Named for two New York virologists, the Tamm-Horsfall mucoprotein (THMP or uromodulin) was first isolated in 1950 by Igor Tamm and Frank Horsfall. Synthesized by cells of the thick ascending limb of the loop of henle, is the most abundant urinary protein in healthy mammals. That being said, it is no surprise this protein is the matrix for tubular casts, and has been shown to have roles in multiple tubular disease states.
The 616 amino acid, 90 kDa protein was first identified by Tamm and Horsfall as a potent inhibitor of viral hemoagglutination in healthy individuals. It is thought to be protective against urinary tract infections by preventing the adhesion of fimbriated E coli to tubular epithelium. The protein has also been implicated in disease states:
Myeloma Kidney/Cast Nephropathy: Filtered monoclonal light chains bind to the THMP forming obstructing tubular casts
Rhabdomyolysis: Distal tubule obstruction occurs by binding of myoglobulin
to THMP, which may be enhanced by acidic urine.
Acute Tubular Necrosis: Increased sodium concentration as a result of damage to tubular epithelial cells causes polymerization of THMP and cast formation including the sloughed tubular cells, contributing to tubular obstruction.
Nephrolithiasis: Specifically Calcium Oxalate Monohydrate stones. In an alkaline environment, THMP may prevent crystal aggregation, but in acidic urine THMP viscosity and aggregation increases, decreasing the inhibitory properties thought to prevent this stone formation.
Genetic Disorders: Medullary cystic kidney Disease type 2 and Familial Juvenile Hyperuricemic Nephropathy, (both characterized by hyperuricemia, medullary cysts, interstitial nephritis and progressive renal failure) have genetic defects located close to the human THMP gene. There is speculation that it is an alteration of the structure of THMP that accounts for these disease states.
Reference is linked above. AJKD 2003:42:4:658-676.
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ReplyDeleteCommon variants in the region of the UMOD gene, which encodes uromodulin (Tamm-Horsfall protein) have been associated with chronic kidney disease (CKD) and estimated GFR (eGFR) has been reviewed recently in JASN 2010 Feb issue. They show that urinary uromodulin levels predict incident CKD, in a prospective, case-control study of ten years duration. These findings were then externally replicated. They showed that elevated uromodulin concentrations precede the onset of CKD and associate with a common polymorphism in the UMOD region.
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