Kidney Week 2025 Early Program - Genetics in Clinical Nephrology-Unraveling Rare Kidney Diseases: Rare Diseases Registry Program (RaDaR) and 100,000 Genomes Project

Unraveling Rare Kidney Diseases: Rare Diseases Registry Program (RaDaR) and 100,000 Genomes Project

Video Transcription

Video Summary

Professor Daniel Gale describes how UK population-scale genomics and longitudinal registries are transforming understanding and treatment development for rare kidney diseases. Although rare diseases represent a small fraction of chronic kidney disease overall, they account for a large share of kidney failure, especially in children, and drive major healthcare costs.<br /><br />He explains how the UK 100,000 Genomes Project (120,000 whole genomes linked to NHS records) enables inclusive case-control analyses across ancestries and reveals both Mendelian and non-Mendelian genetic contributions. Examples include associations for posterior urethral valves, additive effects of rare SLC34A3 variants plus polygenic risk in kidney stones, differing effect sizes across cystic kidney disease genes (from highly penetrant PKD1/PKD2 to lower-risk IFT140), and genetic diagnoses in ~17% of unexplained early kidney failure, with strong APOL1 effects in African ancestry.<br /><br />He then highlights the RADAR Registry (38,000 consented participants, linked labs/outcomes, recontactable for trials) as a platform to quantify disease burden, map eGFR trajectories, validate surrogate endpoints (notably proteinuria change predicting long-term kidney failure risk), inform NICE/FDA decisions, and enable trial recruitment. A proof-of-mechanism Alport trial of a stop-codon read-through drug showed restored collagen staining in all three recruited patients. He concludes with the UK “genomic medicine service” feedback loop linking care, research, variant reclassification, and clinical trials, plus newborn genome screening initiatives.

Asset Subtitle

Daniel Gale

Meta Tag

Module GENE

Speaker Daniel Gale

Keywords

UK population genomics

100,000 Genomes Project

rare kidney diseases

RADAR Registry

whole-genome sequencing linked to NHS records

proteinuria surrogate endpoint

APOL1 genetic risk