TY - JOUR
T1 - The utility of a genetic kidney disease clinic employing a broad range of genomic testing platforms
T2 - experience of the Irish Kidney Gene Project
AU - Elhassan, Elhussein A.E.
AU - Murray, Susan L.
AU - Connaughton, Dervla M.
AU - Kennedy, Claire
AU - Cormican, Sarah
AU - Cowhig, Cliona
AU - Stapleton, Caragh
AU - Little, Mark A.
AU - Kidd, Kendrah
AU - Bleyer, Anthony J.
AU - Živná, Martina
AU - Kmoch, Stanislav
AU - Fennelly, Neil K.
AU - Doyle, Brendan
AU - Dorman, Anthony
AU - Griffin, Matthew D.
AU - Casserly, Liam
AU - Harris, Peter C.
AU - Hildebrandt, Friedhelm
AU - Cavalleri, Gianpiero L.
AU - Benson, Katherine A.
AU - Conlon, Peter J.
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/7
Y1 - 2022/7
N2 - 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.]
AB - 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.]
KW - Chronic kidney disease
KW - Genetic kidney disease
KW - Inherited kidney diseases
KW - Next-generation sequencing
KW - Polycystic kidney genetics
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U2 - 10.1007/s40620-021-01236-2
DO - 10.1007/s40620-021-01236-2
M3 - Article
C2 - 35099770
AN - SCOPUS:85123930814
SN - 1121-8428
VL - 35
SP - 1655
EP - 1665
JO - Journal of Nephrology
JF - Journal of Nephrology
IS - 6
ER -