Navarro-García José Alberto, González-Lafuente Laura, Fernández-Velasco María, Ruilope Luis M, Ruiz-Hurtado Gema
Cardiorenal Translational Laboratory, Institute of Research i + 12, Hospital Universitario 12 de Octubre, Madrid, Spain.
IdiPAZ Institute for Health Research/CIBER-CV, Hospital Universitario La Paz, Madrid, Spain.
Front Physiol. 2021 Nov 15;12:775029. doi: 10.3389/fphys.2021.775029. eCollection 2021.
Cardiorenal syndrome (CRS) is a complex disorder that refers to the category of acute or chronic kidney diseases that induce cardiovascular disease, and inversely, acute or chronic heart diseases that provoke kidney dysfunction. There is a close relationship between renal and cardiovascular disease, possibly due to the presence of common risk factors for both diseases. Thus, it is well known that renal diseases are associated with increased risk of developing cardiovascular disease, suffering cardiac events and even mortality, which is aggravated in those patients with end-stage renal disease or who are undergoing dialysis. Recent works have proposed mineral bone disorders (MBD) as the possible link between kidney dysfunction and the development of cardiovascular outcomes. Traditionally, increased serum phosphate levels have been proposed as one of the main factors responsible for cardiovascular damage in kidney patients. However, recent studies have focused on other MBD components such as the elevation of fibroblast growth factor (FGF)-23, a phosphaturic bone-derived hormone, and the decreased expression of the anti-aging factor Klotho in renal patients. It has been shown that increased FGF-23 levels induce cardiac hypertrophy and dysfunction and are associated with increased cardiovascular mortality in renal patients. Decreased Klotho expression occurs as renal function declines. Despite its expression being absent in myocardial tissue, several studies have demonstrated that this antiaging factor plays a cardioprotective role, especially under elevated FGF-23 levels. The present review aims to collect the recent knowledge about the FGF-23-Klotho axis in the connection between kidney and heart, focusing on their specific role as new therapeutic targets in CRS.
心肾综合征（CRS）是一种复杂的病症，指的是引发心血管疾病的急性或慢性肾脏疾病类别，反之亦然，即引发肾功能障碍的急性或慢性心脏疾病。肾脏疾病与心血管疾病之间存在密切关系，这可能是由于这两种疾病存在共同的风险因素。因此，众所周知，肾脏疾病与心血管疾病发生风险增加、发生心脏事件甚至死亡率升高相关，在终末期肾病患者或正在接受透析的患者中这种情况会加剧。最近的研究提出矿物质骨代谢紊乱（MBD）可能是肾功能障碍与心血管疾病转归之间的联系。传统上，血清磷酸盐水平升高被认为是导致肾病患者心血管损伤的主要因素之一。然而，最近的研究集中在其他MBD组成部分，如成纤维细胞生长因子（FGF）-23（一种由骨产生的排磷激素）升高，以及肾病患者中抗衰老因子Klotho表达降低。研究表明，FGF-23水平升高会诱导心脏肥大和功能障碍，并与肾病患者心血管死亡率增加相关。随着肾功能下降，Klotho表达降低。尽管心肌组织中不存在其表达，但多项研究表明，这种抗衰老因子发挥着心脏保护作用，尤其是在FGF-23水平升高的情况下。本综述旨在收集有关肾脏与心脏联系中FGF-23-Klotho轴的最新知识，重点关注它们作为CRS新治疗靶点的具体作用。
