Phosphate control in reducing FGF23 levels in hemodialysis patients

PLoS One. 2018 Aug 7;13(8):e0201537. doi: 10.1371/journal.pone.0201537. eCollection 2018.

Abstract

Background: In hemodialysis patients, high levels of Fibroblast Growth Factor 23 (FGF23) predict mortality. Our study was designed to test whether the control of serum phosphate is associated with a reduction in serum FGF23 levels. Additionally other variables with a potential effect on FGF23 levels were evaluated.

Material and methods: The effect of sustained (40-weeks) control of serum phosphate on FGF23 levels (intact and c-terminal) was evaluated in 21 stable hemodialysis patients that were not receiving calcimimetics or active vitamin D. Patients received non-calcium phosphate binders to maintain serum phosphate below 4.5 mg/dl. In an additional analysis, values of intact-FGF23 (iFGF23) and c-terminal FGF23 (cFGF23) from 150 hemodialysis patients were correlated with parameters of mineral metabolism and inflammation. Linear mixed models and linear regression were performed to evaluate longitudinal trajectories of variables and the association between FGF23 and the other variables examined.

Results: During the 40-week treatment, 12 of 21 patients achieved the target of serum phosphate <4.5 mg/dl. In these 12 patients, iFGF23 decreased to less than half whereas cFGF23 did not reduce significantly. In patients with serum phosphate >4.5 mg, iFGF23 and cFGF23 increased two and four-fold respectively as compared with baseline. Furthermore, changes in serum phosphate correlated with changes in C-reactive protein (hs-CRP). In our 150 hemodialysis patients, those in the higher tertile of serum phosphate also showed increased hs-CRP, iPTH, iFGF23 and cFGF23. Multiple regression analysis revealed that iFGF23 levels directly correlated with both serum phosphate and calcium, whereas cFGF23 correlated with serum phosphate and hs-CRP but not with calcium.

Conclusions: The control of serum phosphate reduced iFGF23. This reduction was also associated with a decreased in inflammatory parameters. Considering the entire cohort of hemodialysis patients, iFGF23 levels correlated directly with serum phosphate levels and also correlated inversely with serum calcium concentration. The levels of cFGF23 were closely related to serum phosphate and parameters of inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • C-Reactive Protein / analysis
  • Calcium / blood
  • Chelating Agents / therapeutic use*
  • Cross-Sectional Studies
  • Female
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / blood*
  • Humans
  • Hyperphosphatemia / blood
  • Hyperphosphatemia / drug therapy*
  • Hyperphosphatemia / etiology
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Phosphates / blood*
  • Prospective Studies
  • Renal Dialysis / adverse effects*
  • Renal Insufficiency, Chronic / blood*
  • Renal Insufficiency, Chronic / mortality
  • Renal Insufficiency, Chronic / therapy
  • Survival Analysis
  • Treatment Outcome

Substances

  • Chelating Agents
  • FGF23 protein, human
  • Phosphates
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor-23
  • C-Reactive Protein
  • Calcium

Grants and funding

This study was supported by grants from the National Institute of Health Carlos III (FIS 14/00638, FIS 17/01785, and FIS 17-01010), the Consejeria de Salud of Junta de Andalucía (PI-0311-2014 and PI-0136-2016), the REDinREN from the National Institute of Health Carlos III and the EUTox Work group. JR Muñoz-Castañeda is a senior researcher supported by the Nicolás Monardes Programme from Consejeria de Salud-SAS (Junta de Andalucía). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.