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Abstract: FR-PO809

Prevalence and Clinical Features of ADTKD-UMOD in Hemodialysis Patients in a Geo-Referenced Population in Southeastern Brazil: The REGENT Study

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Reis Almeida, Jorge, Federal Fluminense University, Niteroi, Brazil
  • Abreu, Cinthia Da costa, Federal Fluminense University, Niteroi, Brazil
  • Souza, Cintia, Federal Fluminense University, Niteroi, Brazil
  • Lopes, Ludiana, Federal Fluminense University, Niteroi, Brazil
  • Cavalcanti, Ohanna, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil
  • Kehdy, Fernanda, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil
  • Vyletal, Petr, 1st Faculty of Medicine UK and VFN in Prague, Department of Pediatrics and Adolescent Medicine, Diagnostic and Research Unit for Rare Diseases, Prague, Czechia
  • Kmoch, Stanislav, 1st Faculty of Medicine UK and VFN in Prague, Department of Pediatrics and Adolescent Medicine, Diagnostic and Research Unit for Rare Diseases, Prague, Czechia
  • 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
Background

Autosomal dominant tubulointerstitial kidney disease due to UMOD mutations (ADTKD-UMOD) is a rare genetic kidney disease whose prevalence is not well known. We studied the prevalence and clinical aspects of ADTKD-UMOD in hemodialysis (HD) patients in a metropolitan health region of Southeastern Brazil (Metro-II).

Methods

The REGENT study (Familiar Renal Disease, Epidemiology and Genetics in Niteroi) was designed to study familial renal diseases in Metro-II (2 million inhabitants). Between 2017/2018, we evaluated HD patients geo-referenced in Metro-II. Each patient was asked whether any other family members had developed ESRD. If affirmative, after clinical exclusion of other known diseases (such as ADPKD, Fabry's, Alport's, Familial glomerulonephritis, etc.), blood was collected for UMOD genetic analysis.

Results

209 of 1308 patients (16%) indicated a family history of kidney disease. After exclusions, 70 remained as index cases of an unknown familial disease (5.4% of the total). These patients reached ESRD at a younger age (p < 0.05), did outpatient treatment before dialysis (p < 0.001), and were on dialysis for more years (p < 0.01). Family pedigrees showed a dominant pattern in 35%. Three of the index cases were found to have unique UMOD variants, consisting of 3 heterozygous missense mutations (c.163 G>A; p.Gly55Ser) (c.667 T>G; p.Cis223Gly) and (c.263 G>A; p.Gly88Asp). The first family consisted of 3 HD, 1 CAPD, 1 transplant and 2 outpatients. Genotyping in the 3 families revealed a total of 18 UMOD affected individuals, regardless of HD, age or symptoms. Metro-II calculated prevalence was 10 ppm. Juvenile gout was not present, simple cysts were present in a few cases. There was no proteinuria or hematuria. Some cases showed hyperuricemia, episodes of urinary tract infection, anemia in childhood and a history of hypothyroidism without specific antibodies. Patients started HD on average between 51.7±9.4 years. A decline in eGFR first occurred between 32.7±4.4 years. Renal biopsy in 3 patients revealed interstitial nephritis.

Conclusion

Familial renal disease without diagnosis constitutes a significant proportion of ESRD patients in Brazil. ADTKD is rare, but frequently underdiagnosed.

Funding

  • Government Support - Non-U.S.