A review of ferric citrate clinical studies, and the rationale and design of the Ferric Citrate and Chronic Kidney Disease in Children (FIT4KiD) trial

Mark R. Hanudel; Marciana L. Laster; Anthony A. Portale; Aditi Dokras; Raymond P. Quigley; German A.Lozano Guzman; Joshua J. Zaritsky; Nicole A. Hayde; Frederick J. Kaskel; Mark M. Mitsnefes; Jorge A. Ramirez; Peace D. Imani; Poyyapakkam R. Srivaths; Amy J. Kogon; Michelle R. Denburg; Tom D. Blydt-Hansen; Loretta Z. Reyes; Larry A. Greenbaum; Darcy K. Weidemann; Bradley A. Warady; David A. Elashoff; Susan R. Mendley; Tamara Isakova; Isidro B. Salusky

doi:10.1007/s00467-022-05492-7

A review of ferric citrate clinical studies, and the rationale and design of the Ferric Citrate and Chronic Kidney Disease in Children (FIT4KiD) trial

Mark R. Hanudel, Marciana L. Laster, Anthony A. Portale, Aditi Dokras, Raymond P. Quigley, German A.Lozano Guzman, Joshua J. Zaritsky, Nicole A. Hayde, Frederick J. Kaskel, Mark M. Mitsnefes, Jorge A. Ramirez, Peace D. Imani, Poyyapakkam R. Srivaths, Amy J. Kogon, Michelle R. Denburg, Tom D. Blydt-Hansen, Loretta Z. Reyes, Larry A. Greenbaum, Darcy K. Weidemann, Bradley A. WaradyDavid A. Elashoff, Susan R. Mendley, Tamara Isakova, Isidro B. Salusky

Research output: Contribution to journal › Review article › peer-review

1 Scopus citations

Abstract

Pediatric chronic kidney disease (CKD) is characterized by many co-morbidities, including impaired growth and development, CKD-mineral and bone disorder, anemia, dysregulated iron metabolism, and cardiovascular disease. In pediatric CKD cohorts, higher circulating concentrations of fibroblast growth factor 23 (FGF23) are associated with some of these adverse clinical outcomes, including CKD progression and left ventricular hypertrophy. It is hypothesized that lowering FGF23 levels will reduce the risk of these events and improve clinical outcomes. Reducing FGF23 levels in CKD may be accomplished by targeting two key stimuli of FGF23 production—dietary phosphate absorption and iron deficiency. Ferric citrate is approved for use as an enteral phosphate binder and iron replacement product in adults with CKD. Clinical trials in adult CKD cohorts have also demonstrated that ferric citrate decreases circulating FGF23 concentrations. This review outlines the possible deleterious effects of excess FGF23 in CKD, summarizes data from the adult CKD clinical trials of ferric citrate, and presents the Ferric Citrate and Chronic Kidney Disease in Children (FIT4KiD) study, a randomized, placebo-controlled trial to evaluate the effects of ferric citrate on FGF23 in pediatric patients with CKD stages 3–4 (ClinicalTrials.gov Identifier NCT04741646).

Original language	English (US)
Pages (from-to)	2547-2557
Number of pages	11
Journal	Pediatric Nephrology
Volume	37
Issue number	11
DOIs	https://doi.org/10.1007/s00467-022-05492-7
State	Published - Nov 2022

Keywords

Chronic kidney disease
Ferric citrate
Fibroblast growth factor 23
Pediatrics

ASJC Scopus subject areas

Pediatrics, Perinatology, and Child Health
Nephrology

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10.1007/s00467-022-05492-7

Cite this

Hanudel, M. R., Laster, M. L., Portale, A. A., Dokras, A., Quigley, R. P., Guzman, G. A. L., Zaritsky, J. J., Hayde, N. A., Kaskel, F. J., Mitsnefes, M. M., Ramirez, J. A., Imani, P. D., Srivaths, P. R., Kogon, A. J., Denburg, M. R., Blydt-Hansen, T. D., Reyes, L. Z., Greenbaum, L. A., Weidemann, D. K., ... Salusky, I. B. (2022). A review of ferric citrate clinical studies, and the rationale and design of the Ferric Citrate and Chronic Kidney Disease in Children (FIT4KiD) trial. Pediatric Nephrology, 37(11), 2547-2557. https://doi.org/10.1007/s00467-022-05492-7

Hanudel, MR, Laster, ML, Portale, AA, Dokras, A, Quigley, RP, Guzman, GAL, Zaritsky, JJ, Hayde, NA, Kaskel, FJ, Mitsnefes, MM, Ramirez, JA, Imani, PD, Srivaths, PR, Kogon, AJ, Denburg, MR, Blydt-Hansen, TD, Reyes, LZ, Greenbaum, LA, Weidemann, DK, Warady, BA, Elashoff, DA, Mendley, SR, Isakova, T & Salusky, IB 2022, 'A review of ferric citrate clinical studies, and the rationale and design of the Ferric Citrate and Chronic Kidney Disease in Children (FIT4KiD) trial', Pediatric Nephrology, vol. 37, no. 11, pp. 2547-2557. https://doi.org/10.1007/s00467-022-05492-7

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title = "A review of ferric citrate clinical studies, and the rationale and design of the Ferric Citrate and Chronic Kidney Disease in Children (FIT4KiD) trial",

abstract = "Pediatric chronic kidney disease (CKD) is characterized by many co-morbidities, including impaired growth and development, CKD-mineral and bone disorder, anemia, dysregulated iron metabolism, and cardiovascular disease. In pediatric CKD cohorts, higher circulating concentrations of fibroblast growth factor 23 (FGF23) are associated with some of these adverse clinical outcomes, including CKD progression and left ventricular hypertrophy. It is hypothesized that lowering FGF23 levels will reduce the risk of these events and improve clinical outcomes. Reducing FGF23 levels in CKD may be accomplished by targeting two key stimuli of FGF23 production—dietary phosphate absorption and iron deficiency. Ferric citrate is approved for use as an enteral phosphate binder and iron replacement product in adults with CKD. Clinical trials in adult CKD cohorts have also demonstrated that ferric citrate decreases circulating FGF23 concentrations. This review outlines the possible deleterious effects of excess FGF23 in CKD, summarizes data from the adult CKD clinical trials of ferric citrate, and presents the Ferric Citrate and Chronic Kidney Disease in Children (FIT4KiD) study, a randomized, placebo-controlled trial to evaluate the effects of ferric citrate on FGF23 in pediatric patients with CKD stages 3–4 (ClinicalTrials.gov Identifier NCT04741646).",

keywords = "Chronic kidney disease, Ferric citrate, Fibroblast growth factor 23, Pediatrics",

author = "Hanudel, {Mark R.} and Laster, {Marciana L.} and Portale, {Anthony A.} and Aditi Dokras and Quigley, {Raymond P.} and Guzman, {German A.Lozano} and Zaritsky, {Joshua J.} and Hayde, {Nicole A.} and Kaskel, {Frederick J.} and Mitsnefes, {Mark M.} and Ramirez, {Jorge A.} and Imani, {Peace D.} and Srivaths, {Poyyapakkam R.} and Kogon, {Amy J.} and Denburg, {Michelle R.} and Blydt-Hansen, {Tom D.} and Reyes, {Loretta Z.} and Greenbaum, {Larry A.} and Weidemann, {Darcy K.} and Warady, {Bradley A.} and Elashoff, {David A.} and Mendley, {Susan R.} and Tamara Isakova and Salusky, {Isidro B.}",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = nov,

doi = "10.1007/s00467-022-05492-7",

language = "English (US)",

volume = "37",

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T1 - A review of ferric citrate clinical studies, and the rationale and design of the Ferric Citrate and Chronic Kidney Disease in Children (FIT4KiD) trial

AU - Hanudel, Mark R.

AU - Laster, Marciana L.

AU - Portale, Anthony A.

AU - Dokras, Aditi

AU - Quigley, Raymond P.

AU - Guzman, German A.Lozano

AU - Zaritsky, Joshua J.

AU - Hayde, Nicole A.

AU - Kaskel, Frederick J.

AU - Mitsnefes, Mark M.

AU - Ramirez, Jorge A.

AU - Imani, Peace D.

AU - Srivaths, Poyyapakkam R.

AU - Kogon, Amy J.

AU - Denburg, Michelle R.

AU - Blydt-Hansen, Tom D.

AU - Reyes, Loretta Z.

AU - Greenbaum, Larry A.

AU - Weidemann, Darcy K.

AU - Warady, Bradley A.

AU - Elashoff, David A.

AU - Mendley, Susan R.

AU - Isakova, Tamara

AU - Salusky, Isidro B.

PY - 2022/11

Y1 - 2022/11

N2 - Pediatric chronic kidney disease (CKD) is characterized by many co-morbidities, including impaired growth and development, CKD-mineral and bone disorder, anemia, dysregulated iron metabolism, and cardiovascular disease. In pediatric CKD cohorts, higher circulating concentrations of fibroblast growth factor 23 (FGF23) are associated with some of these adverse clinical outcomes, including CKD progression and left ventricular hypertrophy. It is hypothesized that lowering FGF23 levels will reduce the risk of these events and improve clinical outcomes. Reducing FGF23 levels in CKD may be accomplished by targeting two key stimuli of FGF23 production—dietary phosphate absorption and iron deficiency. Ferric citrate is approved for use as an enteral phosphate binder and iron replacement product in adults with CKD. Clinical trials in adult CKD cohorts have also demonstrated that ferric citrate decreases circulating FGF23 concentrations. This review outlines the possible deleterious effects of excess FGF23 in CKD, summarizes data from the adult CKD clinical trials of ferric citrate, and presents the Ferric Citrate and Chronic Kidney Disease in Children (FIT4KiD) study, a randomized, placebo-controlled trial to evaluate the effects of ferric citrate on FGF23 in pediatric patients with CKD stages 3–4 (ClinicalTrials.gov Identifier NCT04741646).

AB - Pediatric chronic kidney disease (CKD) is characterized by many co-morbidities, including impaired growth and development, CKD-mineral and bone disorder, anemia, dysregulated iron metabolism, and cardiovascular disease. In pediatric CKD cohorts, higher circulating concentrations of fibroblast growth factor 23 (FGF23) are associated with some of these adverse clinical outcomes, including CKD progression and left ventricular hypertrophy. It is hypothesized that lowering FGF23 levels will reduce the risk of these events and improve clinical outcomes. Reducing FGF23 levels in CKD may be accomplished by targeting two key stimuli of FGF23 production—dietary phosphate absorption and iron deficiency. Ferric citrate is approved for use as an enteral phosphate binder and iron replacement product in adults with CKD. Clinical trials in adult CKD cohorts have also demonstrated that ferric citrate decreases circulating FGF23 concentrations. This review outlines the possible deleterious effects of excess FGF23 in CKD, summarizes data from the adult CKD clinical trials of ferric citrate, and presents the Ferric Citrate and Chronic Kidney Disease in Children (FIT4KiD) study, a randomized, placebo-controlled trial to evaluate the effects of ferric citrate on FGF23 in pediatric patients with CKD stages 3–4 (ClinicalTrials.gov Identifier NCT04741646).

KW - Chronic kidney disease

KW - Ferric citrate

KW - Fibroblast growth factor 23

KW - Pediatrics

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SN - 0931-041X

VL - 37

SP - 2547

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JO - Pediatric Nephrology

JF - Pediatric Nephrology

IS - 11

ER -

A review of ferric citrate clinical studies, and the rationale and design of the Ferric Citrate and Chronic Kidney Disease in Children (FIT4KiD) trial

Abstract

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