Uromodulin: from physiology to rare and complex kidney disorders
Top Cited Papers
- 7 August 2017
- journal article
- review article
- Published by Springer Science and Business Media LLC in Nature Reviews Nephrology
- Vol. 13 (9), 525-544
- https://doi.org/10.1038/nrneph.2017.101
Abstract
Uromodulin (also known as Tamm-Horsfall protein) is exclusively produced in the kidney and is the most abundant protein in normal urine. The function of uromodulin remains elusive, but the available data suggest that this protein might regulate salt transport, protect against urinary tract infection and kidney stones, and have roles in kidney injury and innate immunity. Interest in uromodulin was boosted by genetic studies that reported involvement of the UMOD gene, which encodes uromodulin, in a spectrum of rare and common kidney diseases. Rare mutations in UMOD cause autosomal dominant tubulointerstitial kidney disease (ADTKD), which leads to chronic kidney disease (CKD). 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. These findings have opened up a new field of kidney research. In this Review we summarize biochemical, physiological, genetic and pathological insights into the roles of uromodulin; the mechanisms by which UMOD mutations cause ADTKD, and the association of common UMOD variants with complex disorders.Keywords
This publication has 156 references indexed in Scilit:
- Tamm-Horsfall Protein Regulates Circulating and Renal Cytokines by Affecting Glomerular Filtration Rate and Acting as a Urinary Cytokine TrapJournal of Biological Chemistry, 2012
- The pathogenesis and diagnosis of acute kidney injury in multiple myelomaNature Reviews Nephrology, 2011
- Activation of the Bumetanide-sensitive Na+,K+,2Cl− Cotransporter (NKCC2) Is Facilitated by Tamm-Horsfall Protein in a Chloride-sensitive MannerJournal of Biological Chemistry, 2011
- Tamm-Horsfall Glycoprotein Interacts with Renal Outer Medullary Potassium Channel ROMK2 and Regulates Its FunctionOnline Journal of Public Health Informatics, 2011
- New loci associated with kidney function and chronic kidney diseaseNature Genetics, 2010
- Finding the missing heritability of complex diseasesNature, 2009
- Dominant Renin Gene Mutations Associated with Early-Onset Hyperuricemia, Anemia, and Chronic Kidney FailureAmerican Journal of Human Genetics, 2009
- Tamm-Horsfall Protein Protects Against Urinary Tract Infection by Proteus MirabilisJournal of Urology, 2009
- Multiple loci associated with indices of renal function and chronic kidney diseaseNature Genetics, 2009
- Atlas of Gene Expression in the Developing Kidney at Microanatomic ResolutionDevelopmental Cell, 2008