Exploring FGF23 Regulation in Kidney Failure

Exploring FGF23 Regulation in Kidney Failure – Fibroblast growth factor 23 (FGF23) is a key hormone that is involved in the regulation of mineral metabolism, particularly regulating phosphate balance (1). In patients with end-stage kidney disease (ESKD), circulating FGF23 levels are markedly elevated and have been independently associated with increased mortality (2). However, the mechanisms driving this rise in FGF23 are not yet fully understood.

Exploring FGF23 Regulation in Kidney Failure

Glycerol-3-phosphate (GP) is a a glycolysis-derived metabolite that may originate from injured kidneys. It has been suggested to stimulate FGF23 production and may therefore play a role in the phosphate–FGF23 axis in kidney disease (3). To investigate this further, researchers explored the relationship between kidney-derived G3P, phosphate, and FGF23 in patients undergoing hemodialysis (4) :

Elevated Glycerol-3-Phosphate in Patients Undergoing Hemodialysis: Associations with Phosphate and Fibroblast Growth Factor 23. Nakagawa Y et al. 2025.

The BIOMEDICA FGF23 (C-terminal) ELISA assay (cat. no. BI-20702) was successfully used in this study.

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

FGF23 (C-terminal) ELISA , cat no. BI-20702

• RELIABLE – validated following international quality guidelines
• TRUSTED – cited in over 75 publications
• EASY – 8 standards and 2 controls included
• FLEXIBLE – For SERUM & PLASMA samples

 Protocol Booklet – link

Related products: FGF23 intact ELISA, cat. no. BI-20700

Learn more about FGF23 – FGF23 an overview

Literature:

1. FGF23: A Review of Its Role in Mineral Metabolism and Renal and Cardiovascular Disease. Kurpas A, Supeł K, Idzikowska K, Zielińska M.Dis Markers. 2021 May 17;2021:8821292. doi: 10.1155/2021/8821292. PMID: 34055103; PMCID: PMC8149241.
2. Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. Isakova T, Xie H, Yang W, Xie D, Anderson AH, Scialla J, Wahl P, Gutiérrez OM, Steigerwalt S, He J, Schwartz S, Lo J, Ojo A, Sondheimer J, Hsu CY, Lash J, Leonard M, Kusek JW, Feldman HI, Wolf M; Chronic Renal Insufficiency Cohort (CRIC) Study Group. JAMA. 2011 Jun 15;305(23):2432-9. doi: 10.1001/jama.2011.826. PMID: 21673295; PMCID: PMC3124770.
3. Association between Serum Glycerol-3-Phosphate and Fibroblast Growth Factor-23 in Nondiabetic Patients on Hemodialysis. Wilson SM, Zaslow S, Sozio SM, Jaar BG, Perwad F, Robinson-Cohen C, Estrella MM, Martin A, Parekh RS, Chen W. Clin J Am Soc Nephrol. 2026 Feb 1;21(2):211-220. doi: 10.2215/CJN.0000000871. Epub 2025 Oct 17. PMID: 41105473; PMCID: PMC12737521.
4. Elevated Glycerol-3-Phosphate in Patients Undergoing Hemodialysis: Associations with Phosphate and Fibroblast Growth Factor 23. Nakagawa Y, Ito M, Tomita Y, Nakamura M, Shimamura N, Takahashi H, Takahashi Y, Hyodo T, Hida M, Suga T, Kakuta T, Komaba H. Am J Nephrol. 2025 Dec 17:1-9. doi: 10.1159/000550130. Epub ahead of print. PMID: 41406040.