Relation between serum fibroblast growth factor-23 level and mortality in incident dialysis patients: are gender and cardiovascular disease confounding the relationship?

Olauson, Hannes; Qureshi, Abdul Rashid; Miyamoto, Tetsu; Bárány, Peter; Heimbürger, Olof; Lindholm, Bengt; Stenvinkel, Peter; Larsson, Tobias E.

doi:10.1093/ndt/gfq191

Cited by 68 publications

(44 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Since the plasma FGF-23 level is regulated by serum Pi [22,23] and vica versa [24,25], it appears that the plasma log FGF-23 levels should be different between groups. In many studies, it was reported that there was a correlation between serum FGF-23 levels and serum creatinine, phosphate, Ca x P product, and parathormon levels [7,20,26,27]. We also found a positive and signi�icant relationship between log FGF-23 levels and serum phosphate, log PTH , and Ca x P product.…”

Section: Discussionsupporting

confidence: 70%

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

Ünsal

Budak

Koç

et al. 2012

Kidney Blood Press Res

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 70%

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

Ünsal

Budak

Koç

et al. 2012

Kidney Blood Press Res

View full text Add to dashboard Cite

show abstract

“…On the other hand, in the Japanese population, Sugimoto et al [21] found no association between higher serum FGF23 levels and increased mortality risk until affected by previous CVD and also showed a gender impact on the association between serum FGF23 levels and mortality. Similarly, Olauson et al [22] reported a lack of association between serum FGF23 levels and increased mortality risk in a Swedish population, but the level of FGF23 was a risk factor for mortality in crude models among men with previous CVD [22]. In contrast, a recent study determining if peptide biomarkers can be useful to identify the risk of mortality among hemodialysis patients in a German population revealed that among the modern peptide biomarkers, only mid-regional pro-adrenomedullin and FGF23 showed an association with mortality [23].…”

Section: Discussionmentioning

confidence: 91%

Elevated Fibroblast Growth Factor 23 Concentration: Prediction of Mortality among Chronic Kidney Disease Patients

et al. 2015

View full text Add to dashboard Cite

Background: The osteocyte-derived hormone, fibroblast growth factor 23 (FGF23), regulates the phosphorus metabolism and suppresses 1,25-dihydroxyvitamin D production, thereby mitigating hyperphosphatemia in patients with renal disorders. An elevated FGF23 level is suggested to be an early biomarker of altered phosphorus metabolism in the initial stages of chronic kidney disease (CKD) and acts as a strong predictor of mortality in dialysis patients. In the Saudi population, there is no report on the FGF23 level in CKD patients to date. This study aims to estimate the plasma FGF23 levels in the Saudi population and to correlate it with its clinical manifestations in order to ascertain its role in the pathogenesis of CKD patients. Methods: The FGF23 level in the plasma samples was determined using ELISA in a diverse cohort of 89 cases with stage 3-5 CKD and 100 healthy subjects. The plasma FGF23 level was correlated with other biochemical parameters. Results: The results revealed that the FGF23 level was markedly elevated among CKD patients compared to the control group, and a significant inverse correlation was observed between the FGF23 level and glomerular filtration rate. FGF23 elevation was approximately 40-fold among stage 5 patients compared to the control, while the elevation of phosphate, parathyroid hormone (PTH) and alkaline phosphatase was 2-, 3- and 8-fold in this stage, respectively. Conclusion: Elevated FGF23 levels may have a strong correlation with the disease pathogenesis. In addition, FGF23 might be a future therapeutic target to intervene against the progression of CKD as well as to increase patient survivability.

show abstract

“…It is possible that the fall in serum 1,25-(OH) 2 D 3 to values below 20 pg/ml by the end of CKD stage 2 could be due in part to increased fi broblast growth factor-23 (FGF-23) levels, a known downregulator of CYP27B1 expression in normal kidney cells ( 103 ). Recent reports of marked increases in FGF-23 levels in CKD stage 5 dialysis patients with phosphate retention are consistent with FGF-23 playing a major role in vitamin D dysregulation and mortality in chronic kidney disease ( 104 ).…”

Section: Other Potential 25-hydroxylasesmentioning

confidence: 94%

Cytochrome P450-mediated metabolism of vitamin D

Jones

Prosser

Kaufmann

2014

Journal of Lipid Research

369

292

View full text Add to dashboard Cite

signal transduction system, the DBP-knockout mouse is normocalcemic and exhibits normal tissue distribution of vitamin D metabolites and vitamin D action despite exhibiting very low blood levels of 1,25-(OH) 2 D 3 . This unexpected phenotype raised questions about DBP's exact role: essential transporter or buffer against toxicity ( 7,8 ). Work performed on the 25-hydroxylases over the past four decades in humans and a variety of animal species has revealed that several cytochrome P450 enzymes 2 (CYP), such as CYP2R1, CYP27A1, CYP3A4, CYP2D25, and perhaps others, are capable of 25-hydroxylation of vitamin D 3 or related compounds. These CYPs can be referred to as vitamin D 3 -25-hydroxylases, and it is CYP2R1 that is emerging as the physiologically relevant enzyme ( 9 ). On the other hand, there is no ambiguity over the second step of 1 ␣ -hydroxylation or the 25-OH-D 3 -1 ␣ -hydroxylase enzyme responsible, which is carried by a single cytochrome P450 2 named CYP27B1 ( 10-12 ). The inactivation of vitamin D is carried out by the mitochondrial enzyme, 25-hydroxyvitamin D 3 -24-hydroxylase, fi rst described in the early 1970s and initially believed to be involved solely in the renal 24-hydroxylation of 25-OH-D 3 ( 13 ). Work performed over the last 35 years has shown that 24-hydroxylase enzyme activity is the result of CYP24A1 ( 5, 14 ). CYP24A1 catalyzes the conversion of both 25-OH-D 3 and 1,25-(OH) 2 D 3 into a series of 24-and 23-hydroxylated products targeted for excretion along well-established pathways culminating in the water-soluble biliary metabolite calcitroic acid or a 26,23-lactone.This article assembles the most currently pertinent literature on the activating and inactivating enzymes of vitamin D metabolism and highlights protein structure and enzymatic properties, crystal structures, gene organization, and The activation of vitamin D 3 is accomplished by sequential steps of 25-hydroxylation to produce the main circulating form, 25-hydroxyvitamin D (25-OH-D 3 ), followed by 1 ␣ -hydroxylation to the hormonal form, 1 ␣ ,25-dihydroxyvitamin D 3 (1,25-(OH) 2 D 3 ) ( 1 ) ( Fig. 1 ). The initial step of 25-hydroxylation occurs in the liver ( 2 ), and the second step occurs both in the kidney and extrarenal sites ( 3, 4 ). The fat-soluble vitamin D and its metabolites are transported from one tissue to another on the vitamin D-binding protein (DBP), which shows different affi nity for the individual metabolites ( 5 ). The cell-surface receptor megalin-cubilin is thought to facilitate the endocytosis of a DBP-bound 25-OH-D 3 into a number of cell types, especially kidney cells ( 6 ). While it is widely believed that DBP is an essential component of the vitamin D

show abstract

Relation between serum fibroblast growth factor-23 level and mortality in incident dialysis patients: are gender and cardiovascular disease confounding the relationship?

Cited by 68 publications

References 23 publications

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

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

Elevated Fibroblast Growth Factor 23 Concentration: Prediction of Mortality among Chronic Kidney Disease Patients

Cytochrome P450-mediated metabolism of vitamin D

Contact Info

Product

Resources

About