Case Report: Uromodulin-associated autosomal dominant tubulointerstitial kidney disease: case analysis and literature review

Autosomal dominant tubulointerstitial kidney disease caused by UMOD variants (ADTKD-UMOD) is a rare hereditary disorder characterized by early-onset hyperuricemia, gout, and progressive kidney dysfunction. Diagnosis is established by genetic testing. We report the case of a 25-year-old man who presented with elevated serum creatinine (Scr) and uric acid (UA) levels. His father and elder sister had chronic kidney disease of unknown etiology, suggesting an autosomal dominant inheritance pattern. A comprehensive evaluation excluded secondary causes of hyperuricemia and kidney dysfunction. Genetic testing identified a novel heterozygous missense variant, UMOD (NM_003361.4): c.274T>A (p.Cys92Ser), in exon 3 of the gene. The same variant was also detected in affected relatives. In silico analyses predicted a deleterious effect, and the variant was classified as likely pathogenic according to the ACMG/AMP criteria (PM5_Moderate, PP3_Moderate, PM2_Supporting). During longitudinal follow-up with febuxostat treatment, serum urate levels decreased, while progressive deterioration of renal function was observed during the observational period. By analogy to well-characterized pathogenic cysteine-altering UMOD variants, we hypothesize that p.Cys92Ser may promote uromodulin misfolding and endoplasmic reticulum retention and thereby contribute to kidney injury; this mechanistic inference remains to be verified by direct functional experiments for this novel variant. This report expands the mutational spectrum of ADTKD-UMOD and underscores the importance of early genetic testing in at-risk families, as well as standardized long-term follow-up and management for this progressive disorder.