*4.2. FGF23*/*Klotho and Cardiac Hypertrophy*

An increase in the FGF23/Klotho ratio is present since the early stages of CKD, and it is associated with CVD, especially with LVH [47] and vascular calcification [48,49]. Studies by Myles Wolf's group demonstrated that high levels of FGF23 caused LVH [50]. It is reasonable to speculate that FGF23 through a Wnt signaling activation might be a cause of LVH. In the experimental setting, and with respect to left ventricular remodeling, it is observed that Wnt signaling inhibition improves cardiac function; sFRP or Disheveled, both Wnt inhibitors, attenuate left ventricular remodeling [51].

Experimental studies have shown a cardioprotective e ffect of Klotho, although the mechanisms are unknown. Yu et al. [52] observed that Klotho reduced the Angiotensin II-induced hypertrophic growth of neonatal cardiomyocytes. In these cells, Angiotensin-II promoted Wnt/β-catenin activation while Klotho decreased it. Klotho administration also suppressed the expression of Angiotensin-II receptor type I showing that Klotho might be considered as an antihypertrophic factor useful in heart diseases.

A recent study has shown in hemodialysis patients that higher serum FGF23 and lower sKlotho and sclerostin (an endogenous Wnt inhibitor) levels were associated with chronic inflammation, malnutrition, secondary hyperparathyroidism, and may be considered as predictors of cardiovascular complications, such as LVH, acute coronary syndrome, or rhythm disturbances [53].
