Clinical Potential of Targeting Fibroblast Growth Factor-23 and αKlotho in the Treatment of Uremic Cardiomyopathy

Chronic kidney disease is highly prevalent, affecting 10% to 15% of the adult population worldwide and is associated with increased cardiovascular morbidity and mortality. As chronic kidney disease worsens, a unique cardiovascular phenotype develops characterized by heart muscle disease, increased arterial stiffness, atherosclerosis, and hypertension. Cardiovascular risk is multifaceted, but most cardiovascular deaths in patients with advanced chronic kidney disease are caused by heart failure and sudden cardiac death. While the exact drivers of these deaths are unknown, they are believed to be caused by uremic cardiomyopathy: a specific pattern of myocardial hypertrophy, fibrosis, with both diastolic and systolic dysfunction. Although the pathogenesis of uremic cardiomyopathy is likely to be multifactorial, accumulating evidence suggests increased production of fibroblast growth factor-23 and αKlotho deficiency as potential major drivers of cardiac remodeling in patients with uremic cardiomyopathy. In this article we review the increasing understanding of the physiology and clinical aspects of uremic cardiomyopathy and the rapidly increasing knowledge of the biology of both fibroblast growth factor-23 and αKlotho. Finally, we discuss how dissection of these pathological processes is aiding the development of therapeutic options, including small molecules and antibodies, directly aimed at improving the cardiovascular outcomes of patients with chronic kidney disease and end-stage renal disease.

Errataetall:

ErratumIn: J Am Heart Assoc. 2020 Jul 21;9(14):e014566. - PMID 32674722

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:9

Enthalten in:

Journal of the American Heart Association - 9(2020), 7 vom: 07. Apr., Seite e016041

Sprache:

Englisch

Beteiligte Personen:

Law, Jonathan P [VerfasserIn]
Price, Anna M [VerfasserIn]
Pickup, Luke [VerfasserIn]
Radhakrishnan, Ashwin [VerfasserIn]
Weston, Chris [VerfasserIn]
Jones, Alan M [VerfasserIn]
McGettrick, Helen M [VerfasserIn]
Chua, Winnie [VerfasserIn]
Steeds, Richard P [VerfasserIn]
Fabritz, Larissa [VerfasserIn]
Kirchhof, Paulus [VerfasserIn]
Pavlovic, Davor [VerfasserIn]
Townend, Jonathan N [VerfasserIn]
Ferro, Charles J [VerfasserIn]

Links:

Volltext

Themen:

αKlotho
62031-54-3
7Q7P4S7RRE
Cardiorenal syndrome
EC 3.2.1.31
FGF23
FGF23 protein, human
Fibroblast Growth Factor-23
Fibroblast Growth Factors
Fibroblast growth factor
Glucuronidase
Growth factor
Journal Article
Kidney
Klotho Proteins
Recombinant Proteins
Research Support, Non-U.S. Gov't
Review
Treatment

Anmerkungen:

Date Completed 08.03.2021

Date Revised 04.12.2021

published: Print-Electronic

ErratumIn: J Am Heart Assoc. 2020 Jul 21;9(14):e014566. - PMID 32674722

Citation Status MEDLINE

doi:

10.1161/JAHA.120.016041

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM307987825