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Abstract: PO1617

Positive Identification of Genetic Causes of FSGS Increases with Proper Patient Selection

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Miao, Jing, Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, United States
  • Zand, Ladan, Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, United States
  • Vairo, Filippo, Department of Clinical Genomics and Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, United States
  • Hogan, Marie C., Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, United States
  • Erickson, Stephen B., Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, United States
  • Prochnow, Carri, Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, United States
  • El Ters, Mireille, Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, United States
  • Bentall, Andrew J., Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, United States
  • Kukla, Aleksandra, Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, United States
  • Greene, Eddie L., Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, United States
  • Herrera hernandez, Loren Paola, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States
  • Sethi, Sanjeev, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States
  • Fervenza, Fernando C., Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, United States
Background

FSGS is a histological lesion with diverse pathogenesis, commonly divided into primary, secondary (maladaptive, virus or drugs), and genetic forms. Differentiation of these forms is challenging but important for management and prognosis. We aimed to identify clinicopathologic factors that could be predictive of finding a genetic diagnosis in individuals with unknown forms of FSGS.

Methods

Cohort study included 51 FSGS patients with either a “secondary” form of FSGS without an identifiable cause or with presumed “primary” FSGS who failed to respond to immunosuppressive therapy (IS). Seven patients with primary FSGS in remission following IS served as negative control. Patients were classified as having pathogenic/likely pathogenic variants (Group 1a), relevant variants of uncertain significance (relevant VUS; Group 1b), and no relevant variants (Group 2). Clinicopathologic characteristics are presented in Table 1.

Results

A pathogenic/likely pathogenic genetic variant or relevant VUS was found in 41.2% (n=21/51) and in 11.8% (n=6/51) of the patients, respectively. 55.6% were in COL4A (A3/A4/A5/A1), 33.3% in podocyte genes (INF2/NPHS2/TRPC6/NPHS1), and 11.1% in other genes (DLC1/SMARCAL1/UMOD). Family history of kidney disease was present in 75% (n=15/20) of the patients in Group 1a, 16.7% (n=1/6) in Group 1b, 20.8% (n=5/24) in Group 2 and 0% (n=0/7) in the negative control. There was a negative correlation between proteinuria and the probability of finding a genetic variant. Severe foot process effacement on EM and nephrotic syndrome were significantly more common in the negative control group compared to Group 1a.

Conclusion

Over 50% of adult patients with FSGS who could not be categorized into primary or known secondary forms were found to have a genetic diagnosis. Positive family history and absence of nephrotic syndrome increased the likelihood of identifying a pathogenic/likely pathogenic variant. Genetic testing is therefore highly recommended in such population.

Table 1