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Ferric citrate reduces fibroblast growth factor 23 levels and improves renal and cardiac function in a mouse model of chronic kidney disease.

ABSTRACT: 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.

SUBMITTER: Francis C

PROVIDER: S-EPMC6875640 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Ferric citrate reduces fibroblast growth factor 23 levels and improves renal and cardiac function in a mouse model of chronic kidney disease.

Francis Connor C Courbon Guillaume G Gerber Claire C Neuburg Samantha S Wang Xueyan X Dussold Corey C Capella Maralee M Qi Lixin L Isakova Tamara T Mehta Rupal R Martin Aline A Wolf Myles M David Valentin V

Kidney international 20190830 6

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 ...[more]

PMID: 31668632

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Project description:Protein from plant, as opposed to animal, sources may be preferred in chronic kidney disease (CKD) because of the lower bioavailability of phosphate and lower nonvolatile acid load.Observational cross-sectional study.A total of 2,938 participants with CKD and information on their dietary intake at the baseline visit in the Chronic Renal Insufficiency Cohort Study.Percentage of total protein intake from plant sources (percent plant protein) was determined by scoring individual food items using the National Cancer Institute Diet History Questionnaire (DHQ).Metabolic parameters, including serum phosphate, bicarbonate (HCO?), potassium, and albumin, plasma fibroblast growth factor 23 (FGF-23), and parathyroid hormone (PTH), and hemoglobin levels.We modeled the association between percent plant protein and metabolic parameters using linear regression. Models were adjusted for age, sex, race, diabetes status, body mass index, estimated glomerular filtration rate, income, smoking status, total energy intake, total protein intake, 24-hour urinary sodium concentration, use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and use of diuretics.Higher percent plant protein was associated with lower FGF-23 (P = .05) and higher HCO? (P = .01) levels, but not with serum phosphate or parathyroid hormone concentrations (P = .9 and P = .5, respectively). Higher percent plant protein was not associated with higher serum potassium (P = .2), lower serum albumin (P = .2), or lower hemoglobin (P = .3) levels. The associations of percent plant protein with FGF-23 and HCO? levels did not differ by diabetes status, sex, race, CKD stage (2/3 vs. 4/5), or total protein intake (?0.8 g/kg/day vs. >0.8 g/kg/day; P-interaction >.10 for each).This is a cross-sectional study; determination of percent plant protein using the Diet History Questionnaire has not been validated.Consumption of a higher percentage of protein from plant sources may lower FGF-23 and raise HCO? levels in patients with CKD.

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Ferric citrate reduces fibroblast growth factor 23 levels and improves renal and cardiac function in a mouse model of chronic kidney disease.

Publications

Ferric citrate reduces fibroblast growth factor 23 levels and improves renal and cardiac function in a mouse model of chronic kidney disease.

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