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Update time:2019-03-11 20:04:22   【 Font: Large  Medium Small

    Uromodulin or Tamm-Horsfall protein (THP) is a 90-KDa protein of high glycosylation almost exclusively in the kidney by the epithelial cells lining the thick ascending limb (TAT) of the loop of Henle and early distal tubules. It is the most abundant protein in healthy human urine.
    The domain composition of uromodulin includes a leader peptide directing its entry in the secretory pathway, three epidermal growth factor (EGF)-like domains (EGF-Ⅱ and EGF-Ⅲ predicted to be calcium binding), a central domain of unknown function, a zona pellucida (ZP) domain, and a glycosylphosphatidylinositol-anchoring site.
    Uromodulin may contribute to colloid osmotic pressure, retards passage of positively charged electrolytes, prevents formation of supersaturated salts and their crystals. Uromodulin gene knockout mice exhibit progressive renal papillary calcification and formation of calcium oxalate stones.
    Uromodulin can defense against a urinary tract infection. When uromodulin production is increased , it is likely that the kidney is counteracting uncontrolled systemic inflammation through inhibiton of cytokine/chemokine signaling or via activation and polarization of macrophages. Studies in mice demonstrated that uromodulin binds to and inhibits the type 1 fimbriae of Escherichia coli.
    Uromodulin is also critical for modulating renal ion channel activity, salt/water balance, rental and intertubular communication.
    More recent findings that polymorphisms in uromodulin gene are strongly associated with chronic kidney disease, Mutations in uromodulin gene cause familial juvenile hyperuricemic nephropathy, medullary cystic kidney disease type 2 that autosomal dominant tubulointerstitial kidney disease.
    Lower levels of serum uromodulin may identify early kidney function loss even when serum creatinine values are still within a seemingly normal range. Serum uromodulin levels were lower in patients with CKD, albuminuria and hypertension. The levels of serum uromodulin in chronic kidney disease patients、glomerulitis patients and hypertensive are obviously lower than healthy persons.
    The concentration of uromodulin is associated with glomerular filtration rate (eGFR), higher levels of uromodulin with higher eGFR. To most patients of kidney function decline, uromodulin in urine reduces and levels are positively correlated to eGFR.
    Higher levels of urinary uromodulin may be associated with a lower risk of a urinary tract infection, a lower risk of mortality in older adults and lower odds of acute kidney injury in persons undergoing on-pump cardiac surgery.

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