Effect of ferric citrate hydrate on FGF23 and PTH levels in patients with non-dialysis-dependent chronic kidney disease with normophosphatemia and iron deficiency
- 202 Downloads
In patients with normophosphatemia with chronic kidney disease (CKD), fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH) increase urinary phosphate excretion while maintaining serum phosphate within the normal range. Recent reports have shown that, in this stage, phosphate binders do not decrease serum FGF23 and PTH levels. Iron deficiency promotes transcription of FGF23 and iron-supplementation for iron deficiency decreases serum FGF23 levels. We hypothesized that ferric citrate hydrate, an iron-based phosphate binder, will decrease serum FGF23 levels in patients with non-dialysis-dependent CKD with normophosphatemia and iron deficiency.
This was a single-center, randomized, open-label interventional study. The inclusion criteria were as follows: (1) eGFR < 45 mL/min/1.73 m2, (2) normophosphatemia, (3) iron deficiency. Patients were assigned to the following groups: ferric citrate hydrate (FCH)-group, sodium ferrous citrate (SFC)-group, and control-group. After 12 weeks of intervention, we evaluated serum FGF23 levels and CKD-mineral bone disorder markers.
There were 17 patients in the FCH-group, 14 in the SFC-group, and 9 in the control-group. The serum ferritin levels increased in the FCH-group and SFC-group compared with baseline. Serum FGF23 levels were unchanged; the change in the FCH-group was from 52.91 RU/mL (42.48–72.91) to 40.00 RU/mL (30.30–58.13) (P = 0.1764). However, in the FCH-group, serum PTH levels significantly decreased compared with baseline, from 68.00 pg/mL (49.00–141.00) to 60.00 pg/mL (44.00–144.00) (P = 0.0101).
Iron-based phosphate binder did not decrease serum FGF23 levels, but decreased serum PTH levels.
KeywordsFGF23 PTH Ferric citrate hydrate Iron deficiency Normophosphatemia
Compliance with ethical standards
Conflict of interest
The authors have no conflicts of interest to disclose.
Human and animal rights (with IRB approval number)
The study was conducted in accordance with the ethical guidelines of the Declaration of Helsinki and was approved by the human research committee at our institution (authorization No. E15-16).
Informed consent was obtained from all individual participants included in the study.
- 1.Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int Suppl. 2009; 113:S1–130.Google Scholar
- 2.Fukagawa M, Yokoyama K, Koiwa F, Taniguchi M, Shoji T, Kazama JJ, Komaba H, Ando R, Kakuta T, Fujii H, Nakayama M, Shibagaki Y, Fukumoto S, Fujii N, Hattori M, Ashida A, Iseki K, Shigematsu T, Tsukamoto Y, Tsubakihara Y, Tomo T, Hirakata H, Akizawa T. CKD-MBD Guideline Working Group.; Japanese Society for Dialysis Therapy. Clinical practice guideline for the management of chronic kidney disease-mineral and bone disorder. Ther Apher Dial. 2013; 17:247–88.CrossRefPubMedGoogle Scholar
- 4.Isakova T, Xie H, Yang W, Xie D, Anderson AH, Scialla J, Wahl P, Gutiérrez OM, Steigerwalt S, He J, Schwartz S, Lo J, Ojo A, Sondheimer J, Hsu CY, Lash J, Leonard M, Kusek JW, Feldman HI, Wolf M. Chronic Renal Insufficiency Cohort (CRIC) Study Group. Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. JAMA. 2011;305:2432–9.CrossRefPubMedPubMedCentralGoogle Scholar
- 5.Fliser D, Kollerits B, Neyer U, Ankerst DP, Lhotta K, Lingenhel A, Ritz E, Kronenberg F; MMKD Study Group., Kuen E, König P, Kraatz G, Mann JF, Müller GA, Köhler H, Riegler P. Fibroblast growth factor 23 (FGF23) predicts progression of chronic kidney disease: the Mild to Moderate Kidney Disease (MMKD) Study. J Am Soc Nephrol. 2007;18:2600–8.CrossRefPubMedGoogle Scholar
- 8.Ketteler M, Rix M, Fan S, Pritchard N, Oestergaard O, Chasan-Taber S, Heaton J, Duggal A, Kalra PA. Efficacy and tolerability of sevelamer carbonate in hyperphosphatemic patients who have chronic kidney disease and are not on dialysis. Clin J Am Soc Nephrol. 2008;3:1125–30.CrossRefPubMedPubMedCentralGoogle Scholar
- 10.Oliveira RB, Cancela AL, Graciolli FG, Dos Reis LM, Draibe SA, Cuppari L, Carvalho AB, Jorgetti V, Canziani ME, Moysés RM. Early control of PTH and FGF23 in normophosphatemic CKD patients: a new target in CKD-MBD therapy? Clin J Am Soc Nephrol. 2010;5:286–91.CrossRefPubMedPubMedCentralGoogle Scholar
- 15.Seifert ME1, de las Fuentes L, Rothstein M, Dietzen DJ, Bierhals AJ, Cheng SC, Ross W, Windus D, Dávila-Román VG, Hruska KA. Effects of phosphate binder therapy on vascular stiffness in early-stage chronic kidney disease. Am J Nephrol. 2013;38:158–67. doi: https://doi.org/10.1159/000353569. Epub 2013 Aug 7.CrossRefPubMedGoogle Scholar
- 16.Isakova T, Barchi-Chung A, Enfield G, Smith K, Vargas G, Houston J, Xie H, Wahl P, Schiavenato E, Dosch A, Gutiérrez OM, Diego J, Lenz O, Contreras G, Mendez A, Weiner RB, Wolf M. Effects of dietary phosphate restriction and phosphate binders on FGF23 levels in CKD. Clin J Am Soc Nephrol. 2013;8:1009–18. https://doi.org/10.2215/CJN.09250912. Epub 2013 Mar 7.CrossRefPubMedPubMedCentralGoogle Scholar
- 17.Ureña-Torres P, Prié D, Keddad K, Preston P, Wilde P, Wan H, Copley JB. Changes in fibroblast growth factor 23 levels in normophosphatemic patients with chronic kidney disease stage 3 treated with lanthanum carbonate: results of the PREFECT study, a phase 2a, double blind, randomized, placebo-controlled trial. BMC Nephrol. 2014;15:71. https://doi.org/10.1186/1471-2369-15-71.CrossRefPubMedPubMedCentralGoogle Scholar
- 24.Block GA, Fishbane S, Rodriguez M, Smits G, Shemesh S, Pergola PE, Wolf M, Chertow GM. A 12-week, double-blind, placebo-controlled trial of ferric citrate for the treatment of iron deficiency anemia and reduction of serum phosphate in patients with CKD Stages 3–5. Am J Kidney Dis. 2015;65:728–36.CrossRefPubMedGoogle Scholar