Ferric citrate reduces fibroblast growth factor 23 levels and improves renal and cardiac function in a mouse model of chronic kidney disease.
Animals
Autoantigens
/ genetics
Collagen Type IV
/ genetics
Disease Models, Animal
Drug Evaluation, Preclinical
Ferric Compounds
/ pharmacology
Fibroblast Growth Factor-23
Fibroblast Growth Factors
/ blood
Heart
/ drug effects
Kidney
/ drug effects
Mice
Mice, Knockout
Renal Insufficiency, Chronic
/ blood
FGF23
anemia
cardiac disease
chronic kidney disease
phosphate
phosphate binder
Journal
Kidney international
ISSN: 1523-1755
Titre abrégé: Kidney Int
Pays: United States
ID NLM: 0323470
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
05
12
2018
revised:
02
07
2019
accepted:
18
07
2019
pubmed:
2
11
2019
medline:
5
11
2020
entrez:
1
11
2019
Statut:
ppublish
Résumé
Iron deficiency, anemia, hyperphosphatemia, and increased fibroblast growth factor 23 (FGF23) are common and interrelated complications of chronic kidney disease (CKD) that are linked to CKD progression, cardiovascular disease and death. Ferric citrate is an oral phosphate binder that decreases dietary phosphate absorption and serum FGF23 concentrations while increasing iron stores and hemoglobin in patients with CKD. Here we compared the effects of ferric citrate administration versus a mineral sufficient control diet using the Col4a3 knockout mouse model of progressive CKD and age-matched wild-type mice. Ferric citrate was given to knockout mice for four weeks beginning at six weeks of age when they had overt CKD, or for six weeks beginning at four weeks of age when they had early CKD. Ten-week-old knockout mice on the control diet showed overt iron deficiency, anemia, hyperphosphatemia, increased serum FGF23, hypertension, decreased kidney function, and left ventricular systolic dysfunction. Ferric citrate rescued iron deficiency and anemia in knockout mice regardless of the timing of treatment initiation. Circulating levels and bone expression of FGF23 were reduced in knockout mice given ferric citrate with more pronounced reductions observed when ferric citrate was initiated in early CKD. Ferric citrate decreased serum phosphate only when it was initiated in early CKD. While ferric citrate mitigated systolic dysfunction in knockout mice regardless of timing of treatment initiation, early initiation of ferric citrate also reduced renal fibrosis and proteinuria, improved kidney function, and prolonged life span. Thus, initiation of ferric citrate treatment early in the course of murine CKD lowered FGF23, slowed CKD progression, improved cardiac function and significantly improved survival.
Identifiants
pubmed: 31668632
pii: S0085-2538(19)30842-7
doi: 10.1016/j.kint.2019.07.026
pmc: PMC6875640
mid: NIHMS1542092
pii:
doi:
Substances chimiques
Autoantigens
0
Collagen Type IV
0
Ferric Compounds
0
Fgf23 protein, mouse
0
type IV collagen alpha3 chain
0
Fibroblast Growth Factors
62031-54-3
ferric citrate
63G354M39Z
Fibroblast Growth Factor-23
7Q7P4S7RRE
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1346-1358Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK076116
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK101730
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK102815
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK114158
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
Références
Am J Physiol Renal Physiol. 2018 Jan 1;314(1):F132-F139
pubmed: 28877877
Am J Kidney Dis. 2015 May;65(5):728-36
pubmed: 25468387
Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):E1146-55
pubmed: 22006328
Clin J Am Soc Nephrol. 2013 Nov;8(11):1968-78
pubmed: 23929933
Pediatr Nephrol. 2013 Apr;28(4):577-82
pubmed: 23117582
JAMA. 2011 Jun 15;305(23):2432-9
pubmed: 21673295
J Cell Biochem. 2010 Dec 1;111(5):1210-21
pubmed: 20717920
Nephrology (Carlton). 2019 Aug;24(8):819-826
pubmed: 30239062
Am J Kidney Dis. 1999 Jul;34(1):125-34
pubmed: 10401026
Sci Rep. 2017 Jun 13;7(1):3345
pubmed: 28611350
Clin J Am Soc Nephrol. 2014 Mar;9(3):543-52
pubmed: 24408120
J Am Heart Assoc. 2013 Jul 31;2(4):e000023
pubmed: 23902638
J Am Soc Nephrol. 2006 May;17(5):1305-15
pubmed: 16597685
N Engl J Med. 2008 Aug 7;359(6):584-92
pubmed: 18687639
Kidney Int. 2016 Nov;90(5):985-996
pubmed: 27457912
J Am Soc Nephrol. 2011 May;22(5):956-66
pubmed: 21436289
Am J Physiol Renal Physiol. 2016 Dec 1;311(6):F1369-F1377
pubmed: 27733366
Nephron. 2015;131(3):161-6
pubmed: 26551233
Endocrinology. 2013 Dec;154(12):4469-82
pubmed: 24140714
Bone Res. 2019 Apr 25;7:12
pubmed: 31044094
Comp Biochem Physiol A Mol Integr Physiol. 2007 Jan;146(1):26-39
pubmed: 17081788
Kidney Int. 2013 Jan;83(1):160-6
pubmed: 22951890
J Am Soc Nephrol. 2009 Nov;20(11):2348-58
pubmed: 19729436
J Clin Endocrinol Metab. 2012 Sep;97(9):3357-65
pubmed: 22689697
Nephrol Dial Transplant. 2018 Jul 23;:null
pubmed: 30053139
Kidney Int. 2016 Jan;89(1):135-46
pubmed: 26535997
Annu Rev Nutr. 2017 Aug 21;37:247-268
pubmed: 28715994
Circulation. 2009 May 19;119(19):2545-52
pubmed: 19414634
Biochem Biophys Res Commun. 2004 Feb 6;314(2):409-14
pubmed: 14733920
J Am Soc Nephrol. 2015 Oct;26(10):2328-39
pubmed: 25967123
J Am Soc Nephrol. 2015 Oct;26(10):2578-87
pubmed: 25736045
Am J Nephrol. 2018;47(6):406-414
pubmed: 29874654
J Am Soc Nephrol. 2019 Jun;30(6):1096-1108
pubmed: 31085679
Haematologica. 2017 Nov;102(11):e427-e430
pubmed: 28818868
Am J Physiol Endocrinol Metab. 2013 Apr 15;304(8):E863-73
pubmed: 23443925
Nephrol Dial Transplant. 2010 Dec;25(12):3983-9
pubmed: 20525642
Am J Kidney Dis. 2006 May;47(5 Suppl 3):S11-145
pubmed: 16678659
J Clin Invest. 2016 Mar 1;126(3):962-74
pubmed: 26878171
Clin Exp Nephrol. 2018 Aug;22(4):789-796
pubmed: 29181658
J Bone Miner Res. 2014 Feb;29(2):361-9
pubmed: 23873717
Cell Metab. 2015 Dec 1;22(6):1020-32
pubmed: 26437603
J Nephrol. 2011 Jan-Feb;24(1):41-9
pubmed: 20349421
J Am Coll Cardiol. 2000 Jun;35(7):1737-44
pubmed: 10841219
Eur J Heart Fail. 2015 Mar;17(3):329-39
pubmed: 25683972
J Clin Invest. 2011 Nov;121(11):4393-408
pubmed: 21985788
J Bone Miner Res. 2012 Jan;27(1):38-46
pubmed: 22031097
N Engl J Med. 2012 Jan 26;366(4):348-59
pubmed: 22276824
Am J Cardiol. 2018 Aug 15;122(4):683-688
pubmed: 29961562
Kidney Int. 2012 Nov;82(10):1061-70
pubmed: 22739976
J Clin Invest. 2012 Jul;122(7):2543-53
pubmed: 22728934
J Am Soc Nephrol. 2005 Feb;16(2):520-8
pubmed: 15615819
J Bone Miner Res. 2006 Aug;21(8):1187-96
pubmed: 16869716
J Clin Endocrinol Metab. 2011 Nov;96(11):3541-9
pubmed: 21880793
Nephrol Dial Transplant. 2018 Jul 1;33(7):1129-1137
pubmed: 29309658
Endocrinology. 2005 Nov;146(11):4647-56
pubmed: 16081635
Sci Rep. 2018 Sep 12;8(1):13701
pubmed: 30209259