Kidney Week 2025 Early Program - Genetics in Clinical Nephrology-Genetic Evaluation of Patients with Kidney Stones

Video Transcription

Video Summary

Monogenic urinary stone disease causes a small but important subset of kidney stones (≈2% of adults, ≈10% of children; higher with consanguinity) and is typically more severe, with earlier onset, frequent recurrence, renal insufficiency, and extra‑renal features. Around 40 genes are known. Genetic testing should be considered in all pediatric stone/nephrocalcinosis cases, and in adults with additional red flags such as family history, unexplained kidney failure, growth or bone disease, unusual stone type, proteinuria, low GFR, hypercalciuria, hyperoxaluria, or cysts. Testing enables definitive diagnosis, family counseling, tailored management, and access to trials; gene-specific therapies are emerging (e.g., RNA therapy for primary hyperoxaluria type 1). The talk reviews key disorders (Dent disease, primary hyperoxaluria, APRT deficiency, cystinuria, and vitamin D/phosphate pathway defects) and shows that targeted next-generation sequencing panels efficiently yield diagnoses (about 36% in a 453-family cohort), including copy-number variants. Rare and common variants in monogenic stone genes also contribute to typical stone risk.

Asset Subtitle

Peter C. Harris

Keywords

monogenic urinary stone disease

genetic testing kidney stones

targeted next-generation sequencing panels

primary hyperoxaluria RNA therapy

cystinuria and Dent disease

APRT deficiency and vitamin D/phosphate pathway defects