Clinical and genetic spectra of autosomal dominant tubulointerstitial kidney disease due to mutations in UMOD and MUC1

Eric Olinger, Patrick Hofmann, Kendrah Kidd, Inès Dufour, Hendrica Belge, Céline Schaeffer, Anne Kipp, Olivier Bonny, Constantinos Deltas, Nathalie Demoulin, Thomas Fehr, Daniel G. Fuster, Daniel P. Gale, Eric Goffin, Kateřina Hodaňová, Uyen Huynh-Do, Andreas Kistler, Johann Morelle, Gregory Papagregoriou, Yves PirsonRichard Sandford, John A. Sayer, Roser Torra, Christina Venzin, Reto Venzin, Bruno Vogt, Martina Živná, Anna Greka, Karin Dahan, Luca Rampoldi, Stanislav Kmoch, Anthony J. Bleyer, Olivier Devuyst

Research output: Contribution to journalArticlepeer-review


Autosomal dominant tubulointerstitial kidney disease (ADTKD) is an increasingly recognized cause of end-stage kidney disease, primarily due to mutations in UMOD and MUC1. The lack of clinical recognition and the small size of cohorts have slowed the understanding of disease ontology and development of diagnostic algorithms. We analyzed two registries from Europe and the United States to define genetic and clinical characteristics of ADTKD-UMOD and ADTKD-MUC1 and develop a practical score to guide genetic testing. Our study encompassed 726 patients from 585 families with a presumptive diagnosis of ADTKD along with clinical, biochemical, genetic and radiologic data. Collectively, 106 different UMOD mutations were detected in 216/562 (38.4%) of families with ADTKD (303 patients), and 4 different MUC1 mutations in 72/205 (35.1%) of the families that are UMOD-negative (83 patients). The median kidney survival was significantly shorter in patients with ADTKD-MUC1 compared to ADTKD-UMOD (46 vs. 54 years, respectively), whereas the median gout-free survival was dramatically reduced in patients with ADTKD-UMOD compared to ADTKD-MUC1 (30 vs. 67 years, respectively). In contrast to patients with ADTKD-UMOD, patients with ADTKD-MUC1 had normal urinary excretion of uromodulin and distribution of uromodulin in tubular cells. A diagnostic algorithm based on a simple score coupled with urinary uromodulin measurements separated patients with ADTKD-UMOD from those with ADTKD-MUC1 with a sensitivity of 94.1%, a specificity of 74.3% and a positive predictive value of 84.2% for a UMOD mutation. Thus, ADTKD-UMOD is more frequently diagnosed than ADTKD-MUC1, ADTKD subtypes present with distinct clinical features, and a simple score coupled with urine uromodulin measurements may help prioritizing genetic testing.

Original languageEnglish
Pages (from-to)717-731
Number of pages15
JournalKidney International
Issue number3
Publication statusPublished - Sep 2020


  • diagnostic score
  • dominant kidney disease
  • gout
  • mucin-1
  • uromodulin

ASJC Scopus subject areas

  • Nephrology


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