The relationship between circulating fibroblast growth factor 23 and bone metabolism factors in Korean hemodialysis patients.
ABSTRACT Fibroblast growth factor 23 (FGF-23) is a circulating factor that acts as a phosphaturic factor in the kidneys. It is also involved in several disorders of phosphate regulation and bone metabolism. We hypothesized that increased FGF-23 levels in patients with endstage renal disease (ESRD) on maintenance hemodialysis would be associated with increased bone demineralization, and we analyzed the relationship between FGF-23 levels and bone mineral density (BMD).
The serum level of FGF-23 was measured in this cross-sectional study, whose subjects consisted of 54 patients with ESRD on maintenance hemodialysis. Clinical parameters associated with hemodialysis and bone metabolism were measured. The relationship between serum FGF-23 and BMD and the factors affecting the serum level of FGF-23 were analyzed.
Serum FGF-23 levels were significantly higher in ESRD patients on maintenance hemodialysis than in normal persons (2961.4 vs. 30 pg/ml). Multiple regression analysis showed that increasing FGF-23 levels were associated with serum phosphate (r = 0.684, P < 0.001), but not with BMD or other bone metabolism factors. Factors affecting log(10)FGF-23 included the serum calcium phosphate product (beta = 0.603) and K (t)/V (integrated fractional clearance expressed per dialysis, beta = -0.244). These results were also seen in an analysis of the correlations based on T score or gender.
FGF-23 levels were positively associated with serum phosphate levels but were not correlated with BMD. The only factors affecting log(10)FGF-23 were the serum calcium phosphate product and K (t)/V. These findings suggest that FGF-23 may have no direct effect on bone mineralization, and further studies are warranted to examine the effects of FGF-23 on vitamin D metabolism.
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ABSTRACT: BACKGROUND: Fibroblast growth factor-23 (FGF23) is a phosphate-regulating hormone and is found to be markedly increased in patients with chronic kidney disease. The aim of the present study was to evaluate the relationship between serum FGF23 levels and mortality, including the impact of gender and cardiovascular disease (CVD), in a Japanese cohort of chronic hemodialysis (HD) patients. METHODS: Ninety-two maintenance dialysis patients (58 men; mean age 60.3 years) were included. Serum intact FGF23, calcium, phosphate, albumin, intact parathyroid hormone (PTH), and C-reactive protein were measured at baseline. CVD was defined as clinical symptoms and/or a history of CVD. RESULTS: During a median follow-up time of 53.2 months, 24 patients (26 %) died. Serum FGF23 levels were positively correlated with serum levels of calcium (r = 0.5433, P < 0.0001), phosphate (r = 0.5048, P < 0.0001), calcium × phosphate product (r = 0.6801, P < 0.0001), and intact PTH (r = 0.2710, P = 0.0090) (r = 0.27, P < 0.0001). In Cox proportional hazard models, serum FGF23 level was not associated with increased mortality risk, neither in crude nor in multivariate-adjusted models. However, in a subgroup analysis of women with previous CVD, serum FGF23 level above median was associated with higher cardiovascular event risk in crude models (hazard ratio 9.52, 95 % confidence interval 1.56-86.11, P = 0.0129). Kaplan-Meier analysis stratifying for the presence of CVD demonstrated a significant higher mortality risk in patients with history of CVD and higher serum FGF23 levels (P < 0.0001). CONCLUSION: Serum FGF23 level was not associated with increased mortality risk in this cohort of prevalent HD patients. These results suggest that the impact of FGF23 on mortality may be modified by gender and previous CVD and is blunted in the grade of hyperphosphatemia.International Urology and Nephrology 01/2013; · 1.29 Impact Factor
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ABSTRACT: This study is aimed at exploring the role of serum fibroblast growth factor-23 (FGF-23), matrix Gla (MGP) and Fetuin-A in the calcium-phosphate metabolism and estimate the value of serum FGF-23, MGP and Fetuin-A levels in predicting osteoporosis in maintenance hemodialysis (MHD) patients. This study included 64 patients who receive hemodialysis in our hospital. The serum FGF-23, MGP and Fetuin-A were analyzed by enzyme-linked immunosorbent assay (ELlSA). Bone mineral density (BMD) at the femoral neck was measured by dual-energy X-ray absorptiometry. The 64 patients (30 males, 34 females, 60.6 ± 11.3 years of age) received an average of 6.88 ± 2.94 years of dialysis. Body mass index (BMI), Kt/V, dialysis vintage, patient age, serum levels of FGF-23, Fetuin-A, bone isoenzyme of alkaline phosphatase (ALP-B), and calcium were different in statistical significance among the three groups of patients in terms of normal bone mass (N = 10), osteopenia (N = 24), or osteoporosis (N = 30). BMI, Kt/V, ALP-B, dialysis vintage and serum Fetuin-A level were identified as independent variables of femoral neck BMD by stepwise multiple regression analysis. The area under ROC curve showed that serum Fetuin-A was useful for identifying osteoporosis in MHD patients. The cutoff value corresponding to the highest Youden's index was serum Fetuin-A ≤89 μg/mL, which was defined as the optimal predictor of osteoporosis. Its sensitivity/specificity was 71%/77.8%. The incidence of osteoporosis is high in MHD patients. Serum Fetuin-A level is closely correlated with osteoporosis and it may serve as a predictor of osteoporosis.Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 09/2014; · 1.53 Impact Factor
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ABSTRACT: Fractures are common in patients with chronic kidney disease (CKD) and associated with substantially high morbidity and mortality. Bone mass measurements are commonly used to assess fracture risk in the general population, but the utility of these measurements in patients with CKD, and specifically among those on hemodialysis, is unclear. This review will outline the epidemiology and etiology of fractures in patients with CKD with a particular emphasis on men and women on hemodialysis. As well, we will summarize the published data, which describes the association between risk factors for fracture (including bone mass measurements, biochemical markers of mineral metabolism, and muscle strength) and fractures in patients with CKD. Patients with CKD suffer from fractures due to impairments in bone quantity, bone quality, and abnormalities of neuromuscular function. There is a paucity of evidence on the associations between bone quality, bone turnover markers, neuromuscular function, and fractures in patients with CKD. Furthermore, the complex etiology of fractures combined with the technical limitations of bone mineral density testing, both by dual energy X-ray absorptiometry (DXA) and by peripheral quantitative tomography (pQCT), limits the clinical utility of bone mass measurements for fracture prediction in CKD; this is particularly true among patients with stages 4 and 5 CKD. Further prospective studies to identify noninvasive measures of bone strength that can be used for fracture risk assessment are needed.Osteoporosis International 09/2011; 23(4):1191-8. · 4.04 Impact Factor