Fibroblast Growth Factor 23 and Left Ventricular Hypertrophy in Chronic Kidney Disease—A Pediatric Perspective

Abstract

Cardiovascular diseases (CVD) are a hallmark in pediatric patients with chronic kidney disease (CKD) contributing to an enhanced risk of all-cause and CV morbidity and mortality in these patients. The bone-derived phosphaturic hormone fibroblast growth factor (FGF) 23 progressively rises with declining kidney function to maintain phosphate homeostasis, with up to 1,000-fold increase in patients with kidney failure requiring dialysis. FGF23 is associated with the development of left ventricular hypertrophy (LVH) and thereby accounts to be a CVD risk factor in CKD. Experimentally, FGF23 directly induces hypertrophic growth of cardiac myocytes in vitro and LVH in vivo. Further, clinical studies in adult CKD have observed cardiotoxicity associated with FGF23. Data regarding prevalence and determinants of FGF23 excess in children with CKD are limited. This review summarizes current data and discusses whether FGF23 may be a key driver of LVH in pediatric CKD.

Does cardiac impairment develop in ischemic renal surgery in rats depending on the reperfusion time?

“…Similarly, renal insufficiency can ultimately lead to uremic cardiomyopathy or myocardial fibrosis [ 40 ]. The fibroblast growth factor (FGF-23) released by CKD is reported to cause myocardial hypertrophy [ 41 ]. All this evidence and many other findings in the literature indicate that kidney disease can accelerate heart disease even before it ravages the kidneys [ 42 ].…”

ERRγ-inducible FGF23 promotes alcoholic liver injury through enhancing CYP2E1 mediated hepatic oxidative stress

“…FGF23 upregulates hepatic CYP2E1 expression potentially through FGF23-PLCγ/Calcineurin-nuclear factor of activated T cells (NFAT) signaling pathway. Previous studies have demonstrated that FGF23 regulates target gene expression by activating the PLCγ/Calcineurin pathway in hepatocytes and cardiac myocytes [ [52] , [53] , [54] , [55] ]. In this study, we employed a calcineurin inhibitor, cyclosporine A (CysA), to illustrate the involvement of the PLCγ/Calcineurin pathway in FGF23-mediated upregulation of hepatic CYP2E1 expression ( Fig.…”

Interaction of Vitamin D with Peptide Hormones with Emphasis on Parathyroid Hormone, FGF23, and the Renin-Angiotensin-Aldosterone System

“…Chronic kidney disease is characterized by low αKlotho and 1,25(OH) 2 D levels and elevated circulating FGF23. High FGF23 levels are associated with left ventricular hypertrophy and heart failure [ 138 ]. Furthermore, increased circulating FGF23 additionally exacerbates 1,25(OH) 2 D deficiency, possibly contributing to faster progression of CKD and increased mortality in these patients.…”