Beyond the kidney biopsy: genomic approach to undetermined kidney diseases

ABSTRACT Background According to data from large national registries, almost 20%–25% of patients with end-stage kidney disease have an undetermined (UKD). Recent shown that monogenic disease-causing variants are under-diagnosed. We performed exome sequencing (ES) on UKD in our center improve the diagnosis rate. Methods ES was proposed routine practice for including biopsy January 2019 December 2021. Mutations were detected using a targeted bioinformatic customized gene panel (675 genes). The pathogenicity assessed American College Medical Genetics guidelines. Results included 230 adult patients, median age 47.5 years. Consanguinity reported by 25 patients. A family history documented 115 (50%). Kidney biopsies either inconclusive 69 (30.1%) or impossible 71 (30.9%). 28 renal disorders 75 (32.6%) Collagenopathies most common genetic (46.7%), COL4A3 and COL4A4 accounting 80% these diagnoses. Tubulopathies (16%) ciliopathies (14.7%) yielded, respectively, second third category UMOD-associated nephropathy as main findings tubulopathies (7/11). Ten 22 having “first” eventually received positive diagnosis, thereby avoiding 11 biopsies. Among 44 glomerular, tubulo-interstitial vascular nephropathy, 13 (29.5%) phenocopies. diagnostic yield higher female (P = .02) < .0001), reaching 56.8% when patient had both first- second-degree disease. Conclusion Genetic has provided new clinical insights clarifying reclassifying etiology over Exome may significant yield, thus invasive biopsy; moreover, remains elevated even is inconclusive. provides benefit nephrological healthcare UKD.