Regulation of fibroblast growth factor 23 production in bone in uremic rats

Abstract

Background: Fibroblast growth factor 23 (FGF23) regulates renal phosphate reabsorption and 1alpha,25-dihydroxyvitamin D [1,25(OH)(2)D(3)] metabolism. Patients with chronic kidney disease (CKD) have increased levels of circulating FGF23, but the direct regulation of this elevation of FGF23 is incompletely understood.

Method: We measured plasma parameters in uremic rats fed a high-phosphorus diet and then performed parathyroidectomy (PTX) to determine its effect. We also investigated FGF23 mRNA expression in various tissues to identify the major source of circulating FGF23.

Result: The uremic rats displayed dramatic changes in plasma FGF23 levels, consistent with increased expression of FGF23 in bone. Elevated FGF23 was associated with phosphate and parathyroid hormone (PTH). After PTX, the elevated FGF23 had decreased, consistent with decreased expression of FGF23 in bone. Significant decreases in plasma FGF23 were associated with PTH and 1,25(OH)(2)D(3), but not phosphate.

Conclusion: Elevated plasma FGF23 levels in uremic rats reflect the increased expression of FGF23 in bone. The expression of FGF23 in bone may be regulated by a PTH-1,25(OH)(2)D(3) axis-dependent pathway and another PTH-dependent and 1,25(OH)(2)D(3)-independent pathway in uremic rats. The pathway may be decided by the degree of renal dysfunction.