Fibroblast growth factor 23 correlates with volume status in haemodialysis patients and is not reduced by haemodialysis

Humalda, Jelmer K.; Riphagen, Ineke J.; Assa, Solmaz; Hummel, Yoran M.; Westerhuis, Ralf; Vervloet, Marc G.; Voors, Adriaan A.; Navis, Gerjan; Franssen, Casper F. M.; Borst, Martin H. de

doi:10.1093/ndt/gfv393

Cited by 18 publications

(19 citation statements)

References 43 publications

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“…The identified determinant factors of FGF23 are age, phosphate, glomerular filtration rate, inflammation [12,13], iron markers, volume status [14] and PTH [15]. We observed a positive relation between FGF23 and phosphate, consistent with the stimulating effect of phosphate on the FGF23 production with the lack of phosphaturic effect of FGF23 by the lack of renal function.…”

Section: Discussionsupporting

confidence: 73%

Effects of L-Carnitine on Mineral Metabolism in the Multicentre, Randomized, Double Blind, Placebo-Controlled CARNIDIAL Trial

et al. 2018

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Background: The use of L-carnitine has been proposed in haemodialysis (HD) when deficiency is present to improve anaemia resistant to erythropoietin stimulating agent, intradialytic hypotension or cardiac failure. We tested the effects of L-carnitine supplementation on parameters of chronic kidney disease-mineral bone disorder. Methods: CARNIDIAL was a randomized, double-blinded trial having included 92 incident HD subjects for a 1-year period to receive L-carnitine versus placebo. Determinant factors of C-terminal fibroblast growth factor 23 (cFGF23) and intact FGF23 were studied including Klotho level. The L-carnitine effect on mineral metabolism was analyzed between groups by mixed linear models for repeated measurements. Results: Klotho was below the lower limit of quantification (LLOQ) in 55% of the 163 samples. In multivariate analysis, cFGF23 was positively correlated with calcium and phosphate and was higher in subjects having Klotho > LLOQ. No correlation existed between Klotho and phosphate and phosphate was even higher in subjects having Klotho > LLOQ (p < 0.001). Both forms of FGF23 were not related to iron markers nor to IV iron dose. No L-carnitine effect was detected on parathyroid hormone (PTH) or FGF23 during the study period where PTH slightly decreased over time, whereas FGF23 increased. But calcium and phosphate increased more in the L-carnitine group. Conclusion: L-carnitine supplementation increased calcium and phosphate plasma concentrations with no detected downregulation effect on PTH and FGF23. (Clinical Trial 00322322, May 5, 2006).

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Section: Discussionsupporting

confidence: 73%

Effects of L-Carnitine on Mineral Metabolism in the Multicentre, Randomized, Double Blind, Placebo-Controlled CARNIDIAL Trial

et al. 2018

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“…FGF23 has recently been recognized as a volume overload marker in hemodialysis population (17)(18)(19)(20). However, our study did not find any significant relationship between FGF23 levels and volume overload.…”

Section: Discussioncontrasting

confidence: 92%

“…Several studies have concluded that FGF23 induces left ventricular hypertrophy (LVH) and is associated with cardiovascular disease in these patients (23)(24)(25). In addition, few studies have recently reported a definite relationship between hypervolemia and plasma FGF23 in hemodialysis patients (17,20). Recently, Unver et al (17) conducted a prospective study on 97 hemodialysis patients.…”

Section: Discussionmentioning

confidence: 99%

Does fibroblast growth factor 23 correlates with volume status in hemodialysis patients?

2019

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Introduction: Volume overload is a known risk factor for cardiovascular disease and stroke in hemodialysis patients. The use of fibroblast growth factor 23 (FGF23) as a volume overload marker has been validated in multiple studies. Objectives: This is a prospective cross-sectional study considering the association between FGF23 and bioimpedance-measured volume overload in hemodialysis patients. Patients and Methods: Bioimpedance analysis was performed on 43 hemodialysis patients at the end of hemodialysis to evaluate the remaining volume overload and serum FGF23 was measured before hemodialysis. Results: The results indicated no significant correlation between mean serum FGF23 levels and volume overload in hemodialysis patients (P=0.824). Conclusion: Although this study did not show any association between volume overload and FGF23, further studies are needed to define the role of FGF23 as a volume overload marker.

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“…In the setting of hemodialysis, on the other hand, the more extreme changes in volume status may result in a stronger correlation with FGF-23 concentrations. [14] …”

Section: Discussionmentioning

confidence: 99%

“…[13] Conversely, recent data suggest that changes in volume status may modulate FGF-23 concentrations at least in hemodialysis. [14] This suggests the presence of a feedback loop, where FGF-23 increases volume load, and an increase in volume may reduce FGF-23. Vice versa, a reduction in volume load may in turn increase FGF-23.…”

Section: Introductionmentioning

confidence: 99%

Response of fibroblast growth factor 23 to volume interventions in arterial hypertension and diabetic nephropathy

et al. 2016

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Fibroblast growth factor 23 (FGF-23) rises progressively in chronic kidney disease and is associated with adverse cardiovascular outcomes. FGF-23 putatively induces volume retention by upregulating the sodium-chloride cotransporter (NCC). We studied whether, conversely, interventions in volume status affect FGF-23 concentrations.We performed a post hoc analysis of 1) a prospective saline infusion study with 12 patients with arterial hypertension who received 2 L of isotonic saline over 4 hours, and 2) a randomized controlled trial with 45 diabetic nephropathy (DN) patients on background angiotensin-converting enzyme -inhibition (ACEi), who underwent 4 6-week treatment periods with add-on hydrochlorothiazide (HCT) or placebo, combined with regular sodium (RS) or low sodium (LS) diet in a cross-over design. Plasma C-terminal FGF-23 was measured by ELISA (Immutopics) after each treatment period in DN and before and after saline infusion in hypertensives.The patients with arterial hypertension were 45 ± 13 (mean ± SD) years old with an estimated glomerular filtration rate (eGFR) of 101 ± 18 mL/min/1.73 m2. Isotonic saline infusion did not affect FGF-23 (before infusion: 68 median [first to third quartile: 58–97] relative unit (RU)/mL, after infusion: 67 [57–77] RU/mL, P = 0.37). DN patients were 65 ± 9 years old. During ACEi + RS treatment, eGFR was 65 ± 25 mL/min/1.73 m2 and albuminuria 649 mg/d (230–2008 mg/d). FGF23 level was 94 (73–141) RU/mL during ACEi therapy. FGF-23 did not change significantly by add-on HCT (99 [74–148] RU/mL), LS diet (99 [75–135] RU/mL), or their combination (111 [81–160] RU/mL, P = 0.15).Acute and chronic changes in volume status did not materially change FGF-23 in hypertensive patients and DN, respectively. Our data do not support a direct feedback loop between volume status and FGF-23 in hypertension or DN.

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Fibroblast growth factor 23 correlates with volume status in haemodialysis patients and is not reduced by haemodialysis

Cited by 18 publications

References 43 publications

Effects of L-Carnitine on Mineral Metabolism in the Multicentre, Randomized, Double Blind, Placebo-Controlled CARNIDIAL Trial

Effects of L-Carnitine on Mineral Metabolism in the Multicentre, Randomized, Double Blind, Placebo-Controlled CARNIDIAL Trial

Does fibroblast growth factor 23 correlates with volume status in hemodialysis patients?

Response of fibroblast growth factor 23 to volume interventions in arterial hypertension and diabetic nephropathy

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