Monogenic causes of chronic kidney disease in adults

Dervla M. Connaughton, Claire Kennedy, Shirlee Shril, Nina Mann, Susan L. Murray, Patrick A. Williams, Eoin Conlon, Makiko Nakayama, Amelie T. van der Ven, Hadas Ityel, Franziska Kause, Caroline M. Kolvenbach, Rufeng Dai, Asaf Vivante, Daniela A. Braun, Ronen Schneider, Thomas M. Kitzler, Brona Moloney, Conor P. Moran, John S. SmythAlan Kennedy, Katherine Benson, Caragh Stapleton, Mark Denton, Colm Magee, Conall M. O'Seaghdha, William D. Plant, Matthew D. Griffin, Atif Awan, Clodagh Sweeney, Shrikant M. Mane, Richard P. Lifton, Brenda Griffin, Sean Leavey, Liam Casserly, Declan G. de Freitas, John Holian, Anthony Dorman, Brendan Doyle, Peter J. Lavin, Mark A. Little, Peter J. Conlon, Friedhelm Hildebrandt*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Approximately 500 monogenic causes of chronic kidney disease (CKD) have been identified, mainly in pediatric populations. The frequency of monogenic causes among adults with CKD has been less extensively studied. To determine the likelihood of detecting monogenic causes of CKD in adults presenting to nephrology services in Ireland, we conducted whole exome sequencing (WES) in a multi-centre cohort of 114 families including 138 affected individuals with CKD. Affected adults were recruited from 78 families with a positive family history, 16 families with extra-renal features, and 20 families with neither a family history nor extra-renal features. We detected a pathogenic mutation in a known CKD gene in 42 of 114 families (37%). A monogenic cause was identified in 36% of affected families with a positive family history of CKD, 69% of those with extra-renal features, and only 15% of those without a family history or extra-renal features. There was no difference in the rate of genetic diagnosis in individuals with childhood versus adult onset CKD. Among the 42 families in whom a monogenic cause was identified, WES confirmed the clinical diagnosis in 17 (40%), corrected the clinical diagnosis in 9 (22%), and established a diagnosis for the first time in 16 families referred with CKD of unknown etiology (38%). In this multi-centre study of adults with CKD, a molecular genetic diagnosis was established in over one-third of families. In the evolving era of precision medicine, WES may be an important tool to identify the cause of CKD in adults.

Original languageEnglish
Pages (from-to)914-928
Number of pages15
JournalKidney International
Issue number4
StatePublished - Apr 2019


FundersFunder number
Beaumont Hospital Department of Nephrology Research Fund
Canadian Society of Nephrology
Health Research Board , IrelandHPF-206-674
National Institute of Health
National Institutes of HealthDK068306, DK088767, DK076683, U54 HG006504
National Institute of Diabetes and Digestive and Kidney DiseasesT32DK007726
ASCRS Research Foundation
Beaumont Health System
Health Research Board
Irish Nephrology SocietyT32-DK007726-33
Canadian Institutes of Health Research
Kidney Foundation of Canada
Science Foundation Ireland11/Y/B2093
Meath Foundation203170.13161
International Pediatric Research Foundation


    • chronic kidney disease
    • genetic kidney disease
    • whole exome sequencing


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