Fibroblast growth factor 23 and cardiovascular disease in patients with chronic kidney disease

Abstract Chronic kidney disease (CKD) has been known to be associated with an increased risk of cardiovascular (CV) mortality and morbidity in Japan. Although traditional risk factors contribute to the development of CV disease in CKD patients, they cannot fully explain the unacceptably high incidence of CV mortality. Recently, non-traditional risk factors, including abnormal mineral metabolism, have been suggested to be involved in the increased risk of CV events. The medical treatment of CKD-mineral bone disorders (CKD-MBD) has been associated with encouraging, but inconsistent, improvement in CV disease complications and patient survival. A better understanding of the biomarkers and mechanisms involved in left ventricular hypertrophy (LVH) and vascular calcification might improve the diagnosis and treatment of the CV disease secondary to CKD-MBD, thus improving patient survival. Recent insights into fibroblast growth factor 23 (FGF23) and its co-receptor, Klotho, have led to marked advancements in the interpretation of data about CKD-MBD and CV damage

Relationship between Fibroblast Growth Factor-23 and Mineral Metabolism in Chronic Kidney Disease

Fibroblast growth factor- (FGF-)23 is a recently discovered regulator of calcium-phosphate metabolism. FGF-23 appears to decrease in synthesis and accelerated degradation of 1,25(OH)2D. Together with its cofactor Klotho, FGF-23 maintains serum phosphate levels within the normal range by increasing renal phosphate excretion. In chronic kidney disease (CKD), FGF-23 levels rise in parallel with the decline in renal function long before a significant increase in serum phosphate concentration occurs. Both Klotho and FGF-23, linked by a receptor mechanism, affect vitamin D synthesis and parathyroid hormone (PTH) secretion. Previous studies have shown a close association between reduced FGF-23 or Klotho activities and vascular calcification. The possible association of FGF-23 and left ventricular hypertrophy or vascular dysfunction has been proposed. Finally, prospective studies have shown that high serum FGF-23 concentrations predict more rapid disease progression in CKD patients who were not on dialysis and increased mortality in patients on maintenance hemodialysis. FGF-23 may therefore prove to be an important therapeutic target for the management of CKD

Possible Link between Metabolic Syndrome and Chronic Kidney Disease in the Development of Cardiovascular Disease

Metabolic syndrome (MetS) is a clinical syndrome that consists of visceral obesity, dyslipidemia, hypertension, and impaired insulin sensitivity. Although individual components of MetS have been implicated in the development of chronic kidney disease (CKD), few studies have examined the effect of combinations of the components of MetS on the development of CKD and cardiovascular disease (CVD). The prevalence of MetS is increasing worldwide in both developing and developed countries, and early detection and treatment of MetS would be a cost-effective strategy for preventing the development of CKD. Visceral obesity and insulin resistance are two important features of MetS that may be associated with renal damage. Lifestyle modifications, including caloric restriction and exercise, are necessary to treat MetS. Initial antihypertensive therapy should consist of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. An improved understanding of the mechanism responsible for the association between MetS and renal damage should be helpful in determining the treatment regimens directed at cardiovascular and renal protection