Role of Uromodulin in Salt-Sensitive Hypertension.
Hypertension
; 79(11): 2419-2429, 2022 11.
Article
em En
| MEDLINE
| ID: mdl-36378920
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.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Estudo de Associação Genômica Ampla
/
Hipertensão
Tipo de estudo:
Clinical_trials
/
Diagnostic_studies
Limite:
Humans
Idioma:
En
Revista:
Hypertension
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Reino Unido