Kidney to bone via bedside to bench…and back?

Area of Science:

• Nephrology
• Endocrinology
• Cardiovascular Medicine

Background:

• Elevated fibroblast growth factor 23 (FGF23) in kidney injury causes mineral imbalance and cardiovascular risks.
• The precise mechanisms driving FGF23 elevation during kidney injury are not fully understood.

Purpose of the Study:

• To elucidate the pathway linking kidney injury to increased FGF23 levels.
• To identify key molecular mediators involved in FGF23 regulation.

Main Methods:

• Screening of plasma from renal vein catheterization patients to identify FGF23 correlates.
• Administration of glycerol-3-phosphate (G-3-P) to mouse models.
• Investigating the role of lysophosphatidic acid (LPA) and its receptor in FGF23 production.

Main Results:

• Glycerol-3-phosphate (G-3-P) emerged as a significant correlate of arterial FGF23 levels.
• G-3-P administration increased FGF23 production in mouse bone.
• A pathway involving G-3-P, lysophosphatidic acid (LPA), and LPA receptor 1 was identified, stimulating FGF23 secretion from bone and bone marrow cells.

Conclusions:

• The study identifies a novel pathway (G-3-P/LPA/LPA receptor 1) contributing to FGF23 elevation in kidney injury.
• Human data broadly support the findings from mouse models.
• Further research is warranted to explore therapeutic targeting of this pathway for FGF23-related complications.