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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Abstract
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). |
| Status: | Published |
| Refereed: | Yes |
| 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: | 0194-911X |
| 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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