Clinical, pathological, and genetic variation characteristics of autosomal dominant tubulointerstitial kidney disease caused by UMOD gene mutation
10.3760/cma.j.cn441217-20241018-01026
- VernacularTitle:UMOD基因突变引起的常染色体显性遗传肾小管间质肾病的临床病理及基因变异特点分析
- Author:
Yu ZHOU
1
;
Xiaorong LIU
1
Author Information
1. 国家儿童医学中心 首都医科大学附属北京儿童医院肾内科，北京 100045
- Publication Type:Journal Article
- Keywords:
Genes, dominant;
Uromodulin;
Mutation;
Tubulointerstitial nephritis;
Hyperuricemia
- From:
Chinese Journal of Nephrology
2025;41(9):660-669
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To conduct a systematic review of reported cases of autosomal dominant tubulointerstitial kidney disease (ADTKD) caused by uromodulin ( UMOD) gene mutations (ADTKD- UMOD) in China, summarize the clinical, pathological and genetic variation characteristics, and analyze the genotype-phenotype correlation. Methods:It was a retrospective systematic analysis study. The search terms "UMOD", "ADTKD-UMOD", "uric acid kidney disease (UAKD)", "medullary cystic kidney disease type 2 (MCKD2)", and "familial juvenile hyperuricemic nephropathy type 1 (FJHN1)" were used, and relevant literature on ADTKD- UMOD cases in China were retrieved from PubMed, CNKI, Wanfang Data and Chinese Medical Journal Full-text Database. The data of the cases involved in the literature were collected and summarized, and the clinical and pathological characteristics and genetic variation features of Chinese ADTKD- UMOD patients were analyzed. The patients were divided into exon 3 mutation group and non-exon 3 mutation group based on the mutation sites, and the differences of clinical phenotypes between the two groups were compared. The patients were also divided into domain 8 cysteine (D8C) mutation group and non-D8C mutation group based on the mutation regions, and the differences of clinical phenotypes between the two groups were compared. Results:A total of 17 relevant articles on ADTKD- UMOD cases in China were retrieved, involving 57 patients from 34 families. The age at first diagnosis was 24.0 (20.0, 39.5) years. Fifty-three patients (93.0%) had a family history of nephropathy or hyperuricemia. Among the 48 patients with recorded blood uric acid levels, 36 patients (75.0%) had hyperuricemia, with age of 24.0 (20.3, 37.3) years. Fifty-four patients had chronic kidney disease assessment records, among which 46 patients (85.2%) developed chronic kidney disease, and 21 patients (38.9%) developed end-stage renal disease. The age of end-stage renal disease was 39.0 (24.0, 46.0) years, with age of 33.0 (21.0, 46.5) years in males and 39.5 (25.5, 45.5) years in females ( Z=-0.649, P=0.516). Twenty patients underwent renal biopsies, and 19/20 patients had tubular or interstitial lesions, and 9/20 patients had glomerular lesions, mainly manifested as focal segmental or global glomerulosclerosis. Forty patients had renal ultrasound examination records, among which 36 patients (90.0%) had abnormal results, with renal cysts being the most common type (12 patients, 30.0%). Among the 34 family cases, no ADTKD- UMOD hotspot mutation was found in the UMOD gene mutations. Thirty-two families (94.1%) were missense mutations, 26 families (76.5%) had mutation sites in exon 3, and 16 families (47.1%) had mutation regions in D8C. The proportion of hypertension in the non-exon 3 mutation group was higher than that in the exon 3 mutation group ( χ2=9.84, P=0.002). The proportion of males in the non-D8C mutation group was higher than that in the D8C mutation group ( χ2=4.97, P=0.026). Conclusions:The main clinical manifestations of Chinese ADTKD- UMOD patients are hyperuricemia, and the main renal histopathological changes are tubular and interstitial lesions. Some patients have glomerular lesions, which need to be differentiated from focal segmental glomerulosclerosis. Renal cysts detected by renal ultrasound can suggest the diagnosis of the disease. Missense mutation is the main type of UMOD gene mutations. The gene mutation region may be correlated with hypertension and gender.
