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.
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.
Am J Kidney Dis. 2018 Sep;72(3):411-418. doi: 10.1053/j.ajkd.2018.03.019. Epub 2018 May 18.
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.
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.
Hyperuricemia, ultrasound findings, renal histology, genetic mutations.
Age at ESRD, rate of decline in estimated glomerular filtration rate.
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/1.73m per year in the ADTKD-UMOD group versus -3.9mL/min/1.73m 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).
Relatively small Spanish cohort. MUC1 analysis limited to cytosine duplication.
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.
常染色体显性遗传性肾小管间质性肾病（ADTKD）是一种罕见的、诊断不足的终末期肾病（ESRD）病因。ADTKD 是由至少 4 种不同基因突变引起的：MUC1、UMOD、HNF1B 和 REN。
回顾性队列研究。
来自西班牙不同医院的 56 个家族（131 名受累个体）进行 ADTKD 转诊。收集临床、实验室、放射学和病理学数据，并对 UMOD、MUC1、REN 和 HNF1B 进行基因检测。
高尿酸血症、超声表现、肾脏组织学、基因突变。
ESRD 年龄、估算肾小球滤过率下降率。
25 个家族（45%）诊断为 ADTKD，9 个家族携带 UMOD 致病性变异（41 名受累成员），16 个家族携带 MUC1 致病性突变 c.(428)dupC（90 名受累成员）。在 REN 或 HNF1B 中未发现致病性变异。在 77 名发生 ESRD 的个体中，ADTKD-MUC1 组的 ESRD 发病中位年龄为 51 岁，ADTKD-UMOD 组为 56 岁（P=0.1）。携带 MUC1 重复的个体发生 ESRD 的风险更高（HR，2.24；P=0.03）。ADTKD-UMOD 组估算肾小球滤过率下降斜率为-3.0mL/min/1.73m/年，ADTKD-MUC1 组为-3.9mL/min/1.73m/年，两组间无显著差异（P=0.2）。ADTKD-UMOD 组高尿酸血症的患病率明显高于 ADTKD-MUC1 组（87%比 54%；P=0.006）。虽然该组更常发生痛风，但差异无统计学意义（24%比 7%；P=0.07）。
相对较小的西班牙队列。MUC1 分析仅限于胞嘧啶重复。
我们西班牙队列中 ADTKD 的主要遗传病因是 MUC1 致病性突变 c.(428)dupC。与 UMOD 突变相比，携带 MUC1 突变的个体肾脏存活率可能更差。临床表现无法区分这些变体。然而，ADTKD-UMOD 组中更常出现高尿酸血症和痛风。
