The role of uromodulin in salt-sensitive hypertension

Mary, S. , Boder, P., Padmanabhan, S. , McBride, M. W. , Graham, D. , Delles, C. and Dominiczak, A. F. (2022) The role of uromodulin in salt-sensitive hypertension. Hypertension, 79, pp. 2419-2429. (doi: 10.1161/HYPERTENSIONAHA.122.19888) (PMID:36378920) (PMCID:PMC9553220)

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The exclusive expression of uromodulin in the kidneys has made it an intriguing protein in kidney and cardiovascular research. Genome-wide association studies discovered variants of uromodulin that are associated with chronic kidney diseases and hypertension. Urinary and circulating uromodulin levels reflect kidney and cardiovascular health as well as overall mortality. More recently, Mendelian randomization studies have shown that genetically driven levels of uromodulin have a causal and adverse effect on kidney function. On a mechanistic level, salt sensitivity is an important factor in the pathophysiology of hypertension, and uromodulin is involved in salt reabsorption via the NKCC2 (Na+-K+-2Cl− cotransporter) on epithelial cells of the ascending limb of loop of Henle. In this review, we provide an overview of the multifaceted physiology and pathophysiology of uromodulin including recent advances in its genetics; cellular trafficking; and mechanistic and clinical studies undertaken to understand the complex relationship between uromodulin, blood pressure, and kidney function. We focus on tubular sodium reabsorption as one of the best understood and pathophysiologically and clinically most important roles of uromodulin, which can lead to therapeutic interventions.

Item Type:Articles
Additional Information:P. Boder is supported by a British Heart Foundation PhD studentship (FS/18/58/34179). M.W. McBride is supported by FS/17/63/33485. S. Padmanabhan, C. Delles, and A.F. Dominiczak are supported by a British Heart Foundation Centre of Research Excellence Award (RE/18/6/34217). S. Padmanabhan is funded by the Medical Research Council (MR/M016560/1; AIM-HY Study), the British Heart Foundation (BHF CS/16/1/31878), and Heart Research UK (RG2690/21/24). A.F. Dominiczak and S. Padmanabhan acknowledge funding from the UKRI Strength in Places Fund (SIPF00007/1).
Glasgow Author(s) Enlighten ID:McBride, Dr Martin and Boder, Philipp and Samji, Dr Sheon and Padmanabhan, Professor Sandosh and Dominiczak, Professor Anna and Delles, Professor Christian and Graham, Dr Delyth
Authors: Mary, S., Boder, P., Padmanabhan, S., McBride, M. W., Graham, D., Delles, C., and Dominiczak, A. F.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Hypertension
Publisher:American Heart Association
ISSN (Online):1524-4563
Published Online:12 September 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in Hypertension 79:2419–2429
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
303944BHF Centre of ExcellenceColin BerryBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science
305659BHF 4-Year PhD Studentship Award 2018Rhian TouyzBritish Heart Foundation (BHF)FS/18/58/34179CAMS - Cardiovascular Science