Abstract
Uromodulin (Umod) is the most abundant urinary protein produced by the thick ascending limb (TAL) and distal convoluted tubule (DCT) of the kidney. Its physiological functions range from the protection against urinary tract infections (UTIs) and prevention of urinary stones to the modulation of ion transport along the distal nephron. Apart from the apical release into urine, Umod is delivered to the renal interstitium and serum via basolateral secretion to fulfil immunoregulatory tasks. Mutations and polymorphisms in the Umod gene have been associated with kidney and cardiovascular diseases, whereas serum and urinary Umod levels are emerging as biomarkers of renal and cardiovascular risks and conditions. Aging is associated with a gradual decline in both serum and urinary Umod levels, which may contribute to increased risk of UTI and kidney stones and decreased urinary concentration ability in older adults. The present review synthesizes the available information on endocrine regulation of Umod production and release during healthy and pathophysiological aging to specify translational perspectives of targeting the Umod biology and assist by interpretation of serum and urinary Umod levels as biomarkers of renal and cardiovascular health.