Format

Send to

Choose Destination
Am J Kidney Dis. 2018 Sep;72(3):411-418. doi: 10.1053/j.ajkd.2018.03.019. Epub 2018 May 18.

Autosomal Dominant Tubulointerstitial Kidney Disease: Clinical Presentation of Patients With ADTKD-UMOD and ADTKD-MUC1.

Author information

1
Inherited Kidney Disorders, Nephrology Department, Fundació Puigvert, Instituto de Investigaciones Biomédicas Sant Pau (IIB-Sant Pau), Universitat Autònoma de Barcelona, Barcelona; REDinREN, Instituto de Investigación Carlos III, Barcelona.
2
Molecular Biology Laboratory, Fundació Puigvert, Instituto de Investigaciones Biomédicas Sant Pau (IIB-Sant Pau), Universitat Autònoma de Barcelona, Barcelona; REDinREN, Instituto de Investigación Carlos III, Barcelona.
3
Nephrology Department, Hospital Universitario de Canarias, Tenerife, REDinREN, ISCIII.
4
Servei d'Estadística Aplicada, Universitat Autònoma de Barcelona.
5
REDinREN, Instituto de Investigación Carlos III, Barcelona; Complexo Hospitalario de Santiago de Compostela (CHUS), Instituto de Investigación Sanitaria (IDIS) Laboratorio de Nefrología, Grupo de Genética y Biología del Desarrollo de las Enfermedades Renales.
6
Complexo Hospitalario de Santiago de Compostela (CHUS), Instituto de Investigación Sanitaria (IDIS) Laboratorio de Nefrología, Grupo de Genética y Biología del Desarrollo de las Enfermedades Renales.
7
Laboratorio de (Epi)Genética Molecular, OSI Araba, Hospital Universitario, Vitoria-Gasteiz.
8
Nephrology Department, Hospital Clínico Universitario Virgen de la Arrixaca (Murcia).
9
REDinREN, Instituto de Investigación Carlos III, Barcelona; Nephrology Department, Hospital Universitario Fundación Jiménez Díaz, IIS Fundación Jiménez Díaz.
10
REDinREN, Instituto de Investigación Carlos III, Barcelona; Nephrology Department, Hospital Universitari de Bellvitge-IDIBELL, L'Hospitalet, Barcelona.
11
REDinREN, Instituto de Investigación Carlos III, Barcelona; Vascular and Renal Translational Research Group, IRB Lleida.
12
Nephrology Department, Hospital Universitari Joan XXIII, Tarragona, Spain.
13
REDinREN, Instituto de Investigación Carlos III, Barcelona; Hospital Universitario Reina Sofía, Córdoba, Spain.
14
Inherited Kidney Disorders, Nephrology Department, Fundació Puigvert, Instituto de Investigaciones Biomédicas Sant Pau (IIB-Sant Pau), Universitat Autònoma de Barcelona, Barcelona; REDinREN, Instituto de Investigación Carlos III, Barcelona. Electronic address: rtorra@fundacio-puigvert.es.

Abstract

RATIONALE & OBJECTIVE:

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare underdiagnosed cause of end-stage renal disease (ESRD). ADTKD is caused by mutations in at least 4 different genes: MUC1, UMOD, HNF1B, and REN.

STUDY DESIGN:

Retrospective cohort study.

SETTING & PARTICIPANTS:

56 families (131 affected individuals) with ADTKD referred from different Spanish hospitals. Clinical, laboratory, radiologic, and pathologic data were collected, and genetic testing for UMOD, MUC1, REN, and HNF1B was performed.

PREDICTORS:

Hyperuricemia, ultrasound findings, renal histology, genetic mutations.

OUTCOMES:

Age at ESRD, rate of decline in estimated glomerular filtration rate.

RESULTS:

ADTKD was diagnosed in 25 families (45%), 9 carried UMOD pathogenic variants (41 affected members), and 16 carried the MUC1 pathogenic mutation c.(428)dupC (90 affected members). No pathogenic variants were identified in REN or HNF1B. Among the 77 individuals who developed ESRD, median age at onset of ESRD was 51 years for those with ADTKD-MUC1 versus 56 years (P=0.1) for those with ADTKD-UMOD. Individuals with the MUC1 duplication presented higher risk for developing ESRD (HR, 2.24; P=0.03). The slope of decline in estimated glomerular filtration rate showed no significant difference between groups (-3.0mL/min/1.73m2 per year in the ADTKD-UMOD group versus -3.9mL/min/1.73m2 per year in the ADTKD-MUC1 group; P=0.2). The prevalence of hyperuricemia was significantly higher in individuals with ADTKD-UMOD (87% vs 54%; P=0.006). Although gout occurred more frequently in this group, the difference was not statistically significant (24% vs 7%; P=0.07).

LIMITATIONS:

Relatively small Spanish cohort. MUC1 analysis limited to cytosine duplication.

CONCLUSIONS:

The main genetic cause of ADTKD in our Spanish cohort is the MUC1 pathogenic mutation c.(428)dupC. Renal survival may be worse in individuals with the MUC1 mutation than in those with UMOD mutations. Clinical presentation does not permit distinguishing between these variants. However, hyperuricemia and gout are more frequent in individuals with ADTKD-UMOD.

KEYWORDS:

Autosomal dominant tubulointerstitial kidney disease (ADTKD); MUC1; SNaPshot; UMOD; clinical presentation; genetic testing; gout; hyperuricemia; inherited kidney disease; intrafamilial variation; kidney failure; kidney function decline; pedigree

PMID:
29784615
DOI:
10.1053/j.ajkd.2018.03.019

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center