Relationship of Fibroblast Growth Factor 23 with Left Ventricle Mass Index and Coronary Calcificaton in Chronic Renal Disease

Abstract

Background: to evaluate the relationship between FGF23 and changes in biochemical parameters, left ventricle mass index, coronary, aortic and, valve calcifications. Methods: Totally 185 patients with chronic renal disease were included in this prospective, cross-sectional study. The patients were stratified according to GFR levels (mL/min/1.73m²) into 5 groups: ≥60, 45-59, 30-44, 15-29 and <15 (group 1-5 respectively).Biochemical parameters, serum FGF23 levels were measured. Echocardiographic assessments and Coronary artery calcification (CAC) with multidetector computerized tomography (MDCT) were done, left ventricle muscle mass (LVMI) was measured all patients. Results: Left ventricular hypertrophy (LVH), aortic and valve calcification were detected in 27.8%, 25.3% and 12% of patients respectively. CAC was detected in 18 patients. LVMI and FGF23 levels were found to increase proportionally with the severity of renal failure. A significant positive correlation between FGF-23 level and serum phosphate, log_PTH, and CaxP product was found. While a correlation between FGF-23 and valve calcification was detected, no correlation could be detected with LVMI, LVH, coronary and aortic calcification. Conclusion: In CKD, circulating FGF-23 and LVMI levels gradually increase with declining renal function such that by the time patients reach end-stage renal disease. Correlation between log_FGF23and valve calcification was significant, whereas no statistically significant relationship was found between log_FGF23and LVMI, LVH, aortic and coronary artery calcifications.

FGF23 is a novel regulator of intracellular calcium and cardiac contractility in addition to cardiac hypertrophy

“…Also, can FGF23 directly alter intracellular Ca 2ϩ ([Ca 2ϩ ] i ) and cardiac contractility? Previous studies have found a clinical association between FGF23 and LV mass (22,35,52) as well as declines in cardiac performance as measured by reduction in ejection fraction (19). However, to date no investigation has determined whether FGF23 can alter cardiac function independent of changes in cardiac hypertrophy.…”

“…Although an endocrine axis has been established between bone and kidney, a new paradigm is emerging in which FGF23 could be important in establishing an endocrine axis between bone and heart. Circulating levels of FGF23 are markedly elevated 100-to 1,000-fold in patients with chronic kidney disease (CKD) (24, 31) and are independently associated with cardiovascular morbidity and mortality (8,22,26,34,35,48,52). Specifically, an association between left ventricular (LV) hypertrophy and serum FGF23 levels has been established in CKD patients (20,36,52).…”

“…Circulating levels of FGF23 are markedly elevated 100-to 1,000-fold in patients with chronic kidney disease (CKD) (24, 31) and are independently associated with cardiovascular morbidity and mortality (8,22,26,34,35,48,52). Specifically, an association between left ventricular (LV) hypertrophy and serum FGF23 levels has been established in CKD patients (20,36,52).Nevertheless, despite strong associations between FGF23 and adverse outcomes, it remains relatively unknown whether FGF23 is simply a marker of cardiac disease risk or a direct mediator of cardiac pathology and cardiac performance. Only one study to date has analyzed the direct effects of FGF23 on the heart both in vitro and in vivo (13).…”

Gender Specific Association between Serum Fibroblast Growth Factor 23/α-Klotho and Coronary Artery and Aortic Valve Calcification

“…Several previous histological studies support the role of FGF23 in vascular calcification 15) ; serum FGF-23 concentrations were significantly associated with the degree of atheroma calcification 16) , and calcium deposition was correlated with FGF23 immunoreactivity in the coronary artery of the explanted heart 17) . Using multidetector computed tomography (MDCT), the potential association between FGF23 and CAC and/or AVC has also been clinically examined [18][19][20] , albeit with inconsistent results. However, the possibility remains that hyperphosphatemia rather than the FGF-23 level is the major factor driving vascular calcification 21) , which may also be indicated by the finding that FGF23 was not associated with arterial calcification and does not promote calcification 22) .…”

“…However, the possibility remains that hyperphosphatemia rather than the FGF-23 level is the major factor driving vascular calcification 21) , which may also be indicated by the finding that FGF23 was not associated with arterial calcification and does not promote calcification 22) . To evaluate the clinical utility of serum FGF23/ -Klotho for the detection or management of CAC/ AVC, various confounders, including calcium, phosphate, parathyroid hormone (PTH), and 1,25(OH)2D, should be considered, as observed in several recent studies 20,23) . To this end, in the current study, we investigated whether FGF23/ -Klotho levels are independently related with CAC/AVC calculated from image data obtained by 320-row MDCT.…”