Kidney Week 2025 Early Program - Glomerular Diseases: 2025 Update-How Genetic Testing Informs Glomerular Disease Diagnosis and Therapy in 2025

Video Transcription

Video Summary

Dr. Benjamin Wooden (Columbia University) explains how genetic testing is increasingly practical and valuable for diagnosing and managing glomerular diseases, especially FSGS. He presents a case of a 24-year-old woman with nephrotic-range proteinuria and an FSGS biopsy pattern that didn’t clearly fit primary or secondary FSGS, leading to uncertainty about prognosis and whether to use immunosuppression. Genetic testing was used to clarify the diagnosis.<br /><br />He reviews common testing approaches, emphasizing next-generation sequencing (NGS): targeted gene panels, whole exome sequencing, and whole genome sequencing. Results typically return as: (1) diagnostic pathogenic/likely pathogenic variants, (2) variants of uncertain significance (VUS), (3) carrier findings, or (4) secondary actionable findings (per ACMG guidance). He outlines a practical workflow: positive results should prompt genetic counseling and disease-specific management; VUS may require further investigation and possible reclassification; negative results should be interpreted in light of remaining suspicion and potential false negatives (e.g., missing genes on panels or noncoding variants), sometimes warranting whole genome sequencing.<br /><br />He categorizes monogenic glomerular disorders into podocytopathies, GBM disorders (including Alport), complementopathies (aHUS/C3G), other conditions (e.g., Fabry), and risk alleles (notably APOL1). Genetic diagnoses can avoid unnecessary immunosuppression, improve prognostication, guide surveillance for extrarenal disease, affect transplant recurrence risk, and inform living donor evaluation. In the case, testing revealed NPHS2 variants explaining later-onset disease, supporting supportive rather than immunosuppressive therapy.

Asset Subtitle

Benjamin Wooden

Meta Tag

Module GLOM

Speaker Benjamin Wooden

Keywords

genetic testing

glomerular diseases

focal segmental glomerulosclerosis (FSGS)

next-generation sequencing (NGS)

NPHS2 variants

variants of uncertain significance (VUS)

transplant recurrence risk