Kidney Week

Abstract: FR-PO297

Glycerol-3-Phosphate Is an Independent Predictor of FGF23 Levels in Hemodialysis Patients

Session Information

• Bone and Mineral Metabolism: Basic
  November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Bone and Mineral Metabolism

• 502 Bone and Mineral Metabolism: Clinical

Authors

• Nakagawa, Yosuke, Tokai Daigaku Igakubu Jin Naibunpi Taisha Naika, Isehara, Kanagawa, Japan

Yosuke Nakagawa,

• Komaba, Hirotaka, Tokai Daigaku Igakubu Jin Naibunpi Taisha Naika, Isehara, Kanagawa, Japan

Hirotaka Komaba,

• Ito, Masatoshi, Sei Marianna Ika Daigaku, Kawasaki, Kanagawa, Japan

Masatoshi Ito,

• Ishioka, Chigusa, Tokai Daigaku Igakubu Jin Naibunpi Taisha Naika, Isehara, Kanagawa, Japan

Chigusa Ishioka,

• Hamano, Naoto, Tokai Daigaku Igakubu Jin Naibunpi Taisha Naika, Isehara, Kanagawa, Japan

Naoto Hamano,

• Tomita, Yusuke, Tokai Daigaku Igakubu Daigakuin Igaku Kenkyuka, Isehara, Kanagawa, Japan

Yusuke Tomita,

• Nakamura, Michio, Tokai Daigaku Igakubu Daigakuin Igaku Kenkyuka, Isehara, Kanagawa, Japan

Michio Nakamura,

• Kakuta, Takatoshi, Tokai Daigaku Igakubu Fuzoku Hachioji Byoin, Hachioji, Tokyo, Japan

Takatoshi Kakuta,

• Fukagawa, Masafumi, Tokai Daigaku Igakubu Jin Naibunpi Taisha Naika, Isehara, Kanagawa, Japan

Masafumi Fukagawa,

Background

FGF23 levels are markedly elevated in kidney failure, but the mechanisms for the increased FGF23 production is incompletely understood. Emerging evidence shows that kidney-derived glycerol-3-phosphate (G-3-P), a byproduct of glycolysis, serves as a key mediator of FGF23 production in response to dietary phosphate loading. However, little is known about the role of G-3-P in kidney failure.

Methods

We measured serum G-3-P levels by LC/MS in 35 healthy individuals and 650 hemodialysis (HD) patients enrolled in the Tokai Dialysis Prospective Cohort Study. We employed multivariable linear regression to explore whether hyperphosphatemia is associated with increased G-3-P levels in HD patients. We next examined whether serum G-3-P is a determinant of FGF23 levels, independent of known regulators of FGF23 such as serum phosphorus, calcium, PTH, iron metabolism, and inflammation.

Results

The median serum G-3-P level in HD patients was 220 ng/mL (interquartile range [IQR], 118-325 ng/mL), which was 2.2-fold higher than that in healthy individuals (98 ng/mL; IQR, 80-129 ng/mL; P < 0.001). Patients with higher G-3-P were younger; were more likely to be male; were less likely to have diabetes; had higher body mass index and higher serum albumin, creatinine, phosphorus, and total cholesterol; and were more often prescribed calcium carbonate and cinacalcet. Higher serum phosphorus was strongly associated with higher G-3-P; this association was unchanged after multivariate adjustment and was significant even when the analysis was restricted to patients undergoing dialysis for more than 10 years. In univariate analyses, higher serum phosphorus, calcium, intact PTH, and G-3-P, and active vitamin D use were each significantly associated with higher FGF23. In multivariate analyses, G-3-P was identified as one of the independent predictors of FGF23. Further adjustment fortransferrin saturation, ferritin, and C-reactive protein did not qualitatively change these findings.

Conclusion

These findings suggest that even in patients with kidney failure, G-3-P is increased by phosphate retention and serve as a regulator of FGF23 production. Additional studies are needed to test these hypotheses and to explore whether the apparently non-functioning kidney still has the capacity to produce G-3-P.