Elevated Glycerol-3-Phosphate in Patients Undergoing Hemodialysis: Associations with Phosphate and Fibroblast Growth...

Fibroblast growth factor 23 (FGF23) levels are markedly elevated in patients with kidney failure, but the mechanisms are incompletely understood. Recent evidence suggests that kidney-derived glycerol-3-phosphate (G-3-P), a glycolytic byproduct, mediates FGF23 production in response to dietary phosphate loading. However, the role of G-3-P is unknown in patients with kidney failure.

Serum G-3-P levels were quantified by LC/MS in 35 healthy individuals and 650 patients undergoing hemodialysis. Association between serum phosphorus and G-3-P was examined using unadjusted and multivariable linear regression models. We next analyzed the associations of G-3-P and known regulators of FGF23 production with serum FGF23.

Median serum G-3-P level in patients undergoing hemodialysis was 220 ng/mL (IQR, 118-325), 2.2-fold higher than that of healthy individuals (98 ng/mL; IQR, 80-129). In patients undergoing hemodialysis, higher serum phosphorus was strongly associated with increased G-3-P in the unadjusted model; this association persisted after multivariate adjustment and when restricted to patients undergoing hemodialysis for over 10 years. In univariate analyses, higher serum phosphorus, calcium, intact PTH, G-3-P, and active vitamin D use were each significantly associated with higher FGF23. Multivariate analysis identified G-3-P as an independent predictor of FGF23. Further adjustment for transferrin saturation, ferritin, and C-reactive protein did not change these findings.

Even in patients with kidney failure, G-3-P may rise in response to phosphate retention and act as a regulator of FGF23 production. Further studies are needed to test these hypotheses and determine whether the apparently nonfunctioning kidney retains the capacity to produce G-3-P.