Kidney Week

Abstract: FR-PO0148

Autosomal Dominant Tubulointerstitial Kidney Disease-Uromodulin (ADTKD-UMOD): The Irish Kidney Gene Project Experience

Session Information

• Hereditary Glomerular and Tubulointerstitial Kidney Diseases
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1202 Genetic Diseases of the Kidneys: Non-Cystic (Complex and Non-Cystic Monogenic)

Authors

• Rowan, Colm Anthony, Royal College of Surgeons in Ireland, Dublin, Leinster, Ireland

Colm Anthony Rowan

• Elhassan, Elhussein Aamir Elzein, Royal College of Surgeons in Ireland, Dublin, Leinster, Ireland

Elhussein Aamir Elzein Elhassan, MBBS, MS, MSc

• Clince, Michelle, Beaumont Hospital, Dublin, Leinster, Ireland

Michelle Clince, DrMed, MBChB

• Kmoch, Stanislav, Univerzita Karlova, Prague, Czechia

Stanislav Kmoch, MS, MSc, PhD

• Bleyer, Anthony J., Wake Forest University, Winston-Salem, North Carolina, United States

Anthony J. Bleyer, MD, MS, FASN

• Zivna, Martina, Univerzita Karlova, Prague, Czechia

Martina Zivna, MS, MSc, PhD

• Conlon, Peter J., Royal College of Surgeons in Ireland, Dublin, Leinster, Ireland

Peter J. Conlon, MBChB, FASN

Group or Team Name

• Irish Kidney Gene Project

Background

ADTKD is the 3^rd leading cause of genetic kidney disease. Due to the non-specific presentation, prevalence rates are under estimated. There is renewed interest in intermediate effect size variants with the now likely pathogenic UMOD-Tyr62Pro (T62P) variant. We sought to characterise and determine the prevalence of ADTKD-UMOD in Ireland.

Methods

The Irish kidney gene project examined all referrals to identify families with UMOD variants. We performed deep genetic (WES, MUC1 analysis and WGS) and phenotypic characterisation of this cohort.

Results

We identified 56 patients from 20 families with UMOD variants. 40 patients carried a UMOD-T62P variant and 16 canonical UMOD variants (UMOD-C). The prevalence is 11 per million which exceeds international prevalence rates. Including relatives who are clinically affected but not genotyped, the prevalence is 16 cases per million. The T62P variant was the only pathogenic variant in the UMOD-T62P group. The UMOD-T62P genotype presented at a significantly older age with significantly lower hyperuricaemia rates. Patients had a numerically higher eGFR at diagnosis compared to UMOD-C. The burden of hypertension and ESKD were comparable at 47.5% and 43.75% for UMOD-T62P and UMOD-C respectively. Functional analysis of UMOD-T62P demonstrated reduced urinary and serum uromodulin and reduced membrane translocation which was intermediate to that of UMOD-C and wild type UMOD.

Conclusion

ADTKD-UMOD is a significant contributor to ESKD accounting for 0.5% on dialysis in Ireland. UMOD-T62P was the largest contributor. Although delayed onset, the UMOD-T62P carries a significant burden of ESKD with rates comparable to UMOD-C variants. Functional analysis demonstrates intermediate damaging effect of the T62P variant.

Acknowledgment

I would like to acknowledge Dr Michelle Madden, Dr Daragh O'Donoghue for assistance in data collection, Dr Brian Pierce (Consutlant Histopathologist) for contribution with histological data and images and the Prague working group (Václav Janoušek, Petr Vyletal, Klára Svojšová, Katerina Hodanová, Alena Vrbacká, Zdislava Vaníčková, Jana Sovová, Jakub Kordík, Petr Novák) for their on going support in laboratory analysis of Uromodulin.

Funding

• Government Support – Non-U.S.