Kidney Week 2025 Early Program - Genetics in Clinical Nephrology-Updates on Genetic Kidney Diseases

Video Transcription

Video Summary

The speaker presents a 28-year-old man with CKD, new-onset diabetes, hypomagnesemia, small renal cysts, and an atrophic kidney—features suggesting possible genetic kidney disease despite limited family history. They review evidence that ~10% of adults with CKD have monogenic causes, most commonly ADPKD or Alport syndrome, but many cases involve individually rare genes. The talk highlights when genetic testing has highest yield: unknown etiology (especially young patients), syndromic/extrarenal features, suggestive biopsy findings (e.g., FSGS, GBM abnormalities, TMA), cystic disease with atypical features, and even absent family history.<br /><br />They summarize KDIGO/NKF guidance emphasizing that nephrologists should provide pre- and post-test counseling, covering benefits (targeted therapies, altered supportive care, avoiding ineffective immunosuppression, transplant planning, screening for extrarenal disease, family planning, sometimes avoiding biopsy) and risks (limits of GINA for life/disability/long-term care insurance; false negatives/indeterminate results).<br /><br />Testing strategy typically starts with a broad kidney gene panel unless a known familial variant exists; CACUT may warrant microarray. The case reveals a likely pathogenic HNF1B deletion explaining the phenotype, plus incidental carrier status for PKHD1 and a VUS in an RTA gene. The speaker explains variant classes (pathogenic to benign), stresses VUS are clinically indeterminate, and notes rapid progress from AI prediction, larger diverse databases, updated guidelines, and scalable functional assays. They conclude with current and emerging targeted therapies (small molecules, siRNA, antisense, future gene therapy) and discuss challenges like VUS reanalysis responsibility and building clinical genetics infrastructure.

Asset Subtitle

Gabriel Loeb

Meta Tag

Module GENE

Speaker Gabriel Loeb

Keywords

chronic kidney disease (CKD)

monogenic kidney disease

genetic testing in nephrology

HNF1B deletion

renal cysts and diabetes syndrome

KDIGO/NKF genetic counseling

variant of uncertain significance (VUS)

targeted therapies (siRNA/antisense)