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Kidney Week

Abstract: TH-PO499

Combined Genetics and Ultrastructural Examination in Diagnosis and Treatment Decisions of Focal and Segmental Glomerulosclerosis

Session Information

Category: Genetic Diseases of the Kidneys

  • 1202 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Fenoglio, Roberta, CMID, Nephrology and Dialysis Unit, San Giovanni Bosco Hospital and University of Turin, Torino, Italy, Italy
  • Roccatello, Dario, CMID, Nephrology and Dialysis Unit, San Giovanni Bosco Hospital and University of Turin, Torino, Italy, Italy
Background

FSGS defines a histologic lesion that represents a pattern of injury associated to different pathologic conditions affecting both children and adults. Better understanding the role of Genetics in FSGS and response to treatment in different forms is of vital importance in this rare and multifaceted condition. We analyzed a cohort of pts with FSGS examined both with EM and genetic testing (GT). Main aims of study were: 1) assessment of GT in primary and secondary forms; 2) analysis of response to therapy according to histologic and genetic classification

Methods

This is a retrospective observational study on patients that received a histological diagnosis of FSGS, including EM, and underwent NGS genetic testing from January 2020 to June 2023. Primary and secondary forms of FSGS were distinguished by degree of pedicle fusion at EM, according to Mayo Clinic classification. Clinical, laboratory, genetic data and used therapies were recorded.

Results

33 pts receiving a histologic diagnosis of FSGS with EM examination underwent NGS testing. Of these, 25 had available genetic results and were included. Ten patients were females, 15 were males; mean age was 40.8 years; 20 were Caucasian, 4 Black, 1 Asian. Based on EM, 11 were classified as primary forms, 14 as secondary forms. 12 patients presented with nephrotic syndrome (10 had a primary form). 7 had nephrotic range proteinuria, 6 had subnephrotic proteinuria. 6 primary and 8 secondary forms had a positive GT (p=0.78). All primary forms received immunosuppressive therapies (rituximab-based regimens); all secondary forms received support therapy. 9 primary and 9 secondary forms had at least a PR to treatment (4 CR in primary and 1 CR in secondary group) (p=0.33). Among primary forms, 5 of 6 patients with a positive GT had at least a PR with a strong immunosuppressive therapy. In secondary forms group 4 of 8 patients had at least PR with offered support therapy.

Conclusion

Percentage of positive GT did not differ in primary and secondary forms of FSGS as defined by Mayo Clinic classification. Thus a positive GT should not be considered a unique feature of secondary forms. In conclusion, as clinical presentation and light microscopy are not sufficient for an accurate diagnosis, combining EM and GT is of utmost importance in proper classification and management of FSGS.