Intact fibroblast growth factor 23 levels predict incident cardiovascular event before but not after the start of dialysis

Nakano, Chikako; Hamano, Takayuki; Fujii, Naohiko; Obi, Yoshitsugu; Matsui, Isao; Tomida, Kodo; Mikami, Satoshi; Inoue, Kazunori; Shimomura, Atsushi; Nagasawa, Yasuyuki; Okada, Noriyuki; Tsubakihara, Yoshiharu; Rakugi, Hiromi; Isaka, Yoshitaka

doi:10.1016/j.bone.2012.02.634

Cited by 76 publications

(54 citation statements)

References 64 publications

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“…However, prior reports of the association between FGF-23 and atherosclerotic events were also conflicting. 16,17,[33][34][35][36] Similar to the current study, elevated FGF-23 was not associated with incident atherosclerotic events in Figure 2. FGF-23 is associated with cardiovascular events across strata of cardiovascular risk factors.…”

Section: Discussionsupporting

confidence: 73%

“…35,36 Thus, the less robust association between atherosclerotic disease and FGF-23 in this study could represent residual confounding by incomplete ascertainment of the severity or duration of exposure to traditional atherosclerotic risk factors. Alternatively, the lower number of atherosclerotic events combined with our inability to ascertain out-of-hospital sudden cardiac death may have reduced the power of these analyses to detect a true association between FGF-23 and atherosclerotic events.…”

Section: Discussionmentioning

confidence: 90%

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Fibroblast Growth Factor-23 and Cardiovascular Events in CKD

Scialla

Xie

Rahman

et al. 2014

Journal of the American Society of Nephrology

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An elevated level of fibroblast growth factor-23 (FGF-23) is the earliest abnormality of mineral metabolism in CKD. High FGF-23 levels promote left ventricular hypertrophy but not coronary artery calcification. We used survival analysis to determine whether elevated FGF-23 is associated with greater risk of adjudicated congestive heart failure (CHF) and atherosclerotic events (myocardial infarction, stroke, and peripheral vascular disease) in a prospective cohort of 3860 participants with CKD stages 2-4 (baseline estimated GFR [eGFR], 44615 ml/min per 1.73 m 2 ). During a median follow-up of 3.7 years, 360 participants were hospitalized for CHF (27 events/1000 person-years) and 287 had an atherosclerotic event (22 events/1000 person-years). After adjustment for demographic characteristics, kidney function, traditional cardiovascular risk factors, and medications, higher FGF-23 was independently associated with graded risk of CHF (hazard ratio [HR] . Elevated FGF-23 was associated more strongly with CHF than with atherosclerotic events (P=0.02), and uniformly was associated with greater risk of CHF events across subgroups stratified by eGFR, proteinuria, prior heart disease, diabetes, BP control, anemia, sodium intake, income, fat-free mass, left ventricular mass index, and ejection fraction. Thus, higher FGF-23 is independently associated with greater risk of cardiovascular events, particularly CHF, in patients with CKD stages 2-4.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 90%

Fibroblast Growth Factor-23 and Cardiovascular Events in CKD

Scialla

Xie

Rahman

et al. 2014

Journal of the American Society of Nephrology

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383

263

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“…Multiple prospective studies have shown a consistent link between higher FGF23 concentrations and increased risk of both death and cardiovascular events across the entire spectrum of renal disease (4,5,(42)(43)(44)(45). Most studies show a near-linear increase in risk with increasing FGF23 concentrations, with available (but limited) data suggesting comparable results between cFGF23 and iFGF23 (42,45).…”

Section: Fgf23 and Adverse Outcomes In Ckdmentioning

confidence: 99%

“…Most studies show a near-linear increase in risk with increasing FGF23 concentrations, with available (but limited) data suggesting comparable results between cFGF23 and iFGF23 (42,45). With respect to renal outcomes, higher FGF23 concentrations have been associated with earlier initiation of chronic dialysis and significant decrements in renal function in patients with nondialysis-dependent CKD (4,5,36,46), again yielding improvements in event reclassification (19%) (47), and have variably predicted graft failure after kidney transplantation (44,45).…”

Section: Fgf23 and Adverse Outcomes In Ckdmentioning

confidence: 99%

The Use of Fibroblast Growth Factor 23 Testing in Patients with Kidney Disease

Smith

2014

Clinical Journal of the American Society of Nephrology

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The emergence of fibroblast growth factor 23 as a potentially modifiable risk factor in CKD has led to growing interest in its measurement as a tool to assess patient risk and target therapy. This review discusses the analytical and clinical challenges faced in translating fibroblast growth factor 23 testing into routine practice. As for other bone mineral markers, agreement between commercial fibroblast growth factor 23 assays is poor, mainly because of differences in calibration, but also, these differences reflect the variable detection of hormone fragments. Direct comparison of readout from different assays is consequently limited and likely hampers setting uniform fibroblast growth factor 23-directed targets. Efforts are needed to standardize assay output to enhance clinical use. Fibroblast growth factor 23 is robustly associated with cardiovascular and renal outcomes in patients with CKD and adds value to risk assessments based on conventional risk factors. Compared with most other mineral markers, fibroblast growth factor 23 shows better intraindividual temporal stability, with minimal diurnal and week-to-week variability, but substantial interindividual variation, maximizing discriminative power for risk stratification. Conventional therapeutic interventions for the CKD-mineral bone disorder, such as dietary phosphate restriction and use of oral phosphate binders or calcimimetics, are associated with variable efficacy at modulating circulating fibroblast growth factor 23 concentrations, like they are for other mineral metabolites. Dual therapy with dietary phosphate restriction and noncalcium-based binder use achieves the most consistent fibroblast growth factor 23-lowering effect and seems best monitored using an intact assay. Additional studies are needed to evaluate whether strategies aimed at reducing levels or antagonizing its action have beneficial effects on clinical outcomes in CKD patients. Moreover, a better understanding of the mechanisms driving fibroblast growth factor 23 elevations in CKD is needed to inform the use of therapeutic interventions targeting fibroblast growth factor 23 excess. This evidence must be forthcoming to support the use of fibroblast growth factor 23 measurement and fibroblast growth factor 23-directed therapy in the clinic.

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“…Recent clinical studies have revealed that persistent proteinuria and serum FGF-23 levels are powerful risk factors for the progression of end-stage renal disease (1)(2)(3)(4).…”

Section: Introductionmentioning

confidence: 99%

Rosiglitazone alleviates injury in rats with adenine-induced chronic kidney disease

Huang

Yan

Zheng

et al. 2013

Molecular Medicine Reports

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Abstract. Rosiglitazone (ROG) has been shown to exert beneficial effects on glycemic control and renal protection. Circulatory fibroblast growth factor-23 (FGF-23) is a novel independent risk factor for chronic kidney disease (CKD) progression. The current study focused on how ROG impacts on injury of the kidney, and whether FGF-23 is involved in the process. A total of 24 male Sprague Dawley rats, weighing 250-280 g, were divided into four groups (n=6 per group): i) Normal; ii) ROG controls, treated with ROG (10 mg/kg/day); iii) CKD models, treated with adenine (200 mg/kg/day); and iv) ROG treatment, treated with ROG (10 mg/kg/day) and adenine (200 mg/kg/day). The rats were sacrificed after four weeks, and serum, urine and kidney tissues were collected. The data revealed that the serum levels of inorganic phosphate (Pi), intact parathyroid hormone (iPTH) and FGF-23 were significantly higher in the CKD models compared with those in the normal group (P<0.01), while ROG significantly reduced the serum levels of Pi, iPTH and FGF-23 (P<0.01). The ratio of protein/creatine (Cr) in the urine and the serum levels of Cr, blood urea nitrogen and uric acid were significantly increased in the CKD models compared with the normal group (P<0.01), however, ROG significantly reduced these parameters (P<0.05). Furthermore, ROG significantly alleviated the tubule interstitial damage index of the CKD models in comparison with that of the controls. These results indicated that ROG mitigates the lesions of chronic kidney disease induced by adenine, and that the system of Pi-PTH-FGF-23 may contribute to this process. The possible mechanisms underlying this process require confirmation in future studies.

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Intact fibroblast growth factor 23 levels predict incident cardiovascular event before but not after the start of dialysis

Cited by 76 publications

References 64 publications

Fibroblast Growth Factor-23 and Cardiovascular Events in CKD

Fibroblast Growth Factor-23 and Cardiovascular Events in CKD

The Use of Fibroblast Growth Factor 23 Testing in Patients with Kidney Disease

Rosiglitazone alleviates injury in rats with adenine-induced chronic kidney disease

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