Clinical significance of genetic mutations in adult patients with focal segmental glomerulosclerosis
Year: 2025
Type: article
Study design: Observational Study
Abstract: Background: Steroid resistance (SR) and a family history of kidney disease (FH) are key indicators of genetic focal segmental glomerulosclerosis (FSGS) in adults. The diagnostic yield and prognostic implications of genetic testing in these patients remain unclear. Methods: The study was designed in two parts to address specific research objectives. Part 1 aimed to explore the diagnostic yield in adult FSGS patients with SR and/or FH. Part 2 aimed to investigate the clinical significance of different gene mutation types in patients with genetic FSGS. Part 1 included FSGS patients who received next-generation sequencing (NGS) because of SR and/or an FH (n = 32). According to the results of NGS, the patients were divided into the mutation group (n = 18) and the non-mutation group (n = 14). Part 2 involved patients with genetic FSGS (n = 19), who were divided into two groups: the podocyte-related gene mutation group (PO group) and the type IV collagen gene mutation group (IV-col group). The clinical, pathological, and prognostic characteristics of patients in different groups were analyzed separately. Results: In part 1, the mutation carriers showed higher FH prevalence (p = 0.027), reduced acute kidney injury (p = 0.01), milder tubulointerstitial lesions (p = 0.03), and more interstitial foam cells (p = 0.01), with foam cells emerging as a strong genetic FSGS predictor. The mutation group demonstrated superior 2-year kidney survival (p = 0.03), but no advantages in long-term kidney outcome. Part 2 revealed IV-col patients showed later onset (p = 0.03), higher serum creatinine (p = 0.01), heavier proteinuria (p = 0.02), and less hematuria (p = 0.04) vs. the PO group, though kidney outcomes showed no statistical differences. Conclusion: A diagnostic yield of 56.3% diagnostic yield supports routine genetic testing in FSGS patients with SR/FH, and the gene mutations were associated with a better short-term kidney prognosis but no differences in long-term kidney prognosis. Foam cell infiltration strongly predicts the genetic etiology of FSGS. IV-col mutations associate with insidious nephropathy onset of FSGS but similar prognosis to the podocyte mutations.
Authors: Min Min, Qiuxia Wang, Lina Zhu, Jinquan Wang, Jiong Zhang
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4417106845