Utility of Genetic Testing in Adults with CKD

Key Points Diagnostic yield of genetic testing in adults with CKD is 40%. Risk factors including positive family history and extra-kidney features associate with higher diagnostic yield, although young age at testing did not. Seventeen percent of patients who received a genetic diagnosis were reclassified into a different phenotype after testing. Background Clinical and pathological confirmation of the diagnosis for CKD has limitations, with up to one third of individuals remaining without a formal diagnosis. Increasingly, data suggest that these limitations can be overcome by genetic testing. The objective of this study was to estimate the diagnostic yield of genetic testing in adults with CKD. Methods Cohort studies that report diagnostic yield of genetic testing in adults with CKD published in PubMed or Embase between January 1, 2005, and December 31, 2023, were included. The Joanna Briggs Institute critical appraisal tool for prevalence studies was used to assess bias. Duplicate independent data extraction and a meta-analysis of proportions using generalized linear mixed models were completed. Results We included 60 studies with 10,107 adults with CKD who underwent genetic testing. We found a diagnostic yield of 40% (95% confidence interval, 33 to 46); yield varied by CKD subtype with the highest yield of 62% (95% confidence interval, 57 to 68) in cystic kidney disease. Positive family history and presence of extra-kidney features were associated with higher diagnostic yield. Reclassification of the before testing diagnosis after a positive genetic testing result occurred in 17% of the solved cohort. Six studies showed the clinical benefits of genetic testing including cascade testing for family members and treatment changes. Conclusions Overall, we show that genetic testing is informative in a high proportion of clinically selected adults with CKD. The study was limited by heterogeneity in reporting, testing technologies, and cohort characteristics. Clinical Trial registry name and registration number: International prospective register of systematic reviews (CRD42023386880).