What is the nephrologist’s greatest challenge in identifying, treating, and/or managing FSGS?

Dr. Fervenza: The main problem is what to do with patients who fail to respond to corticosteroids or calcineurin inhibitors. Even a kidney transplant is not a solution since the disease can recur in up to 30%-40% of patients who receive a kidney transplant.

Are there any misconceptions about the diagnosis, treatment, or management of FSGS that need to be corrected or updated?

Dr. Fervenza: To me, one of the main challenges is to be able to differentiate between primary and secondary forms of FSGS. This is important because primary FSGS is the one for which you would consider treatment with immunosuppressive therapy. On the other hand, youou would treat secondary FSGS by maximizing conservative therapy  with tight blood-pressure control with the use of angiotensin II blockade, diet, weight and lipid control, no smoking, and so forth.

How can nephrologists distinguish between primary and secondary FSGS?

Dr. Fervenza: While patients with primary FSGS characteristically have full nephrotic syndrome, those with secondary FSGS usually just have nephrotic range proteinuria—not the full syndrome. Also, electron microscopy is crucial since patients with secondary FSGS have segmental foot process effacement, while in primary FSGS effacement is usually widespread.

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Are there any telltale signs or symptoms that should prompt the nephrologist to suspect FSGS?

Dr. Fervenza: No. Patients present with proteinuria and nephrotic syndrome, which could indicate FSGS, membranous nephropathy, minimal change disease, etc. Only a renal biopsy can tell the differences.

What is the typical amount of time that elapses between development and diagnosis of FSGS?

Dr. Fervenza: It can vary from weeks to months. It depends on how acute the presentation is: Patients with sudden onset of massive edema are likely to seek medical attention earlier and get biopsied.

What has been the most significant breakthrough in FSGS research in the past five years?

Dr. Fervenza: The recognition of genetic forms of FSGS and the importance of podocyte proteins in the disease process. Another major breakthrough was the finding that apolipoprotein L1 (APOL1), which is expressed in podocytes, has a high-risk alleles prevalence in patients of African descent with primary FSGS and HIV-associated nephropathy, implicating potential podocyte effects.

What are the most critical questions that still need to be answered regarding FSGS?

Dr. Fervenza: Why do we develop primary FSGS? What is the mechanism(s)? What is the best form of treatment?