High levels of serum fibroblast growth factor (FGF)-23 are associated with increased mortality in long haemodialysis patients

Gadrey, Jean; Terrat, Jean-Claude; Vanel, Thierry; Hurot, Jean-Marc; Lorriaux, Christie; Mayor, Brice; Chazot, Charles

doi:10.1093/ndt/gfp191

Cited by 327 publications

(244 citation statements)

References 23 publications

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“…FGF‐23 predicts the progression of CKD in human patients,13, 27, 28 and FGF‐23 concentrations are also well established as being independently associated with case fatality in CKD patients at the start of hemodialysis,14, 29 and in earlier stages of CKD 27, 28. At present, just as has been debated for many years concerning PTH, it is unclear whether FGF‐23 is a uremic toxin, or whether it is a surrogate marker for other causes of uremic toxicity.…”

Section: Discussionmentioning

confidence: 99%

Relationship between Plasma Fibroblast Growth Factor‐23 Concentration and Survival Time in Cats with Chronic Kidney Disease

Geddes

Elliott

Syme

2015

Veterinary Internal Medicne

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BackgroundFibroblast growth factor‐23 (FGF‐23) and parathyroid hormone (PTH) are commonly increased in cats with azotemic chronic kidney disease (CKD). Both are predictors of survival time in human patients, but these relationships have not previously been examined in the cat.ObjectivesTo investigate the relationship between plasma FGF‐23 and PTH concentrations at diagnosis of CKD in cats with survival time and with disease progression over 12 months.Animals214 azotemic, client‐owned cats (≥9 years).Methods Retrospective study: Biochemical and urinary variables at diagnosis of azotemic CKD, including plasma FGF‐23 and PTH concentrations were assessed as predictors of survival time (all‐cause mortality) using Cox regression, and as predictors of CKD progression over 12 months using logistic regression.ResultsIn the final multivariable Cox regression model, survival was negatively associated with plasma creatinine (P = .002) and FGF‐23 concentrations (P = .014), urine protein‐to‐creatinine ratio (P < .001) and age (P < .001). Survival was positively associated with PCV (P = .004). In the final multivariable logistic regression model, independent predictors of CKD progression included logFGF‐23 and age. Neither plasma phosphate nor PTH was found to be an independent predictor of survival time or of CKD progression.Conclusions and Clinical ImportancePlasma FGF‐23 concentration is a novel prognostic indicator in cats with CKD, independent of other factors including plasma creatinine and phosphate concentrations. Further work is required to assess if FGF‐23 contributes directly to CKD progression, but regardless these findings may make FGF‐23 a useful biomarker for predicting poorer outcomes in cats with CKD.

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Section: Discussionmentioning

confidence: 99%

Relationship between Plasma Fibroblast Growth Factor‐23 Concentration and Survival Time in Cats with Chronic Kidney Disease

Geddes

Elliott

Syme

2015

Veterinary Internal Medicne

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“…7 In long-term hemodialysis patients, high levels of carboxy-terminal FGF-23 were significantly associated with the 2-year mortality rate, with a significantly increased hazard ratio (HR) of 2.5. 8 Also, Gutierrez et al 9 demonstrated in a prospective cohort of 10,044 patients with chronic kidney disease that median carboxy-terminal FGF-23 levels were significantly higher compared to controls. Furthermore, multivariate analyses showed that increasing FGF-23 levels were associated with a monotonically increasing risk of death when examined on a continuous scale [odds ratio (OR) 1.8 (1.4-2.4), P < 0.01].…”

mentioning

confidence: 99%

Evaluation of a Method for Fibroblast Growth Factor-23: A Novel Biomarker of Adverse Outcomes in Patients with Renal Disease

Devaraj

Duncan-Staley

Jialal

2010

Metabolic Syndrome and Related Disorders

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Background: Fibroblast growth factor 23 (FGF-23), a phosphaturic peptide hormone secreted by the osteoblasts, is an important regulator of phosphorus and vitamin D metabolism. In chronic kidney disease, FGF-23 levels rise with declining kidney function. Increasing FGF-23 levels are associated with increasing risk of mortality in dialysis patients. Two assays for FGF-23 have been reported. One assay detects only full-length/intact FGF-23. In contrast, the carboxy-terminal assay recognizes both intact and carboxy-terminal FGF-23. Aim/Methods: The aim of this study was to evaluate both assays for FGF-23. Test samples were analyzed with both the intact and carboxy-terminal FGF-23 enzyme-linked immunosorbent assay (ELISA) kits according to manufacturers' instructions. Results: Carboxy-terminal FGF-23 showed very good precision with coefficients of variation (CV) ranging from 4% to 10.5%, whereas the CVs for intact FGF-23 were not very good (6-37.5%). The carboxy-terminal assay was linear, stable in plasma samples, and was not affected by common interferents. Also, the carboxy-terminal FGF-23 assay appeared to correlate better with worsening of kidney function as assessed by plasma creatinine and calculated estimated glomerular filtration rate (eGFR). Conclusion: Thus, the carboxy-terminal FGF-23 assay is robust and can be used in prospective trials to validate its utility as a biomarker of adverse outcomes in patients with renal disease.

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“…49 In addition to the possible relations between FGF-23, CKD progression, hyperparathyroidism, ventricular hypertrophy, and mortality, high FGF-23 levels are believed to correlate with vascular calcification. 50,51 Our group studied, for one year, 72 patients undergoing hemodialysis and found a positive correlation between FGF-23 levels and the vascular calcification score assessed by use of coronary tomography in the group of patients treated with sevelamer hydrochloride. 52 dIscussIon An important question that remains unanswered relates to the possible existence of other actions of FGF-23, whether that hormone is only an indirect marker of toxicity of other factors, like P, or whether it has a direct toxic effect on vascular endothelium and renal tissue.…”

Section: Fgf-23 and Clinical And Experimental Studiesmentioning

confidence: 90%

“…However, in the long run, excessive FGF-23 could favor negative clinical outcomes, such as the development of secondary hyperparathyroidism, rapid progression to CKD, and a higher mortality rate. [45][46][47][48][49][50] Thus, modulating serum FGF-23 levels can benefit patients, reducing adverse events, especially those related to disorders of the bone and mineral metabolism.…”

Section: Fgf-23: State Of the Artmentioning

confidence: 99%

“…52 Knowing that Ca overload influences FGF-23 levels can have implications with important clinical outcomes, such as mortality and cardiovascular disease, since several studies have shown the association between high FGF-23 levels and those clinical outcomes. [45][46][47][48][49][50] Considering all those unanswered questions, a recent review on the topic draws attention to the importance of better understanding the role played by P and FGF-23 in CKD, proposing to the nephrological community a randomized, controlled, long-term study using P binders in the early phases of CKD, and analyzing clinical outcomes, such as vascular calcification, bone health, and CKD progression. 69 conclusIons Several studies have consolidated the role of P as a potentially toxic element, associated with increased mortality rate.…”

Section: Fgf-23: State Of the Artmentioning

confidence: 99%

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FGF-23: estado da arte

Oliveira

Moysés

2010

J. Bras. Nefrol.

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Approximately 10 years ago, a member of the family of the fibroblast growth factors, the hormone FGF-23 (fibroblast growth factor 23) was discovered. Its currently known functions involve phosphorus (P) metabolism and inhibition of 1α hydroxylase, the enzyme responsible for the synthesis of calcitriol. That discovery led to a better understanding of the mechanisms of P control, an element associated with mortality, especially in chronic kidney disease. This study reviews several aspects of that hormone, such as its discovery, function, production, mechanism of action, and the most recent clinical studies about it. Afterwards, a discussion about the possible effects of those studies on clinical practice will be presented.

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High levels of serum fibroblast growth factor (FGF)-23 are associated with increased mortality in long haemodialysis patients

Cited by 327 publications

References 23 publications

Relationship between Plasma Fibroblast Growth Factor‐23 Concentration and Survival Time in Cats with Chronic Kidney Disease

Relationship between Plasma Fibroblast Growth Factor‐23 Concentration and Survival Time in Cats with Chronic Kidney Disease

Evaluation of a Method for Fibroblast Growth Factor-23: A Novel Biomarker of Adverse Outcomes in Patients with Renal Disease

FGF-23: estado da arte

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