Autosomal Dominant Tubulointerstitial Kidney Disease: Clinical Presentation of Patients With ADTKD-UMOD and ADTKD-MUC1
Por:
Ayasreh, N, Bullich, G, Miquel, R, Furlano, M, Ruiz, P, Lorente, L, Valero, O, Garcia-Gonzalez, MA, Arhda, N, Garin, I, Martinez, V, Perez-Gomez, V, Fulladosa, X, Arroyo, D, Martinez-Vea, A, Espinosa, M, Ballarin, J, Ars, E, Torra, R
Publicada:
1 sep 2018
Resumen:
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 (-3.0 mL/min/1.73 m(2) per year in the ADTKD-UMOD group versus -3.9 mL/min/1.73 m(2) per year in the ADTKD-MUC1 group; P = 0.2). The prevalence of hyperuricemia was significantly higher in individuals with ADTKDUMOD (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.
Filiaciones:
Ayasreh, N:
Univ Autonoma Barcelona, IIB St Pau, Fdn Puigvert, Inherited Kidney Disorders,Nephrol Dept, Barcelona, Spain
Inst Invest Carlos III, REDinREN, Barcelona, Spain
Bullich, G:
Univ Autonoma Barcelona, IIB St Pau, Fdn Puigvert, Mol Biol Lab, Barcelona, Spain
Inst Invest Carlos III, REDinREN, Barcelona, Spain
Miquel, R:
Hosp Univ Canarias, Dept Nephrol, REDinREN, ISCIII, Tenerife, Spain
Furlano, M:
Univ Autonoma Barcelona, IIB St Pau, Fdn Puigvert, Inherited Kidney Disorders,Nephrol Dept, Barcelona, Spain
Inst Invest Carlos III, REDinREN, Barcelona, Spain
Ruiz, P:
Univ Autonoma Barcelona, IIB St Pau, Fdn Puigvert, Mol Biol Lab, Barcelona, Spain
Inst Invest Carlos III, REDinREN, Barcelona, Spain
Lorente, L:
Univ Autonoma Barcelona, IIB St Pau, Fdn Puigvert, Mol Biol Lab, Barcelona, Spain
Inst Invest Carlos III, REDinREN, Barcelona, Spain
Valero, O:
Univ Autonoma Barcelona, Serv Estadist Aplicada, Barcelona, Spain
Garcia-Gonzalez, MA:
Inst Invest Carlos III, REDinREN, Barcelona, Spain
Complexo Hosp Santiago de Compostela CHUS, Inst Invest Sanitaria IDIS, Lab Nefrol, Grp Genet & Biol Desarrollo Enfermedades Renales, Santiago De Compostela, Spain
Arhda, N:
Complexo Hosp Santiago de Compostela CHUS, Inst Invest Sanitaria IDIS, Lab Nefrol, Grp Genet & Biol Desarrollo Enfermedades Renales, Santiago De Compostela, Spain
Garin, I:
Hosp Univ, OSI Araba, Lab Epi Genet Mol, Vitoria, Spain
Martinez, V:
Univ Virgen de la Arrixaca, Hosp Clin, Dept Nephrol, El Palmar, Murcia, Spain
Perez-Gomez, V:
Inst Invest Carlos III, REDinREN, Barcelona, Spain
Fdn Jimenez Diaz, Univ Hosp, Dept Nephrol, IIS, Madrid, Spain
Fulladosa, X:
Inst Invest Carlos III, REDinREN, Barcelona, Spain
Hosp Univ Bellvitge, IDIBELL, Dept Nephrol, Barcelona, Spain
Arroyo, D:
Inst Invest Carlos III, REDinREN, Barcelona, Spain
Vasc & Renal Translat Res Grp, Lleida, Spain
Martinez-Vea, A:
Hosp Univ Joan XXIII, Dept Nephrol, Tarragona, Spain
Espinosa, M:
Inst Invest Carlos III, REDinREN, Barcelona, Spain
Hosp Univ Reina Sofia, Cordoba, Spain
Ballarin, J:
Univ Autonoma Barcelona, IIB St Pau, Fdn Puigvert, Inherited Kidney Disorders,Nephrol Dept, Barcelona, Spain
Inst Invest Carlos III, REDinREN, Barcelona, Spain
Ars, E:
Univ Autonoma Barcelona, IIB St Pau, Fdn Puigvert, Mol Biol Lab, Barcelona, Spain
Inst Invest Carlos III, REDinREN, Barcelona, Spain
Torra, R:
Univ Autonoma Barcelona, IIB St Pau, Fdn Puigvert, Inherited Kidney Disorders,Nephrol Dept, Barcelona, Spain
Inst Invest Carlos III, REDinREN, Barcelona, Spain
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