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 'genetics-first' approach for CKD, we performed genetic testing in a group of kidney transplant recipients aged <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.
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 'genetics-first' approach for CKD, we performed genetic testing in a group of kidney transplant recipients aged <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.
Authors: Steve Seltzsam; Chunyan Wang; Bixia Zheng; Nina Mann; Dervla M Connaughton; Chen-Han Wilfred Wu; Sophia Schneider; Luca Schierbaum; Franziska Kause; Caroline M Kolvenbach; Makiko Nakayama; Rufeng Dai; Isabel Ottlewski; Ronen Schneider; Konstantin Deutsch; Florian Buerger; Verena Klämbt; Youying Mao; Ana C Onuchic-Whitford; Camille Nicolas-Frank; Kirollos Yousef; Dalia Pantel; Ethan W Lai; Daanya Salmanullah; Amar J Majmundar; Stuart B Bauer; Nancy M Rodig; Michael J G Somers; Avram Z Traum; Deborah R Stein; Ankana Daga; Michelle A Baum; Ghaleb H Daouk; Velibor Tasic; Hazem S Awad; Loai A Eid; Sherif El Desoky; Mohammed Shalaby; Jameela A Kari; Hanan M Fathy; Neveen A Soliman; Shrikant M Mane; Shirlee Shril; Michael A Ferguson; Friedhelm Hildebrandt Journal: Genet Med Date: 2021-11-30 Impact factor: 8.864
Authors: Anthony J Bleyer; Maggie Westemeyer; Jing Xie; Michelle S Bloom; Katya Brossart; Jason J Eckel; Frederick Jones; Miklos Z Molnar; Wayne Kotzker; Prince Anand; Stanislav Kmoch; Yuan Xue; Samuel Strom; Sumit Punj; Zachary P Demko; Hossein Tabriziani; Paul R Billings; Trudy McKanna Journal: Am J Nephrol Date: 2022-03-24 Impact factor: 4.605
Authors: Prasad Devarajan; Glenn M Chertow; Katalin Susztak; Adeera Levin; Rajiv Agarwal; Peter Stenvinkel; Arlene B Chapman; Bradley A Warady Journal: Kidney Med Date: 2022-02-11
Authors: Amber de Haan; Mark Eijgelsheim; Liffert Vogt; Bert van der Zwaag; Albertien M van Eerde; Nine V A M Knoers; Martin H de Borst Journal: BMJ Open Date: 2022-04-07 Impact factor: 2.692
Authors: Jacqueline Soraru; Sadia Jahan; Catherine Quinlan; Cas Simons; Louise Wardrop; Rosie O'Shea; Alasdair Wood; Amali Mallawaarachchi; Chirag Patel; Zornitza Stark; Andrew John Mallett Journal: Front Med (Lausanne) Date: 2022-05-26