Chronic kidney disease affects 11% of the US population; over half of those affected have skeletalmanifestations of their renal disease. Renal osteodystrophy is a complex disease, in which multiple mineralsystems and related hormones play a role, including phosphate homeostasis. Phosphate regulationprimarily depends on renal handling of phosphate, which is partly controlled by parathyroid hormone andvitamin D. However, other mediators in this system clearly exist. Recently, evidence has been accruing thatone factor may be FGF23, a protein produced by osteogenic cells. States of excess FGF23 are associatedwith marked phosphate wasting, hypophosphatemia, osteomalacia, and inappropriately low calcitriol. FGF2_levels are measurable in healthy humans and markedly elevated in patients who require hemodialysis,although its physiologic role in either state is unknown. Some retrospective evidence suggests that FGF23is affected by phosphate intake. We propose the first study designed to examine phosphorus intake andFGF23 in a prospective trial and to determine the effects of dietary phosphate on FGF23 in the setting ofmoderate renal insufficiency.
The specific aims of the research project are to determine: 1) The physiologiceffects of alterations in dietary phosphorus on FGF23 in healthy subjects; 2) The physiologic response ofFGF23 to dietary phosphorus alterations in patients with moderate renal failure; and 3) Whether serum level.,of 1,25-dihydroxyvitamin D vary inversely with those of FGF23 when dietary phosphate is changed. Acomplementary objective of this proposal is to support the development of the applicant into an independentclinical investigator in renal osteodystrophy through the pursuit of a Master's in Clinical Research, directmentoring, and supervised research at the General Clinical Research Center. The proposed research planis a dietary intervention trial in which we will study the response of serum FGF23 levels to diets with varying)hosphorus contents in 16 healthy adults and 16 adults with moderate renal insufficiency.
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| Antoniucci, Diana M; Sellmeyer, Deborah E; Bilezikian, John P et al. (2007) Elevations in serum and urinary calcium with parathyroid hormone (1-84) with and without alendronate for osteoporosis. J Clin Endocrinol Metab 92:942-7 |
| Ensrud, Kristine E; Lui, Li-Ying; Taylor, Brent C et al. (2007) Renal function and risk of hip and vertebral fractures in older women. Arch Intern Med 167:133-9 |
| Antoniucci, Diana M; Yamashita, Takeyoshi; Portale, Anthony A (2006) Dietary phosphorus regulates serum fibroblast growth factor-23 concentrations in healthy men. J Clin Endocrinol Metab 91:3144-9 |
