Patients with chronic kidney disease (CKD) are at increased risk of mortality, mainly from cardiovascular disease. Moreover, abnormal mineral and bone metabolism, the so-called CKD-mineral and bone disorder (MBD), occurs from early stages of CKD. This CKD-MBD presents a strong cardiovascular risk for CKD patients. Discovery of fibroblast growth factor 23 (FGF23) has altered our understanding of CKD-MBD and has revealed more complex cross-talk and endocrine feedback loops between the kidney, parathyroid gland, intestines, and bone. During the past decade, reports of clinical studies have described the association between FGF23 and cardiovascular risks, left ventricular hypertrophy, and vascular calcification. Recent translational reports have described the existence of FGF23-Klotho axis in the vasculature and the causative effect of FGF23 on cardiovascular disease. These findings suggest FGF23 as a promising target for novel therapeutic approaches to improve clinical outcomes of CKD patients. 1. Introduction Patients with chronic kidney disease (CKD), particularly end-stage renal disease (ESRD), face an increased risk of mortality, mainly from cardiovascular disease (CVD) [1–4]. Recent reports of clinical studies have described CKD as an independent risk factor for CVD from its early stages [1, 2]. Among ESRD patients, the risk of cardiovascular mortality is 10–100 times greater than in healthy individuals [3, 4]. Structural and functional alterations of the cardiovascular system, for example, endothelial dysfunction, arterial stiffening, left ventricular hypertrophy (LVH), and vascular calcification, contribute to the overt risk of CVD. Traditional cardiovascular risk factors such as hypertension, hyperlipidemia, and diabetes do not completely explain high cardiovascular risk in CKD patients. Interventions that have been successful in the general population have failed to decrease mortality in CKD patients [5]. Nontraditional factors, particularly those related to abnormal mineral metabolism, hyperparathyroidism, and vitamin D deficiency, which have been grouped together as CKD-related mineral and bone disorders (CKD-MBD), have emerged to explain the increased risk of CVD in these patients [6]. Abnormalities of mineral and bone metabolism occur early in the course of CKD and progress as the glomerular filtration rate (GFR) declines [7]. Traditionally, the pathogenesis of CKD-MBD has been ascribed to a decline in 1,25-dihydroxyvitamin D (1,25(OH)2D) levels, leading to increases in serum parathyroid hormone (PTH) and subsequent alterations in calcium and
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