High fibroblast growth factor 23 levels are associated with decreased ferritin levels and increased intravenous iron doses in hemodialysis patients.

Hirokazu Honda,Kanji Shishido,Daisuke Sanada,Takanori Shibata,Misa Ikeda,Go Takahashi,Keiko Takahashi,Tetsuo Michihata,Nozomu Hosaka,Abelardo I Aguilera

doi:10.1371/journal.pone.0176984

Abstract

A recent study demonstrated the association between inflammation, iron metabolism and fibroblast growth factor (FGF) 23. The present clinical study aimed to assess associations between anemia, iron metabolism and FGF23 in hemodialysis (HD) patients. This prospective observational study examined a cohort of prevalent HD patients (n = 282). Blood samples were obtained before dialysis sessions to measure baseline levels of hemoglobin (Hb), transferrin saturation (TSAT), ferritin, albumin-adjusted calcium (Ca), phosphate (P), intact (i)-PTH, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, intact (i)-FGF23, high sensitive (hs)-CRP, and interleukin-6. After the baseline measurement, study patients were followed-up for 6 months. Biochemical measurements were subsequently performed at 1 (Hb), 2 (TSAT and ferritin) or 3 (Ca, P and hs-CRP) month intervals. Doses of ESAs and intravenous iron supplementation during the study period were recorded. i-FGF23 was positively correlated with Ca, P, i-PTH and inversely correlated with TSAT and ferritin. However, levels of Hb and hs-CRP and doses of ESAs during the study period did not differ among the i-FGF23 tertiles, with levels of ferritin and TSAT in the higher i-FGF23 tertile being consistently lower than in the middle to lower i-FGF23 tertiles. Multivariate repeated measures analysis indicated that the higher i-FGF23 tertile was independently associated with repeated measurements of ferritin, but not of TSAT. Doses of intravenous iron supplementation were significantly increased in the higher i-FGF23 tertile in multivariate models. In conclusion, high i-FGF23 levels may be associated with prolongation of low levels of ferritin, resulting in increased usages of iron supplementation in HD patients.

Highlights

Fibroblast growth factor 23 (FGF23) is secreted by osteocytes and is involved in the regulation of phosphorus and vitamin D homeostasis
Blood samples were obtained before the baseline dialysis session to measure routine biochemical parameters, blood count, transferrin saturation (TSAT), ferritin, albumin-adjusted calcium (Ca), phosphate (P), intact (i)-parathyroid hormone (PTH), 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, intact fibroblast growth factor 23 (i-FGF23), high sensitive-CRP, and interleukin (IL)-6
Baseline i-FGF23 levels were positively correlated with Ca, P, i-PTH and inversely correlated with TSAT and ferritin (S2 Table)

Summary

Introduction

Fibroblast growth factor 23 (FGF23) is secreted by osteocytes and is involved in the regulation of phosphorus and vitamin D homeostasis. Excess FGF23 production in individuals with normal kidney function causes hypophosphatemia, low serum parathyroid hormone (PTH) levels, low plasma 1,25 dihydroxyvitamin D3 (1,25OHD) levels, and bone demineralization [1]. Another study using an animal model of functional iron deficiency due to chronic inflammation confirmed that inflammation and iron deficiency caused an increased FGF23 production and impaired FGF23 cleavage [11]. An inverse association between serum levels of iron and FGF23 has been demonstrated [12,13,14]. Randomized studies of ferric citrate, a form of iron that includes a phosphate binder, administration causes increased levels of hemoglobin and decreased both phosphate and FGF23 [15,16]. While several studies demonstrated that lanthanum could decrease FGF23 levels [18,19], oral iron supplementation provides the benefit of decreasing FGF23 levels

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