Kidney Week 2025 Early Program - Genetics in Clinical Nephrology-Genetic Testing in Kidney Transplantation

Video Transcription

Video Summary

Dr. Ali Gharavi discusses how genetic testing can be used in transplant nephrology, emphasizing diagnosis, prognosis, donor selection, pharmacogenomics, and prediction of post‑transplant comorbidities. In large chronic kidney disease (CKD) sequencing cohorts (~3,300 adults, many with end‑stage kidney disease and transplants), genetic testing provided a diagnostic yield around 9–10% across 66 genes, with common findings in PKD1/PKD2 and COL4A3-5 (Alport spectrum), plus a long “tail” of rare disorders. Yield is higher in congenital/cystic disease and notably ~17% in “kidney disease of unknown cause,” a common and frustrating category in transplant populations.  <br /><br />Guidelines recommend starting with broad CKD multigene panels (300–400 genes), then escalating to exome/genome if negative, while recognizing test limitations. Red flags for testing include family history, multi‑system disease, atypical presentations, suggestive biopsy findings, and unknown etiology.  <br /><br />Genetic results can inform prognosis (monogenic CKD progresses faster), guide donor screening within families (including consideration of APOL1 risk in African ancestry), and improve medication safety through pharmacogenomics (e.g., tacrolimus dosing). Finally, broader sequencing may reveal actionable secondary findings (e.g., BRCA2), relevant because immunosuppression increases risks like cancer; a transplant comorbidity gene panel found ~9% had predispositions affecting cardiometabolic risk, malignancy, thrombophilia, or immunodeficiency. Discussion highlights the promise of secondary findings but stresses careful consent and highly curated actionable gene lists.

Asset Subtitle

Ali Gharavi

Meta Tag

Module GENE

Speaker Ali Gharavi

Keywords

transplant nephrology

genetic testing

chronic kidney disease sequencing

multigene CKD panel

kidney disease of unknown cause

APOL1 donor risk

pharmacogenomics tacrolimus dosing