Uromodulin in Kidney Health and Disease: Genetic Variants, Biomarker Applications, and Clinical Implications

Abstract

Uromodulin, also known as Tamm-Horsfall protein, is the most abundant protein in normal human urine and plays a crucial role in kidney function. This review explores the multifaceted role of uromodulin in renal physiology and pathophysiology, focusing on its genetic basis and utility as a biomarker. We systematically reviewed literature published between 2000 and 2024, analyzing studies on uromodulin's biomarker potential and genetic associations with kidney diseases. Our findings reveal that uromodulin is a promising biomarker for various renal conditions, including chronic kidney disease, acute kidney injury, and urinary tract infections. Urinary uromodulin levels correlate with kidney function and can predict disease progression and outcomes. Additionally, we examined genetic variants in the UMOD gene and their associations with kidney diseases. Several Single Nucleotide Polymorphisms (SNPs) in UMOD have been linked to an increased risk of chronic kidney disease, kidney stones, and hypertension. The interplay between genetic variants and uromodulin's biomarker capabilities offers potential for personalized medicine approaches in nephrology. However, standardization of uromodulin measurement techniques and more extensive prospective studies are needed to establish its clinical utility fully. This review synthesizes current knowledge on uromodulin's dual role as a genetically influenced protein and a renal biomarker, providing insights for future research directions and potential clinical applications in kidney disease management.