Uromodulin did not demonstrate clinically meaningful utility as a protein or genetic biomarker for hypertension across 35 studies involving over 450,000 hypertensive individuals.
Does uromodulin serve as a clinically useful protein or genetic biomarker for hypertension?
Uromodulin is not a clinically useful protein or genetic biomarker for hypertension, despite its role in renal sodium handling.
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Background: Hypertension is a major global cause of cardiovascular morbidity and mortality, and improved biomarkers are needed to assess risk, disease progression, and treatment response.Uromodulin reflects tubular health and renal sodium handling and has been linked to hypertension.We performed a systematic review and meta-analysis to evaluate uromodulin as a biomarker for hypertension. Methods:We included human studies evaluating uromodulin protein levels or uromodulinrelated genome-wide association study outcomes in relation to hypertension.Continuous outcomes were analyzed using inverse variance weighted random effects models, and publication bias was assessed with Begg, Egger tests and funnel plots. Results:Thirty-five studies met the inclusion criteria.Across diagnostic, prognostic, and predictive biomarker studies, 10,726 individuals with hypertension (3,461 females) and 8,762 (3,605 females).Genome-wide association studies included >450,000 hypertension and >150,000 normotensive Across all analyses, uromodulin did not demonstrate clinically meaningful utility as a biomarker for hypertension or hypertension-related outcomes. Conclusion:Our meta-analysis shows that uromodulin is not a clinically useful protein or genetic biomarker for hypertension or hypertension-related outcomes.However, it may still have potential utility in predicting other cardiovascular outcomes.Across the diagnostic, prognostic, and predictive studies, a total of 10,726 (3,461 females) individuals with hypertension and 8,762 (3,605 females) normotensives were evaluated.The majority of these studies focused on essential hypertension, while six studies examined chronic kidney disease-hypertension 28,37,39,49,53,57 .One longitudinal cohort enrolled participant initially free of hypertension, chronic kidney disease, and cardiovascular disease to assess racial differences in uromodulin biology 47 .Among clinical studies, uromodulin was primarily quantified in urine (19 studies), with serum or plasma used in 10 studies, and uromodulinpositive extracellular vesicles assessed in one study 38 .Measurement techniques included enzyme-linked immunosorbent assay in 14 studies, electrochemiluminescence immunoassay in 4, radioimmunoassay in 2, and western blotting in 1, while multiplex bead assays (3 studies), flow cytometry (1 study), and LC-MS/MS proteomics (1 study) were applied in selected cohorts.Genetic studies contributed > 400,00 hypertension and >150,000 normotensive participants.These analyses included 6 genome-wide association studies exclusively enrolling hypertensive individuals, 9 genome-wide association studies conducted in mixed hypertension/normotensive populations, and one genome-wide association studies focused on chronic kidney diseasehypertension 37 , using single-nucleotide polymorphism genotyping, targeted allele assays, and large-scale biobank data to investigate uromodulin genetic variation across diverse populations.Detailed information for all studies can be found in Tables 1-4 andSupplementary Tables 2-4.
Taha et al. (Wed,) reported a other. Uromodulin did not demonstrate clinically meaningful utility as a protein or genetic biomarker for hypertension across 35 studies involving over 450,000 hypertensive individuals.