Uromodulin as a protein and genetic biomarker for hypertension: a detailed systematic review & meta-analysis

BackgroundHypertension (HTN) is a major global contributor to cardiovascular morbidity and mortality, and improved biomarkers are needed to better characterize individual risk, disease progression, and treatment response. Uromodulin (UMOD), the most abundant protein in human urine reflects tubular health and renal sodium handling. Genome-wide association studies (GWAS) have identified common UMOD promoter polymorphisms associated with HTN across diverse populations, sparking interest in UMOD as both a protein and genetic biomarker. We conducted a systematic review and meta-analysis to evaluate the diagnostic, prognostic, and predictive value of UMOD in HTN. MethodsWe conducted a systematic review and meta-analysis using PubMed and Embase. We included human and animal studies that evaluated UMOD protein level or UMOD-related GWAS outcomes in relation to HTN or HTN-related outcomes. Risk of bias was assessed using the Newcastle-Ottawa Scale. Inverse variance weighed random-effects models were used to analyze continuous outcomes. Publication bias was evaluated using Begg and Egger tests and funnel plots. ResultsForty studies met the inclusion criteria. Across diagnostic, prognostic, and predictive biomarker studies, 10,726 individuals with HTN and 8,762 normotensive (NTN) participants were included. Furthermore, there were 3,461 women with HTN and 3,605 NTN. GWAS studies included >450,000 HTN and >150,000 NTN individuals. Despite supportive findings from in vivo models, across diagnostic, prognostic, predictive, and GWAS qualitative and quantitative analyses, UMOD did not demonstrate clinically meaningful utility as a biomarker for HTN or HTN-related outcomes. ConclusionDespite strong biological plausibility linking UMOD to renal sodium handling and blood pressure regulation, our meta-analysis demonstrates that UMOD is not a clinically useful protein or genetic biomarker for HTN or HTN-related outcomes.