Kidney Week Educational Symposia-Opportunities and Barriers in Diagnosing CKD of Uncertain Etiology

Video Transcription

Video Summary

Dr. Susan Firth introduces a workshop on barriers and ethical considerations in genomic testing, featuring nephrologist Dr. Ali Gharavi and bioethicist Dr. John Lantos.<br /><br />Dr. Gharavi reviews how advances from microarrays to rapid, low-cost sequencing enable genetic diagnosis in chronic kidney disease (CKD). Copy-number variants (deletions/duplications) explain ~8% of pediatric and ~1.5% of adult CKD and are highly heterogeneous and often syndromic (e.g., 17q12/HNF1B with renal cysts and diabetes). In a large adult CKD exome study (~3,300 participants), diagnostic variants were found in 9.3% overall, with highest yield in congenital/cystic disease and 17% in CKD of unknown cause. Many diagnoses cluster in a few genes (PKD1/2, COL4A3-5, UMOD) but the remainder is very diverse, supporting broad exome approaches, periodic reanalysis, and careful clinical integration. He highlights cases where sequencing changed treatment (avoiding steroids in COL4-related disease) and suggests cautious interpretation for predictive testing due to false pathogenic annotations.<br /><br />Dr. Lantos discusses ethical, legal, and social issues: test accuracy (Krabbe newborn screening revealed many false positives and risky treatment tradeoffs), psychological effects (Huntington testing showed uncertainty can be most distressing), and dilemmas around returning research results. Using the CKiD study, he outlines criteria for disclosure based on analytic validity, clinical utility, age of onset, actionability, and participant preferences, emphasizing autonomy, privacy, and avoiding therapeutic misconception.

Asset Subtitle

Susan Furth, Ali Gharavi, John Lantos
Support is provided by an educational grant from Natera.

Keywords

genomic testing ethics

chronic kidney disease genetics

exome sequencing diagnostic yield

copy-number variants in CKD

HNF1B 17q12 deletion syndrome

PKD1 PKD2 COL4A3 COL4A4 COL4A5 UMOD

variant interpretation and reanalysis

return of genetic research results

newborn screening false positives (Krabbe)