Iron deficiency is a common cause of anemia in pediatric patients with hemodialysis-dependent chronic kidney disease (CKD-5HD). Ferric pyrophosphate citrate (FPC, Triferic®) donates iron directly to transferrin, bypassing the reticuloendothelial system and avoiding iron sequestration. Administration of FPC via dialysate or intravenously (IV) may provide a suitable therapeutic option to current IV iron preparations for these patients.
The pharmacokinetics and safety of FPC administered via dialysate and IV to patients aged < 6 years (n = 3), 6 to < 12 years (n = 4), and 12 to <18 years (n = 15) were investigated in a multicenter, open-label, two-period, single-dose study. FPC (0.07 mg iron/kg) was infused IV into the venous blood return line during hemodialysis session no. 1. FPC iron was added to bicarbonate concentrate to deliver 2 μM (110 μg/L) iron via dialysate during hemodialysis session no. 2.
Mean serum total iron concentrations peaked 3 to 4 h after administration via dialysate and 2 to 4 h after IV administration and returned to baseline by 10 h after the start of hemodialysis for both routes. Iron exposure was greater after administration via dialysate than after IV administration. The absolute amount of absorbed iron after administration via dialysate roughly doubled with increasing age, but the weight-normalized amount of absorbed iron was relatively constant across age groups (~ 0.06–0.10 mg/kg). FPC was well tolerated in the small number of patients studied.
FPC iron can be administered to pediatric patients with CKD-5HD via dialysate or by the IV route. Further study of FPC administered to maintain hemoglobin concentration is indicated.
KDOQI (2006) III. Clinical practice recommendations for anemia in chronic kidney disease in children. Am J Kidney Dis 47:S86–S108
van der Weerd NC, Grooteman MP, Nube MJ, ter Wee PM, Swinkels DW, Gaillard CA (2015) Hepcidin in chronic kidney disease: not an anaemia management tool, but promising as a cardiovascular biomarker. Neth J Med 73:108–118 PubMed
Bailie GR, Larkina M, Goodkin DA, Li Y, Pisoni RL, Bieber B, Mason N, Tong L, Locatelli F, Marshall MR, Inaba M, Robinson BM (2013) Variation in intravenous iron use internationally and over time: the Dialysis Outcomes and Practice Patterns Study (DOPPS). Nephrol Dial Transplant 28:2570–2579 CrossRefPubMed
Karaboyas A, Zee J, Morgenstern H, Nolen JG, Hakim R, Kalantar-Zadeh K, Zager P, Pisoni RL, Port FK, Robinson BM (2015) Understanding the recent increase in ferritin levels in United States dialysis patients: potential impact of changes in intravenous iron and erythropoiesis-stimulating agent dosing. Clin J Am Soc Nephrol 10:1814–1821 CrossRefPubMedPubMedCentral
Macdougall IC, Bircher AJ, Eckardt KU, Obrador GT, Pollock CA, Stenvinkel P, Swinkels DW, Wanner C, Weiss G, Chertow GM (2016) Iron management in chronic kidney disease: conclusions from a “Kidney Disease: Improving Global Outcomes” (KDIGO) Controversies Conference. Kidney Int 89:28–39 CrossRefPubMed
Gupta A, Mishra B, Handelman GJ, Crumbliss AL, Pratt R (2015) Structural, physical and functional characterization of ferric pyrophosphate citrate (FPC, Triferic), a novel iron compound for pharmaceutical applications. Nephrol Dial Transplant 30:iii299
Fishbane SN, Singh AK, Cournoyer SH, Jindal KK, Fanti P, Guss CD, Lin VH, Pratt RD, Gupta A (2015) Ferric pyrophosphate citrate (Triferic) administration via the dialysate maintains hemoglobin and iron balance in chronic hemodialysis patients. Nephrol Dial Transplant 30:2019–2026 CrossRefPubMedPubMedCentral
Pratt, RD and Gupta, A (2017) Pharmacokinetics of Triferic administered IV and via dialysate. NKF Spring Clinical Meetings 2017 Abstract #172; https://archive.aievolution.com/2017/nkf1701/index.cfm?do=abs.viewAbs&abs=1211
Müller-Wiefel DE, Sinn H, Gilli G, Scharer K (1977) Hemolysis and blood loss in children with chronic renal failure. Clin Nephrol 8:481–486 PubMed
Ellis D (1979) Serum ferritin compared with other indices of iron status in children and teenagers undergoing maintenance hemodialysis. Clin Chem 25:741–744 PubMed
- Pharmacokinetics of ferric pyrophosphate citrate administered via dialysate and intravenously to pediatric patients on chronic hemodialysis
Raymond D. Pratt
Joshua J. Zaritsky
Bradley A. Warady
- Springer Berlin Heidelberg
- Pediatric Nephrology
Journal of the International
Pediatric Nephrology Association
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X