Tamm-Horsfall Protein and Kidney Disease

Tamm-Horsfall protein (THP), or uromodulin, is a glycoprotein secreted by the renal epithelium, best known as the proteinacious framework of all urinary casts. It’s function in health is an enigma, but prevention of bacterial colonization of the urinary tract, inhibition of stone formation and the maintenance of water impermeability in the thick ascending limb of Henle are all possible. Mutations in the gene UMOD, which encodes uromodulin, cause familial juvenile hyperuricemic nephropathy, which Albert reviewed last month. Recently, a large GWAS from the CHARGE consortium identified SNPs within the UMOD gene as being associated with an increased risk of CKD, also reviewed by Nate.


In this months issue of JASN, Kottgen et al. provide a nice proof of principle of the GWAS approach, by demonstrating urinary uromodulin levels predict incident CKD, in a prospective, case-control study of ten years duration. These findings were then externally replicated. In addition, they identify a protective SNP which confers a reduced risk of CKD via reduced urinary urimodulin concentration. Although the biology remains to be determined, this finding further supports the role of uromodulin in the pathogenesis of common variant CKD.