Chronic kidney disease affects 11% of the US population; over half of those affected have skeletal manifestations of their renal disease. Renal osteodystrophy is a complex disease, in which multiple mineral systems and related hormones play a role, including phosphate homeostasis. Phosphate regulation primarily depends on renal handling of phosphate, which is partly controlled by parathyroid hormone and vitamin D. However, other mediators in this system clearly exist. Recently, evidence has been accruing that one factor may be FGF23, a protein produced by osteogenic cells. States of excess FGF23 are associated with marked phosphate wasting, hypophosphatemia, osteomalacia, and inappropriately low calcitriol. FGF23 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 FGF23 is affected by phosphate intake. We propose the first study designed to examine phosphorus intake and FGF23 in a prospective trial and to determine the effects of dietary phosphate on FGF23 in the setting of moderate renal insufficiency.
The specific aims of the research project are to determine: 1) The physiologic effects of alterations in dietary phosphorus on FGF23 in healthy subjects; 2) The physiologic response of FGF23 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. A complementary objective of this proposal is to support the development of the applicant into an independent clinical investigator in renal osteodystrophy through the pursuit of a Master's in Clinical Research, direct mentoring, and supervised research at the General Clinical Research Center. The proposed research plan is a dietary intervention trial in which we will study the response of serum FGF23 levels to diets with varying phosphorus contents in 16 healthy adults and 16 adults with moderate renal insufficiency.
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| 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 |
