alexa The rediscovery of uromodulin (Tamm-Horsfall protein): from tubulointerstitial nephropathy to chronic kidney disease.
Immunology

Immunology

Journal of Clinical & Cellular Immunology

Author(s): Rampoldi L, Scolari F, Amoroso A, Ghiggeri G, Devuyst O

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Abstract Uromodulin (Tamm-Horsfall protein) is the most abundant protein excreted in the urine under physiological conditions. It is exclusively produced in the kidney and secreted into the urine via proteolytic cleavage. Its biological function is still not fully understood. Uromodulin has been linked to water/electrolyte balance and to kidney innate immunity. Also, studies in knockout mice demonstrated that it has a protective role against urinary tract infections and renal stone formation. Mutations in the gene encoding uromodulin lead to rare autosomal dominant diseases, collectively referred to as uromodulin-associated kidney diseases. They are characterized by progressive tubulointerstitial damage, impaired urinary concentrating ability, hyperuricemia, renal cysts, and progressive renal failure. Novel in vivo studies point at intracellular accumulation of mutant uromodulin as a key primary event in the disease pathogenesis. Recently, genome-wide association studies identified uromodulin as a risk factor for chronic kidney disease (CKD) and hypertension, and suggested that the level of uromodulin in the urine could represent a useful biomarker for the development of CKD. In this review, we summarize these recent investigations, ranging from invalidation studies in mouse to Mendelian disorders and genome-wide associations, which led to a rediscovery of uromodulin and boosted the scientific and clinical interest for this long discovered molecule. This article was published in Kidney Int and referenced in Journal of Clinical & Cellular Immunology

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