The utility of a genetic kidney disease clinic employing a broad range of genomic testing platforms: experience of the Irish Kidney Gene Project

Elhussein A.E. Elhassan, Susan L. Murray, Dervla M. Connaughton, Claire Kennedy, Sarah Cormican, Cliona Cowhig, Caragh Stapleton, Mark A. Little, Kendrah Kidd, Anthony J. Bleyer, Martina Živná, Stanislav Kmoch, Neil K. Fennelly, Brendan Doyle, Anthony Dorman, Matthew D. Griffin, Liam Casserly, Peter C. Harris, Friedhelm Hildebrandt, Gianpiero L. CavalleriKatherine A. Benson, Peter J. Conlon

Research output: Contribution to journalArticlepeer-review

Abstract

Background and aims: Genetic testing presents a unique opportunity for diagnosis and management of genetic kidney diseases (GKD). Here, we describe the clinical utility and valuable impact of a specialized GKD clinic, which uses a variety of genomic sequencing strategies. Methods: In this prospective cohort study, we undertook genetic testing in adults with suspected GKD according to prespecified criteria. Over 7 years, patients were referred from tertiary centres across Ireland to an academic medical centre as part of the Irish Kidney Gene Project. Results: Among 677 patients, the mean age was of 37.2 ± 13 years, and 73.9% of the patients had family history of chronic kidney disease (CKD). We achieved a molecular diagnostic rate of 50.9%. Four genes accounted for more than 70% of identified pathogenic variants: PKD1 and PKD2 (n = 186, 53.4%), MUC1 (8.9%), and COL4A5 (8.3%). In 162 patients with a genetic diagnosis, excluding PKD1/PKD2, the a priori diagnosis was confirmed in 58% and in 13% the diagnosis was reclassified. A genetic diagnosis was established in 22 (29.7%) patients with CKD of uncertain aetiology. Based on genetic testing, a diagnostic kidney biopsy was unnecessary in 13 (8%) patients. Presence of family history of CKD and the underlying a priori diagnosis were independent predictors (P < 0.001) of a positive genetic diagnosis. Conclusions: A dedicated GKD clinic is a valuable resource, and its implementation of various genomic strategies has resulted in a direct, demonstrable clinical and therapeutic benefits to affected patients. Graphical abstract: [Figure not available: see fulltext.]

Original languageEnglish (US)
JournalJournal of Nephrology
DOIs
StateAccepted/In press - 2022

Keywords

  • Chronic kidney disease
  • Genetic kidney disease
  • Inherited kidney diseases
  • Next-generation sequencing
  • Polycystic kidney genetics

ASJC Scopus subject areas

  • Nephrology

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