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FGF23 and klotho at the intersection of kidney and cardiovascular disease.
Edmonston, Daniel; Grabner, Alexander; Wolf, Myles.
Affiliation
  • Edmonston D; Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
  • Grabner A; Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA.
  • Wolf M; Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
Nat Rev Cardiol ; 21(1): 11-24, 2024 01.
Article de En | MEDLINE | ID: mdl-37443358
ABSTRACT
Cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD). As CKD progresses, CKD-specific risk factors, such as disordered mineral homeostasis, amplify traditional cardiovascular risk factors. Fibroblast growth factor 23 (FGF23) regulates mineral homeostasis by activating complexes of FGF receptors and transmembrane klotho co-receptors. A soluble form of klotho also acts as a 'portable' FGF23 co-receptor in tissues that do not express klotho. In progressive CKD, rising circulating FGF23 levels in combination with decreasing kidney expression of klotho results in klotho-independent effects of FGF23 on the heart that promote left ventricular hypertrophy, heart failure, atrial fibrillation and death. Emerging data suggest that soluble klotho might mitigate some of these effects via several candidate mechanisms. More research is needed to investigate FGF23 excess and klotho deficiency in specific cardiovascular complications of CKD, but the pathophysiological primacy of FGF23 excess versus klotho deficiency might never be precisely resolved, given the entangled feedback loops that they share. Therefore, randomized trials should prioritize clinical practicality over scientific certainty by targeting disordered mineral homeostasis holistically in an effort to improve cardiovascular outcomes in patients with CKD.
Sujet(s)

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Maladies cardiovasculaires / Insuffisance rénale chronique Type d'étude: Clinical_trials / Risk_factors_studies Limites: Humans Langue: En Journal: Nat Rev Cardiol Sujet du journal: CARDIOLOGIA Année: 2024 Type de document: Article Pays d'affiliation: États-Unis d'Amérique Pays de publication: Royaume-Uni

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Maladies cardiovasculaires / Insuffisance rénale chronique Type d'étude: Clinical_trials / Risk_factors_studies Limites: Humans Langue: En Journal: Nat Rev Cardiol Sujet du journal: CARDIOLOGIA Année: 2024 Type de document: Article Pays d'affiliation: États-Unis d'Amérique Pays de publication: Royaume-Uni