Parathyroid Hormone, Fibroblast Growth Factor 23, and Parameters of Phosphate Reabsorption

Abstract

Background: The serum phosphorus concentration ([P]s) is the sum of EP/Ccr and TRP/Ccr, where Ccr is creatinine clearance and EP and TRP are rates of excretion and reabsorption of phosphate. In chronic kidney disease (CKD), parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) mediate reduction of TRP/Ccr, and [PTH] and [FGF23] are linear functions of EP/Ccr. If controls and patients with CKD are considered together, TRP/Ccr is a hyperbolic function of EP/Ccr. Given these observations, we hypothesized that hyperbolas would describe relationships of phosphate reabsorption to [PTH] and [FGF23]. Methods: We studied 30 patients and 28 controls with mean eGFR of 29.5 and 86.0 mL/min/1.73 m2, respectively. All analyses combined both subsets. We measured fasting [PTH] 1–84 and intact [FGF23], and determined contemporaneous EP/Ccr, TRP/Ccr, fractional excretion of phosphorus (FEP), and phosphate tubular maximum per volume of filtrate (TmP/GFR). We examined linear regressions of TRP/Ccr and TmP/GFR on 100/[PTH] and 100/[FGF23]; from linear equations we derived hyperbolic equations relating reabsorptive parameters to hormone concentrations. Results: TRP/Ccr and TmP/GFR were linear functions of 100/[PTH] and 100/[FGF23] and hyperbolic functions of [PTH] and [FGF23]. TRP/Ccr and TmP/GFR fell minimally over the ranges of EP/Ccr, [PTH], and [FGF23] seen in CKD. FEP rose with EP/Ccr despite stable phosphate reabsorption. Conclusions: Hyperbolas describe relationships of TRP/Ccr and TmP/GFR to [PTH] and [FGF23] if subjects with normal and reduced GFR are analyzed together. Although FEP rises with [PTH] and [FGF23] as GFR falls, the simultaneous increments do not signify hormonally mediated reductions in phosphate reabsorption.