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

摘要

Rationale & ObjectiveAutosomal 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, andREN. Study DesignRetrospective cohort study. Setting & Participants56 families (131 affected individuals) with ADTKD referred from different Spanish hospitals. Clinical, laboratory, radiologic, and pathologic data were collected, and genetic testing forUMOD,MUC1,REN, andHNF1Bwas performed. PredictorsHyperuricemia, ultrasound findings, renal histology, genetic mutations. OutcomesAge at ESRD, rate of decline in estimated glomerular filtration rate. ResultsADTKD was diagnosed in 25 families (45%), 9 carriedUMODpathogenic variants (41 affected members), and 16 carried theMUC1pathogenic mutation c.(428)dupC (90 affected members). No pathogenic variants were identified inRENorHNF1B. Among the 77 individuals who developed ESRD, median age at onset of ESRD was 51 years for those with ADTKD-MUC1versus 56 years (P=0.1) for those with ADTKD-UMOD. Individuals with theMUC1duplication 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/1.73m2per year in the ADTKD-UMODgroup versus??3.9mL/min/1.73m2per year in the ADTKD-MUC1group;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). LimitationsRelatively small Spanish cohort.MUC1analysis limited to cytosine duplication. ConclusionsThe main genetic cause of ADTKD in our Spanish cohort is theMUC1pathogenic mutation c.(428)dupC. Renal survival may be worse in individuals with theMUC1mutation than in those withUMODmutations. Clinical presentation does not permit distinguishing between these variants. However, hyperuricemia and gout are more frequent in individuals with ADTKD-UMOD.