Investigating Modifier Genes in ADTKD-UMOD
Research type
Research Study
Full title
Investigating Modifier Genes in ADTKD-UMOD
IRAS ID
307369
Contact name
John Sayer
Contact email
Sponsor organisation
Newcastle upon Tyne Hospitals NHS Foundation Trust
Clinicaltrials.gov Identifier
NU-005414, MRC Funding No. ; NU-007132, Newcastle upon Tyne Hospitals NHS Charity Funding No.
Duration of Study in the UK
2 years, 9 months, 7 days
Research summary
Chronic kidney disease (CKD) is a major public health burden with limited treatments, poor outcomes, and high cost. At least 10% of adults progressing to end-stage kidney disease (ESKD) suffer from a monogenic disease. Mutations in the UMOD gene are the leading cause of autosomal dominant tubulointerstitial kidney disease (ADTKD). UMOD is kidney-specific and encodes Uromodulin, the most abundant protein in human urine and Uromodulin plays multiple physiological roles.
ADTKD-UMOD is estimated to be the most common monogenic kidney disease after autosomal dominant polycystic kidney disease and Alport syndrome. Apart from renal transplantation, no specific treatment is available. Median renal survival in ADTKD-UMOD is 54 years, with large interfamilial and intrafamilial variability ranging from late 20s to after 70 years suggesting that other genetic factors are regulating disease progression.
The genetic and environmental modifiers of ADTKD-UMOD disease progression are unknown and this study aims to find the factors which cause more severe disease and earlier onset kidney failure. This will enable us to find treatments for the first time in this disease (targeted at these genetic and environmental factors). This study also aims to determine possible biomarkers so that we can detect severe disease earlier than we would be able to see it using kidney function tests alone. This will enable us to target treatments much earlier in the disease when they become available.
Clinical/Genomic data will be made available via the National Registry of Rare Kidney Diseases (RaDaR). RaDaR was established and funded by the MRC, Kidney Research UK and Kidney Care UK in 2008 to develop cohorts of well-categorised patients for translational research. It rapidly captures a vast amount of real-time generic and disease-specific data using ‘Renal Patient View’ (national renal NHS-utilised database of all primary, secondary and tertiary care data) allowing for easy longitudinal deep phenotyping.
REC name
Yorkshire & The Humber - Leeds East Research Ethics Committee
REC reference
23/YH/0078
Date of REC Opinion
30 Mar 2023
REC opinion
Favourable Opinion