Indeed, mutations in THP cause a group of inherited kidney diseases, and altered THP expression is associated with increased risks of urinary tract infection, kidney stone, hypertension, hyperuricemia and acute and chronic kidney diseases.
Thus, biosynthesis of uromodulin in the DCT1 is critical for its function, structure and plasticity, suggesting novel links between uromodulin, blood pressure control and risk of kidney stones.
The aim of the study was assessment of four selected macromolecules level: osteopontin, calgranulin, uromodulin and bikunin in fresh morning urine sample in children with nephrolithiasis in the course of idiopathic hypercalciuria.
Despite an amplified biological effect of the homozygote mutation, the proband did not show a strikingly more severe clinical evolution nor was the near absence of urinary uromodulin associated with urinary tract infections or kidney stones.
Moreover, genome-wide association studies have identified common variants in UMOD that are strongly associated with risk of CKD and also with hypertension and kidney stones in the general population.
This review highlights new studies elucidating the clinical correlates of uromodulin, its association with kidney function decline, nephrolithiasis and urinary host defense.
UMOD has been linked to water/electrolyte balance and to kidney innate immunity and it is believed to protect against urinary tract infections and renal stones.
For example, common variants in the UMOD and PRKAG2 genes are associated with risk of chronic kidney disease; variants in CLDN14 with risk of kidney stone disease; and variants in or near SHROOM3, STC1, LASS2, GCKR, NAT8/ALMS1, TFDP2, DAB2, SLC34A1, VEGFA, FAM122A/PIP5K1B, ATXN2, DACH1, UBE2Q2/FBXO22, and SLC7A9, with differences in glomerular filtration rate.
In contrast to CKD, the UMOD variant confers protection against kidney stones when studied in 3,617 Icelandic and Dutch kidney stone cases and 43,201 controls (OR = 0.88, P = 5.7 x 10(-5)).
Uromodulin is known to affect the formation of calcium-containing kidney stones, and this localization of UMOD will help in studies of families with autosomal forms of nephrolithiasis.