Is Fibroblast Growth Factor 23 the New Biomarker for Cardiovascular Mortality in Chronic Kidney Disease Patients?

phosphate co-transporters in the kidney’s proximal tubules [5] . It also directly suppresses renal 1α-hydroxylase, decreasing the rate at which 25-hydroxyvitamin D is converted to its active metabolite, 1,25(OH) 2 D 3 [5] . The serum concentration of FGF23 is also highly correlated with a patient’s cystatin C eGFR [4] . Lastly, FGF23 may cause left ventricular hypertrophy by inducing cardiac myocyte hypertrophy through Klotho-independent pathways that are mediated by FGFR-dependent signaling in the calcineurin-nuclear factor of activated T cells (NFAT) cascade [6] . This effect may be reversible with FGF23 receptor blockers. A comprehensive meta-analysis confirming the value of using FGF23 as a biomarker for CVD-associated mortality has been elusive. With that in mind, we were delighted to encounter such a meta-analysis by Xue et al. [7] in this edition of the American Journal of Nephrology . Their rigorous analysis systematically evaluated 15 prospective cohort studies comprising a large sample size of 15,355 subjects with pre-dialysis CKD stages I–V. Their publication not only summarized the clear association between FGF23 and mortality, but also demonstrated the non-linear dose-dependent relationship between FGF23 and all-cause mortality [7] . In their systematic meta-analysis, a high FGF23 level was associated with an increased risk of all-cause Individuals with chronic kidney disease (CKD) are at a high risk for cardiovascular vascular disease (CVD) mortality, and advances in this field form the final frontier of CKD research [1, 2] . There has been little progress to further our understanding of this comorbidity and to improve the outcomes of CVD-associated morbidity [3] . Patients with CKD also suffer from CVD as a result of several factors such as hypertension, volume overload, diabetes mellitus, tobacco use, physical inactivity, psychosocial stress, type of CKD, proteinuria, dysregulated renin–angiotensin–aldosterone system, dyslipidemia, malnutrition, infections, thrombogenic factors, elevated homocysteine, anemia, and CKD-inherent factors. The most prominent CKD-inherent factors appear to be uremia, renal osteodystrophy, vitamin D pathophysiology, and the direct effects of fibroblast growth factor 23 (FGF23), a small molecular weight protein, on the myocardium and the large vessels [3] . FGF23 accumulates in CKD and is a potent negative regulator of circulating phosphate and 1,25(OH) 2 D 3 concentrations [4] . It also functions as an endocrine hormone by targeting cells in the kidneys and parathyroid glands, where it binds to the Klotho coreceptor and converts FGF receptor (FGFR) 1c into a specific FGF23 receptor. FGF23 induces phosphaturia and lowers serum phosphorus by reducing the number of sodium– Published online: December 23, 2016 Nephrology American Journal of