?

Dr. Fervenza: To me, glomerular diseases are the quintessential kidney disease, and FSGS is one of these  diseases. I also believe is an area where patients have the best probability of getting treatment or achieving a cure.

How common is FSGS in the United States?

Dr. Fervenza: It is a common form of glomerular disease—it is either the first- or second-leading cause of nephrotic syndrome due to a primary glomerular disease. I do not know the exact numbers, but some studies suggest that the prevalence of idiopathic FSGS in adults may be increasing: It was found in 2.5% to 4% of native renal biopsies in the 1970s, but in 12.2% to 18.7% in the 2000s, making FSGS the most common diagnosis based on native kidney biopsies.

So FSGS incidence is on the rise?

Dr. Fervenza: Recent studies of renal biopsy archives in the United States suggest that the incidence of FSGS has increased, with the greatest incidence rates in the African-American population. But the increase in incidence has also been observed in whites and other races.

What are the main drivers of this increase?

Dr. Fervenza: It may be due to real increases in true FSGS incident rates, differences in reporting, changes in biopsy practice and disease classification, data base inclusion criteria, and U.S. demographics. That said, population-based studies of incident glomerular diseases are needed before we could say for sure that incidence rate for FSGS has increased in the U.S. population.

Urbanization and the progressive increase in the frequency of obesity may play a role in the rising incidence of FSGS. However, obesity is unlikely to be the major factor to account for increasing incidence of FSGS, and involvement of yet-unidentified new environmental factors in the causation of FSGS remains an intriguing possibility.

What environmental factors are on your list of suspects?

I think food additives, such as growth hormone given to animals and pesticides, may be involved. I have no proof, of course. But how can we explain the increase in numbers?

What is the current gold-standard treatment for FSGS?

Dr. Fervenza: There is no gold standard. In patients with primary FSGS, high-dose corticosteroids or calcineurin inhibitors can be used, but to me there is no study on which you could base a decision regarding which one to use first.