Phosphate homeostasis, parathyroid hormone, and fibroblast growth factor 23 in stages 3 and 4 chronic kidney disease

Aims: Increased concentrations of parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) often coincide with normal serum phosphorus ([P](s)) in chronic kidney disease (CKD). We hypothesized that the phosphate concentration ([P](f)) in the cortical distal nephron (CDN) determines [PTH] and [FGF23] in this circumstance. Methods: We studied 29 patients with CKD at 4 visits and 28 controls at 1 visit. Assuming GFR = creatinine clearance (C-cr), we examined the following regressions: [P](s) on its determinants, E-P/C-cr and TRP/C-cr (P excretion and reabsorption per volume of filtrate); [PTH] and [FGF23] on [P] s and E-P/C-cr; and TRP/C-cr on [PTH] and [FGF23]. We assumed that E-P/C-cr is proportional to [P](f) in the CDN. Results: In controls, [P](s) correlated with TRP/C-cr but not E-P/C-cr. [PTH] and [FGF23] were unrelated to [P](s), E-P/C-cr, and TRP/C-cr. In CKD, [P](s) correlated with E-P/C-cr and TRP/C-cr. [PTH] correlated with [P](s) at 2 visits and with E-P/C-cr at 4; [FGF23] correlated with [P](s) and E-P/C-cr at all visits. TRP/C-cr correlated with [FGF23] and [PTH] at one visit each. Conclusions: [P](f) in the CDN, not [P](s), determined [PTH] in CKD. Because [FGF23] was consistently associated with only one determinant of [P](s), E-P/C-cr, we infer that [P](f) also determined [FGF23]. In patients with CKD, we speculate that [P](f) in the CDN regulates FGF23 synthesis at that site.