Identification of Genetic Causes of Focal Segmental Glomerulosclerosis Increases With Proper Patient Selection

Jing Miao, Filippo Pinto e Vairo, Marie C. Hogan, Stephen B. Erickson, Mireille El Ters, Andrew J. Bentall, Aleksandra Kukla, Eddie L. Greene, Loren Herrera Hernandez, Sanjeev Sethi, Konstantinos N. Lazaridis, Pavel N. Pichurin, Emily Lisi, Carri A. Prochnow, Ladan Zand, Fernando C. Fervenza

Research output: Contribution to journalArticlepeer-review


Objective: To increase the likelihood of finding a causative genetic variant in patients with a focal segmental glomerulosclerosis (FSGS) lesion, clinical and histologic characteristics were analyzed. Patients and Methods: Individuals 18 years and older with an FSGS lesion on kidney biopsy evaluated at Mayo Clinic from November 1, 1999, through October 31, 2019, were divided into 4 groups based on clinical and histologic characteristics: primary FSGS, secondary FSGS with known cause, secondary FSGS without known cause, and undetermined FSGS. A targeted gene panel and a customized gene panel retrieved from exome sequencing were performed. Results: The overall rate of detection of a monogenic cause was 42.9% (21/49). Individuals with undetermined FSGS had the highest rate of positivity (87.5%; 7/8) followed by secondary FSGS without an identifiable cause (61.5%; 8/13) and secondary FSGS with known cause (33.3%; 5/15). Four of 5 (80%) individuals in the latter group who had positive genetic testing results also had a family history of kidney disease. Univariate analysis showed that family history of kidney disease (odds ratio [OR], 13.8; 95% CI, 3.7 to 62.4; P<.001), absence of nephrotic syndrome (OR, 8.2; 95% CI, 1.9 to 58.1; P=.004), and female sex (OR, 5.1; 95% CI, 1.5 to 19.9; P=.01) were strong predictors of finding a causative genetic variant in the entire cohort. The most common variants were in the collagen genes (52.4%; 11/21), followed by the podocyte genes (38.1%; 8/21). Conclusion: In adults with FSGS lesions, proper selection of patients increases the rate of positive genetic testing significantly. The majority of individuals with undetermined FSGS in whom the clinical presentation and histologic parameters are discordant had a genetic diagnosis.

Original languageEnglish (US)
Pages (from-to)2342-2353
Number of pages12
JournalMayo Clinic proceedings
Issue number9
StatePublished - Sep 2021

ASJC Scopus subject areas

  • General Medicine


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