부산대학교 도서관

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is an increasingly recognized cause of end-stage kidney disease, primarily due to mutations in UMODand 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-UMODand ADTKD-MUC1and 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 UMODmutations were detected in 216/562 (38.4%) of families with ADTKD (303 patients), and 4 different MUC1mutations 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-MUC1compared to ADTKD-UMOD(46 vs. 54 years, respectively), whereas the median gout-free survival was dramatically reduced in patients with ADTKD-UMODcompared to ADTKD-MUC1(30 vs. 67 years, respectively). In contrast to patients with ADTKD-UMOD, patients with ADTKD-MUC1had 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-UMODfrom those with ADTKD-MUC1with a sensitivity of 94.1%, a specificity of 74.3% and a positive predictive value of 84.2% for a UMODmutation. Thus, ADTKD-UMODis 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.