A controlled study of the effects of ferric carboxymaltose on bone and haematinic biomarkers in chronic kidney disease and pregnancy

Louis L. Huang, Darren Lee, Stefanie M. Troster, Annette B. Kent, Matthew A. Roberts, Iain C. Macdougall, Lawrence P. McMahon

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

Abstract

Background: Intravenous (IV) iron can modulate fibroblast growth factor 23 (FGF23) concentrations and cause transient but significant hypophosphataemia. However, it is unknown what other markers might be involved, especially in different patient groups. This study aimed to determine changes in bone and haematinic biomarkers following IV ferric carboxymaltose (FCM) and to identify risk factors for hypophosphataemia in pregnant subjects and those with chronic kidney disease (CKD). Methods: Changes in bone [serum FGF23, fractional excretion of phosphate urinary fractional excretion of phosphate (FEPi), serum phosphate and serum vitamin D derivatives] and haematinic [plasma hepcidin, serum ferritin and transferrin saturation (TSAT)] biomarkers after 1 g of IV FCM were followed in iron-deficient pregnant and CKD patients and compared with controls (estimated glomerular filtration rate > 60 mL/min/1.73 m2). Data were collected at baseline and up to 42 days after infusion. Risk factors for post-FCM hypophosphataemia were also assessed. Results: Sixty-five subjects completed the study (control, n = 20; pregnant, n = 20; CKD, n = 25). A uniform but variable increase across groups was seen in intact FGF23 (peak Day 2), whereas c-terminal FGF23 varied markedly. Trough serum phosphate timed with the peak FEPi at Day 7, recovering by Day 21 in the pregnant group and Day 42 in other groups. Independent predictors of a low phosphate nadir included baseline phosphate, FEPi and weight-adjusted FCM dose. All groups showed an early and marked increase in plasma hepcidin (peak Day 2), serum ferritin and TSAT (peak Day 7 for both). Conclusions: Changes in bone and haematinic biomarkers differ between patient groups following IV FCM. For patients with lower serum phosphate concentrations, limiting the dose and measuring levels 7 days after administration may mitigate clinically significant hypophosphataemia.

Original languageEnglish
Pages (from-to)1628-1635
Number of pages8
JournalNephrology Dialysis Transplantation
Volume33
Issue number9
DOIs
Publication statusPublished - 1 Sep 2018

Keywords

  • ferric carboxymaltose
  • FGF23
  • hepcidin
  • hypophosphataemia
  • iron deficiency

Cite this

@article{9d332f0112314a059243f839f3d75882,
title = "A controlled study of the effects of ferric carboxymaltose on bone and haematinic biomarkers in chronic kidney disease and pregnancy",
abstract = "Background: Intravenous (IV) iron can modulate fibroblast growth factor 23 (FGF23) concentrations and cause transient but significant hypophosphataemia. However, it is unknown what other markers might be involved, especially in different patient groups. This study aimed to determine changes in bone and haematinic biomarkers following IV ferric carboxymaltose (FCM) and to identify risk factors for hypophosphataemia in pregnant subjects and those with chronic kidney disease (CKD). Methods: Changes in bone [serum FGF23, fractional excretion of phosphate urinary fractional excretion of phosphate (FEPi), serum phosphate and serum vitamin D derivatives] and haematinic [plasma hepcidin, serum ferritin and transferrin saturation (TSAT)] biomarkers after 1 g of IV FCM were followed in iron-deficient pregnant and CKD patients and compared with controls (estimated glomerular filtration rate > 60 mL/min/1.73 m2). Data were collected at baseline and up to 42 days after infusion. Risk factors for post-FCM hypophosphataemia were also assessed. Results: Sixty-five subjects completed the study (control, n = 20; pregnant, n = 20; CKD, n = 25). A uniform but variable increase across groups was seen in intact FGF23 (peak Day 2), whereas c-terminal FGF23 varied markedly. Trough serum phosphate timed with the peak FEPi at Day 7, recovering by Day 21 in the pregnant group and Day 42 in other groups. Independent predictors of a low phosphate nadir included baseline phosphate, FEPi and weight-adjusted FCM dose. All groups showed an early and marked increase in plasma hepcidin (peak Day 2), serum ferritin and TSAT (peak Day 7 for both). Conclusions: Changes in bone and haematinic biomarkers differ between patient groups following IV FCM. For patients with lower serum phosphate concentrations, limiting the dose and measuring levels 7 days after administration may mitigate clinically significant hypophosphataemia.",
keywords = "ferric carboxymaltose, FGF23, hepcidin, hypophosphataemia, iron deficiency",
author = "Huang, {Louis L.} and Darren Lee and Troster, {Stefanie M.} and Kent, {Annette B.} and Roberts, {Matthew A.} and Macdougall, {Iain C.} and McMahon, {Lawrence P.}",
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A controlled study of the effects of ferric carboxymaltose on bone and haematinic biomarkers in chronic kidney disease and pregnancy. / Huang, Louis L.; Lee, Darren; Troster, Stefanie M.; Kent, Annette B.; Roberts, Matthew A.; Macdougall, Iain C.; McMahon, Lawrence P.

In: Nephrology Dialysis Transplantation, Vol. 33, No. 9, 01.09.2018, p. 1628-1635.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - A controlled study of the effects of ferric carboxymaltose on bone and haematinic biomarkers in chronic kidney disease and pregnancy

AU - Huang, Louis L.

AU - Lee, Darren

AU - Troster, Stefanie M.

AU - Kent, Annette B.

AU - Roberts, Matthew A.

AU - Macdougall, Iain C.

AU - McMahon, Lawrence P.

PY - 2018/9/1

Y1 - 2018/9/1

N2 - Background: Intravenous (IV) iron can modulate fibroblast growth factor 23 (FGF23) concentrations and cause transient but significant hypophosphataemia. However, it is unknown what other markers might be involved, especially in different patient groups. This study aimed to determine changes in bone and haematinic biomarkers following IV ferric carboxymaltose (FCM) and to identify risk factors for hypophosphataemia in pregnant subjects and those with chronic kidney disease (CKD). Methods: Changes in bone [serum FGF23, fractional excretion of phosphate urinary fractional excretion of phosphate (FEPi), serum phosphate and serum vitamin D derivatives] and haematinic [plasma hepcidin, serum ferritin and transferrin saturation (TSAT)] biomarkers after 1 g of IV FCM were followed in iron-deficient pregnant and CKD patients and compared with controls (estimated glomerular filtration rate > 60 mL/min/1.73 m2). Data were collected at baseline and up to 42 days after infusion. Risk factors for post-FCM hypophosphataemia were also assessed. Results: Sixty-five subjects completed the study (control, n = 20; pregnant, n = 20; CKD, n = 25). A uniform but variable increase across groups was seen in intact FGF23 (peak Day 2), whereas c-terminal FGF23 varied markedly. Trough serum phosphate timed with the peak FEPi at Day 7, recovering by Day 21 in the pregnant group and Day 42 in other groups. Independent predictors of a low phosphate nadir included baseline phosphate, FEPi and weight-adjusted FCM dose. All groups showed an early and marked increase in plasma hepcidin (peak Day 2), serum ferritin and TSAT (peak Day 7 for both). Conclusions: Changes in bone and haematinic biomarkers differ between patient groups following IV FCM. For patients with lower serum phosphate concentrations, limiting the dose and measuring levels 7 days after administration may mitigate clinically significant hypophosphataemia.

AB - Background: Intravenous (IV) iron can modulate fibroblast growth factor 23 (FGF23) concentrations and cause transient but significant hypophosphataemia. However, it is unknown what other markers might be involved, especially in different patient groups. This study aimed to determine changes in bone and haematinic biomarkers following IV ferric carboxymaltose (FCM) and to identify risk factors for hypophosphataemia in pregnant subjects and those with chronic kidney disease (CKD). Methods: Changes in bone [serum FGF23, fractional excretion of phosphate urinary fractional excretion of phosphate (FEPi), serum phosphate and serum vitamin D derivatives] and haematinic [plasma hepcidin, serum ferritin and transferrin saturation (TSAT)] biomarkers after 1 g of IV FCM were followed in iron-deficient pregnant and CKD patients and compared with controls (estimated glomerular filtration rate > 60 mL/min/1.73 m2). Data were collected at baseline and up to 42 days after infusion. Risk factors for post-FCM hypophosphataemia were also assessed. Results: Sixty-five subjects completed the study (control, n = 20; pregnant, n = 20; CKD, n = 25). A uniform but variable increase across groups was seen in intact FGF23 (peak Day 2), whereas c-terminal FGF23 varied markedly. Trough serum phosphate timed with the peak FEPi at Day 7, recovering by Day 21 in the pregnant group and Day 42 in other groups. Independent predictors of a low phosphate nadir included baseline phosphate, FEPi and weight-adjusted FCM dose. All groups showed an early and marked increase in plasma hepcidin (peak Day 2), serum ferritin and TSAT (peak Day 7 for both). Conclusions: Changes in bone and haematinic biomarkers differ between patient groups following IV FCM. For patients with lower serum phosphate concentrations, limiting the dose and measuring levels 7 days after administration may mitigate clinically significant hypophosphataemia.

KW - ferric carboxymaltose

KW - FGF23

KW - hepcidin

KW - hypophosphataemia

KW - iron deficiency

UR - http://www.scopus.com/inward/record.url?scp=85061480417&partnerID=8YFLogxK

U2 - 10.1093/ndt/gfx310

DO - 10.1093/ndt/gfx310

M3 - Article

VL - 33

SP - 1628

EP - 1635

JO - Nephrology Dialysis Transplantation

JF - Nephrology Dialysis Transplantation

SN - 0931-0509

IS - 9

ER -