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

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.

We studied 29 patients with CKD at 4 visits and 28 controls at 1 visit. Assuming GFR = creatinine clearance (Ccr), we examined the following regressions: [P]s on its determinants, EP/Ccr and TRP/Ccr (P excretion and reabsorption per volume of filtrate); [PTH] and [FGF23] on [P]s and EP/Ccr; and TRP/Ccr on [PTH] and [FGF23]. We assumed that EP/Ccr is proportional to [P]f in the CDN.

In controls, [P]s correlated with TRP/Ccr but not EP/Ccr. [PTH] and [FGF23] were unrelated to [P]s, EP/Ccr, and TRP/Ccr. In CKD, [P]s correlated with EP/Ccr and TRP/Ccr. [PTH] correlated with [P]s at 2 visits and with EP/Ccr at 4; [FGF23] correlated with [P]s and EP/Ccr at all visits. TRP/Ccr correlated with [FGF23] and [PTH] at one visit each.

[P]f in the CDN, not [P]s, determined [PTH] in CKD. Because [FGF23] was consistently associated with only one determinant of [P]s, EP/Ccr, 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.