Clinical and genetic spectra of autosomal dominant tubulointerstitial kidney disease due to mutations in UMOD and MUC1
Olinger, Eric (Newcastle University)
Hofmann, Patrick (Hospital Uster)
Kidd, Kendrah (Charles University)
Dufour, Inès (Division of Nephrology. Cliniques Universitaires Saint-Luc)
Belge, Hendrica (Institute of Pathology and Genetics)
Schaeffer, Céline (San Raffaele Scientific Institute)
Kipp, Anne (University of Zurich)
Bonny, Olivier (Lausanne University Hospital)
Deltas, Constantinos (University of Cyprus)
Demoulin, Nathalie (Université catholique de Louvain)
Fehr, Thomas (Cantonal Hospital Graubuenden)
Fuster, Daniel G. (Inselspital Bern University Hospital)
Gale, Daniel (University College of London)
Goffin, Eric (Université catholique de Louvain)
Hodaňová, Kateřina (Charles University)
Huynh-Do, Uyen (Inselspital Bern University Hospital)
Kistler, Andreas (Cantonal Hospital Frauenfeld)
Morelle, Johann (Université catholique de Louvain)
Papagregoriou, Gregory (University of Cyprus)
Pirson, Yves (Cliniques Universitaires Saint-Luc)
Sandford, Richard (Cambridge Biomedical Campus)
Sayer, John (Newcastle University)
Torra Balcells, Roser (Institut d'Investigació Biomèdica Sant Pau)
Venzin, Christina (Hospital Davos)
Venzin, Reto (Cantonal Hospital Graubuenden)
Vogt, Bruno (Inselspital Bern University Hospital)
Živná, Martina (Charles University)
Greka, Anna (Massachusetts Institute of Technology)
Dahan, Karin (Institute of Pathology and Genetics)
Rampoldi, Luca (San Raffaele Scientific Institute)
Kmoch, Stanislav (Charles University)
Bleyer, Anthony (Charles University)
Devuyst, Olivier (Cliniques Universitaires Saint-Luc)
Universitat Autònoma de Barcelona

Date:	2020
Abstract:	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.
Grants:	Ministerio de Economía y Competitividad PI15/01824 Instituto de Salud Carlos III PI18/00362
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Diagnostic score ; Dominant kidney disease ; Gout ; Mucin-1 ; Uromodulin
Published in:	Kidney International, Vol. 98 Núm. 3 (september 2020) , p. 717-731, ISSN 1523-1755

DOI: 10.1016/j.kint.2020.04.038
PMID: 32450155

15 p, 1.9 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
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