Case Report: UMOD gene mutation and phenotypic overlap with REN in autosomal dominant tubulointerstitial kidney disease

Sep 28, 2026

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare monogenic kidney disorder marked by progressive tubular atrophy and interstitial fibrosis, commonly linked to pathogenic variants in UMOD, REN, MUC1, and HNF1B. This case report describes a Chinese patient with ADTKD-UMOD carrying a heterozygous missense UMOD mutation, presenting classic UMOD findings such as hyperuricemia and gout alongside atypical REN-associated endocrine and metabolic abnormalities, including anemia, hypotension, and hyporeninemic hypoaldosteronism. Renal biopsy and genetic testing ultimately confirmed the UMOD-driven ADTKD diagnosis.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages6

Reading Time15 min

AccessFree to download

1 Introduction

2 Case presentation

2.1 Clinical and laboratory findings

TYPE Case Report PUBLISHED 18 December 2025 DOI 10.3389/fgene.2025.1661377 OPEN ACCESS EDITED BY Longshan Liu, First Affiliated Hospital of Sun Yat-sen University, China REVIEWED BY Marcelo De Sousa Tavares, Grupo Santa Casa BH, Brazil Manuel Lopez Mendoza, Virgen del Rocío University Hospital, Spain *CORRESPONDENCE Xianfa Li, [lixianfa025@163.com](lixianfa025@163.com)[ ](lixianfa025@163.com)Dongrong Yu, [yudr68@163.com](yudr68@163.com)[ ](yudr68@163.com)RECEIVED 07 July 2025 REVISED 21 November 2025 ACCEPTED 02 December 2025 PUBLISHED 18 December 2025 CITATION Xu J, Chen E, Shi W, He W, Yu D and Li X (2025) Case Report: UMOD gene mutation and phenotypic overlap with REN in autosomal dominant tubulointerstitial kidney disease. Front. Genet. 16:1661377 . doi: 10.3389/fgene.2025.1661377 COPYRIGHT © 2025 Xu, Chen, Shi, He, Yu and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Case Report: UMOD gene mutation and phenotypic overlap with REN in autosomal dominant tubulointerstitial kidney disease Jingying Xu 1,2, Enhui Chen 1,2, Wen Shi 1,2, Wenhui He 1,2, Dongrong Yu 2* and Xianfa Li 2* 1Department of Nephrology, Zhejiang Chinese Medical University, Hangzhou, China, 2Department of Nephrology, Hangzhou TCM Hospital of Zhejiang Chinese Medical University (Hangzhou Hospital of Traditional Chinese Medicine), Hangzhou, China Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare monogenic kidney disorder characterized by progressive tubular atrophy and interstitial fibrosis. It is primarily associated with pathogenic variants in genes such as UMOD (uromodulin), REN (renin), MUC1 (mucin 1), and HNF1B (hepatocyte nuclear factor 1-beta) . We report a unique Chinese case of ADTKD-UMOD in a patient carrying a UMOD gene mutation. The clinical presentation was complex: in addition to the classic features of UMOD mutations (hyperuricemia and gout), the patient exhibited endocrine and metabolic abnormalities typically linked to REN gene defects (ADTKD-REN), including anemia, hypotension, and hyporeninemic hypoaldosteronism. However, renal biopsy and genetic testing ultimately confirmed the diagnosis as ADTKD caused by a heterozygous missense mutation in UMOD gene. KEYWORDS ADTKD, tubulointerstitial injury, gene mutation, UMOD, REN 1 Introduction ADTKD (autosomal dominant tubulointerstitial kidney disease) (Eckardt et al., 2015) represents a group of monogenic hereditary kidney disorders characterized by progressive tubulointerstitial damage. It constitutes one of the significant genetic etiologies for endstage renal disease (ESRD) . The clinical phenotype demonstrates high heterogeneity. During early stages, due to insidious clinical manifestations and the absence of specific biomarkers (e.g., urine sediment examination often shows no significant abnormalities), coupled with typically inconspicuous pathological alterations, it is frequently misdiagnosed as chronic kidney disease of unknown etiology. Recent advancements in whole-exome sequencing have significantly improved molecular diagnostic rates for ADTKD. Currently identified pathogenic genes include UMOD (uromodulin gene), REN (renin gene), MUC1 (mucin 1 gene), and HNF1B (hepatocyte nuclear factor 1β gene) (Bolar et al., 2016). Among these, UMOD was the first identified causative gene (ADTKD-UMOD) . Its mutations exert dominant-negative effects, leading to abnormal accumulation of misfolded uromodulin in the endoplasmic reticulum of thick ascending limb epithelial cells. This subsequently triggers endoplasmic reticulum stres

FAQs

What is ADTKD and which genes are commonly involved?

ADTKD is a rare monogenic kidney disorder with progressive tubular atrophy and interstitial fibrosis. It is primarily associated with pathogenic variants in UMOD, REN, MUC1, and HNF1B.

What were the key clinical features in this reported case?

The patient had persistent hyperuricemia and developed gout, along with endocrine and metabolic abnormalities typical of REN defects, including anemia and hypotension with hyporeninemic hypoaldosteronism.

How was the final diagnosis confirmed?

Renal biopsy and genetic testing confirmed ADTKD caused by a heterozygous missense mutation in the UMOD gene.

Sep 28, 2026

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