Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease.

Abstract

Hyperphosphatemia, calcitriol deficiency, and secondary hyperparathyroidism (SHPT) are common complications of chronic kidney disease (CKD). Fibroblast growth factor-23 (FGF-23) is a novel phosphaturic hormone that also inhibits renal 1alpha-hydroxylase activity and thus may be involved in the pathogenesis of SHPT. Several hypotheses were tested: that FGF-23 increases as renal function declines; is linearly associated with serum phosphate levels; is associated with increased phosphaturia independent of parathyroid hormone (PTH); and is associated with decreased calcitriol levels independent of renal function, hyperphosphatemia, and vitamin D stores. FGF-23, PTH, 25(OH)D3, calcitriol, calcium, phosphate, and urinary fractional excretion of phosphate (Fe(PO4)) were measured in 80 CKD patients. Multiple linear regression was used to test the hypotheses. FGF-23 and PTH were inversely associated with estimated GFR (eGFR), whereas calcitriol levels were linearly associated with eGFR. Hyperphosphatemia and hypocalcemia were present in only 12 and 6% of patients, respectively, all of whose eGFR was <30. Increased Fe(PO4) was associated with decreased eGFR, and both increased FGF-23 and PTH were independently associated with increased Fe(PO4). Increased FGF-23 and decreased 25(OH)D3 were independent predictors of decreased calcitriol, but the effects on calcitriol levels of renal function itself and hyperphosphatemia were completely extinguished by adjusting for FGF-23. It is concluded that FGF-23 levels increase early in CKD before the development of serum mineral abnormalities and are independently associated with serum phosphate, Fe(PO4), and calcitriol deficiency. Increased FGF-23 may contribute to maintaining normal serum phosphate levels in the face of advancing CKD but may worsen calcitriol deficiency and thus may be a central factor in the early pathogenesis of SHPT.

• Authors: Orlando Gutierrez, Tamara Isakova, Eugene Rhee, Anand Shah, Julie Holmes, Gina Collerone, Harald Jüppner, Myles Wolf
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 16 Issue 7 Pg. 2205-15 (Jul 2005) ISSN: 1046-6673 [Print] United States
• PMID: 15917335 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• FGF23 protein, human
• Fibroblast Growth Factors
• Fibroblast Growth Factor-23
• Calcitriol

Topics

• Adult
• Aged
• Aged, 80 and over
• Calcitriol (deficiency, metabolism)
• Chronic Disease
• Cross-Sectional Studies
• Female
• Fibroblast Growth Factor-23
• Fibroblast Growth Factors (metabolism)
• Humans
• Hyperparathyroidism, Secondary (etiology, metabolism)
• Kidney Diseases (complications, metabolism)
• Male
• Middle Aged
• Phosphorus Metabolism Disorders (metabolism)