Increased FGF23 protects against detrimental cardio-renal consequences during elevated blood phosphate in CKD

Erica L. Clinkenbeard, Megan L. Noonan, Joseph C. Thomas, Pu Ni, Julia M. Hum, Mohammad Aref, Elizabeth A. Swallow, Sharon Moe, Matthew Allen, Kenneth White

Research output: Contribution to journalArticle

Abstract

The phosphaturic hormone FGF23 is elevated in chronic kidney disease (CKD). The risk of premature death is substantially higher in the CKD patient population, with cardiovascular disease (CVD) as the leading mortality cause at all stages of CKD. Elevated FGF23 in CKD has been associated with increased odds for all-cause mortality; however, whether FGF23 is associated with positive adaptation in CKD is unknown. To test the role of FGF23 in CKD phenotypes, a late osteoblast/osteocyte conditional flox-Fgf23 mouse (Fgf23fl/fl/Dmp1-Cre+/-) was placed on an adenine-containing diet to induce CKD. Serum analysis showed casein-fed Cre+ mice had significantly higher serum phosphate and blood urea nitrogen (BUN) versus casein diet and Cre- genotype controls. Adenine significantly induced serum intact FGF23 in the Cre- mice over casein-fed mice, whereas Cre+ mice on adenine had 90% reduction in serum intact FGF23 and C-terminal FGF23 as well as bone Fgf23 mRNA. Parathyroid hormone was significantly elevated in mice fed adenine diet regardless of genotype, which significantly enhanced midshaft cortical porosity. Echocardiographs of the adenine-fed Cre+ hearts revealed profound aortic calcification and cardiac hypertrophy versus diet and genotype controls. Thus, these studies demonstrate that increased bone FGF23, although associated with poor outcomes in CKD, is necessary to protect against the cardio-renal consequences of elevated tissue phosphate.

Original languageEnglish (US)
JournalJCI insight
Volume4
Issue number4
DOIs
StatePublished - Feb 21 2019

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Chronic Renal Insufficiency
Phosphates
Adenine
Kidney
Caseins
Diet
Genotype
Serum
Bone and Bones
Osteocytes
Premature Mortality
Mortality
Porosity
Blood Urea Nitrogen
Cardiomegaly
Parathyroid Hormone
Osteoblasts
Cardiovascular Diseases
Hormones
Phenotype

Keywords

  • Chronic kidney disease
  • Endocrinology
  • Genetics

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Increased FGF23 protects against detrimental cardio-renal consequences during elevated blood phosphate in CKD. / Clinkenbeard, Erica L.; Noonan, Megan L.; Thomas, Joseph C.; Ni, Pu; Hum, Julia M.; Aref, Mohammad; Swallow, Elizabeth A.; Moe, Sharon; Allen, Matthew; White, Kenneth.

In: JCI insight, Vol. 4, No. 4, 21.02.2019.

Research output: Contribution to journalArticle

Clinkenbeard, Erica L. ; Noonan, Megan L. ; Thomas, Joseph C. ; Ni, Pu ; Hum, Julia M. ; Aref, Mohammad ; Swallow, Elizabeth A. ; Moe, Sharon ; Allen, Matthew ; White, Kenneth. / Increased FGF23 protects against detrimental cardio-renal consequences during elevated blood phosphate in CKD. In: JCI insight. 2019 ; Vol. 4, No. 4.
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