Genetics-first approach improves diagnostics of ESKD patients <50 years old. Issue 2 (11th December 2020)

• Record Type: Journal Article
• Authors: Snoek, Rozemarijn; van Jaarsveld, Richard H; Nguyen, Tri Q; Peters, Edith D J; Elferink, Martin G; Ernst, Robert F; Rookmaaker, Maarten B; Lilien, Marc R; Spierings, Eric; Goldschmeding, Roel; Knoers, Nine V A M; van der Zwaag, Bert; van Zuilen, Arjan D; van Eerde, Albertien M
• Is Part Of: Nephrology dialysis transplantation. Volume 37:Issue 2(2022)
• Page Start: 349
• Page End: 357
• Publication Date: 2020-12-11
• Subjects: chronic kidney disease -- genetics -- kidney biopsy -- kidney transplant; Nephrology -- Periodicals; Hemodialysis -- Periodicals; Kidneys -- Transplantation -- Periodicals; Hemodialysis; Kidneys -- Transplantation; Nephrology; Periodicals; 616.61
• DOI: 10.1093/ndt/gfaa363
• Languages: English
• ISSNs: 0931-0509

Abstract

Abstract: Background: Often only chronic kidney disease (CKD) patients with high likelihood of genetic disease are offered genetic testing. Early genetic testing could obviate the need for kidney biopsies, allowing for adequate prognostication and treatment. To test the viability of a &#39;genetics-first&#39; approach for CKD, we performed genetic testing in a group of kidney transplant recipients aged &lt;50 years, irrespective of cause of transplant. Methods: From a cohort of 273 transplant patients, we selected 110 that were in care in the University Medical Center Utrecht, had DNA available and were without clear-cut non-genetic disease. Forty patients had been diagnosed with a genetic disease prior to enrollment; in 70 patients, we performed a whole-exome sequencing-based 379 gene panel analysis. Results: Genetic analysis yielded a diagnosis in 51%. Extrapolated to the 273 patient cohort, who did not all fit the inclusion criteria, the diagnostic yield was still 21%. Retrospectively, in 43% of biopsied patients, the kidney biopsy would not have had added diagnostic value if genetic testing had been performed as a first-tier diagnostic. Conclusions: The burden of monogenic disease in transplant patients with end-stage kidney disease (ESKD) of any cause prior to the age of 50 years is between 21% and 51%. Early genetic testing can provide a non-invasive diagnostic, impacting prognostication and treatment, and obviating the need for an invasive biopsy. We conclude that in patients who expect to develop ESKD prior to the age of 50 years, genetic testing should be considered as first mode of diagnostics.