Abstract: FR-PO327

The Burden of Autosomal Dominant Tubulo-Interstitial Kidney Disease (ADTKD) in Ireland

Session Information

Category: Genetic Diseases of the Kidney

  • 801 Cystic Kidney Diseases

Authors

  • Cormican, Sarah, Beaumont Hospital, Dublin 9, Ireland
  • Kidd, Kendrah O., Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States
  • Bleyer, Anthony J., Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States
  • Conlon, Peter J., Beaumont Hospital, Dublin 9, Co Dublin, Ireland
  • Connaughton, Dervla M., Boston Children's Hospital, Boston, Massachusetts, United States
  • Kennedy, Claire, None, Dublin 9, Ireland
  • Benson, Katherine A., Queen's University, Belfast, Belfast, United Kingdom
  • Cavalleri, Gianpiero, RCSI, Dublin, Italy
  • Doyle, Brendan, Beaumont Hospital, Dublin 9, Ireland
  • Dorman, Anthony M., Beaumont Hospital, Dublin 9, Ireland
  • Little, Mark Alan, Trinity College Dublin, Dublin, Ireland
  • Lavin, Peter J., Trinity College Dublin, Dublin, Ireland
Background

Hereditary mutations in the MUC-1, UMOD, HNF and REN-1 genes cause renal tubular atrophy, interstitial inflammation and fibrosis with progressive renal impairment. A recent KDIGO consensus report advocated the unified term ADTKD (sub-classified by causative gene) for these conditions, replacing older terminology such as medullary cystic kidney disease.

Methods

Individuals with possible ADTKD were identified by the Irish Kidney Gene Project and invited to attend for DNA collection with the Rare Kidney Disease Registry and Biobank. Genetic analysis was undertaken in RCSI Renal Genetics Unit and the Nephrology Department in the Wake Forest School of Medicine. Patients were sub-categorised as ADTKD-MUC1, ADTKD-UMOD or ADTKD-NOS (not otherwise specified) based on the identification of a mutation in the patient or an affected relative.

Results

64 individuals from 28 families were included. Genotyping results are available on 36 individuals from 22 families. Native kidney biopsy results were available for 32 patients.

19 patients from 3 families were categorised as ADTKD-MUC, 14 from 3 families were categorised as ADTKD-UMOD. 31 patients with clinical features of ADTKD met criteria for inclusion based on family history and renal biopsy findings. 18 have been tested without identified mutation, 4 have passed away and genetic material is not available. Details of genetic testing and clinical features are shown in Table 1. 40% of patients were hypertensive at presentation. Significant proteinuria occurred in 3/30 individuals with available. 26 patients with confirmed or suspected ADTKD have reached ESRD.

Conclusion

ADTKD accounts for approx. 0.06% of Irish cases of ESRD. Significant progress has been made in identifying causative mutations. Clinical awareness of ADTKD enables screening of relatives and early diagnosis.

Table 1
 UMOD (n=14)MUC-1 (n=19)ADTKD-NOS (n=31)p-value
Confirmed Mutation (n) / Tested (n)7/710/110/18NA
Number of Families3322NA
Mean Age at Presentation (years)4336410.66
Mean Creatinine at Presentation2671352710.012
Mean Age at ESRD (years)5344440.34
Gout (%)86%0%31%<0.0001
% Fibrosis on Biopsy (mean)60%74%63%Insufficient Data