Autosomal dominant tubulointerstitial kidney disease ADTKD in Ireland.pdf (1.35 MB)
Autosomal dominant tubulointerstitial kidney disease (ADTKD) in Ireland
journal contributionposted on 2021-04-23, 16:38 authored by Sarah Cormican, DM Connaughton, Claire Kennedy, Susan Murray, M Živná, S Kmoch, Neil K. Fennelly, P O’Kelly, Katherine BensonKatherine Benson, ET Conlon, Gianpiero CavalleriGianpiero Cavalleri, Claire FoleyClaire Foley, B Doyle, Tony DormanTony Dorman, MA Little, P Lavin, K Kidd, AJ Bleyer, Peter ConlonPeter Conlon
Introduction: Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare genetic cause of renal impairment resulting from mutations in the MUC1, UMOD, HNF1B, REN, and SEC61A1 genes. Neither the national or global prevalence of these diseases has been determined. We aimed to establish a database of patients with ADTKD in Ireland and report the clinical and genetic characteristics of these families.
Methods: We identified patients via the Irish Kidney Gene Project and referral to the national renal genetics clinic in Beaumont Hospital who met the clinical criteria for ADTKD (chronic kidney disease, bland urinary sediment, and autosomal dominant inheritance). Eligible patients were then invited to undergo genetic testing by a variety of methods including panel-based testing, whole exome sequencing and, in five families who met the criteria for diagnosis of ADTKD but were negative for causal genetic mutations, we analyzed urinary cell smears for the presence of MUC1fs protein.
Results: We studied 54 individuals from 16 families. We identified mutations in the MUC1 gene in three families, UMOD in five families, HNF1beta in two families, and the presence of abnormal MUC1 protein in urine smears in three families (one of which was previously known to carry the genetic mutation). We were unable to identify a mutation in 4 families (3 of whom also tested negative for urinary MUC1fs).
Conclusions: There are 4443 people with ESRD in Ireland, 24 of whom are members of the cohort described herein. We observe that ADTKD represents at least 0.54% of Irish ESRD patients.
Punchestown Kidney Research Fund
Beaumont Nephrology Research Fund
Meath Foundation grant [Grant no.:205229.13987]
Science Foundation Ireland (SFI) grant [Grant number: 11/Y/B2093]
Irish Clinical Academic Training (ICAT) Programme
Health Research Board Ireland [Grant Numbers 203930/B/16/Z and HPF-206–674].
International Pediatric Research Foundation Early Investigators’ Exchange Program
Amgen Irish Nephrology Society Specialist Registrar Research Bursary
Ministry of Health of the Czech Republic [grant NV17-29786A]
Charles Universityin Prague institutional programs [UNCE/MED/007 and PROGRES-Q26/LF1]
CommentsThe original article can be found on https://www.tandfonline.com/
Published CitationCormican S, Connaughton DM, Kennedy C, Murray S, Živná M, Kmoch S, Fennelly NK, O’Kelly P, Benson KA, Conlon ET, Cavalleri G, Foley C, Doyle B, Dorman A, Little MA, Lavin P, Kidd K, Bleyer AJ, Conlon PJ. Autosomal dominant tubulointerstitial kidney disease (ADTKD) in Ireland. Renal Failure. 2019;41(1):832-841.
Publication Date11 September 2019
- Beaumont Hospital
- Clinical Research Centre
- School of Pharmacy and Biomolecular Sciences
- Neurological and Psychiatric Disorders
- Vascular Biology
PublisherInforma UK Limited
- Published Version (Version of Record)