Kidney Week 2025 Annual Meeting-Novel Therapeutic Approaches and Pathways for Phosphate and Fibroblast Growth Factor 23 Regulation

Video Transcription

Video Summary

The session, moderated by nephrologists Daniel Edmundson and Wei Chen, focused on new mechanisms and potential therapies to regulate phosphate and FGF23 in kidney disease.<br /><br />Michaela Fuchs presented work on tissue-specific vitamin D degradation via CYP24A1. Using new inducible, kidney-specific, and intestine-specific CYP24A1 knockout mice, her group showed that kidney CYP24A1 primarily controls circulating active vitamin D, while intestinal CYP24A1 controls local intestinal vitamin D action. Intestinal CYP24A1 deletion suppressed PTH without raising serum calcium or systemic vitamin D, partly by increasing calcium absorption and urinary calcium excretion. In an adenine CKD model, intestinal CYP24A1 deletion reduced rises in both PTH and FGF23, suggesting a possible safer approach to secondary hyperparathyroidism than systemic vitamin D analogs, though long-term effects (e.g., vascular calcification) need study.<br /><br />Petra Simic described a kidney-to-bone signaling pathway where glycerol-3-phosphate (G3P), released from injured kidneys, is converted in bone to lysophosphatidic acid (LPA) via GPAT2, stimulating FGF23. Osteoblast GPAT2 knockout reduced FGF23 and unexpectedly lowered phosphate by enhancing fatty-acid–driven osteoblast mineralization and phosphate incorporation. In CKD mice, GPAT2 knockout improved bone formation, reduced vascular calcification and cardiac hypertrophy, “uncoupling” phosphate from FGF23.<br /><br />Daniela Egli-Schvigtig showed that in AKI, hyperphosphatemia and high FGF23 associate with worse outcomes. In folic-acid AKI mice, dietary phosphate restriction reduced phosphate, FGF23, inflammation (IL-6), calciprotein particles, acidosis, electrolyte disturbances, QT prolongation, and mortality.<br /><br />Makoto Kuro-o detailed calciprotein monomers/particles (CPM/CPP): CPM can induce FGF23, while CPP promotes inflammation, calcification, and tissue injury. A CPP-adsorbing dialysis column improved survival and reduced calcification and inflammation in nephrectomized pigs. He proposed a vicious cycle where elevated FGF23 increases tubular phosphate, promoting CPP formation in urine and tubular injury, accelerating CKD progression, supporting earlier phosphate-lowering/CPP-inhibiting strategies.

Asset Subtitle

Moderator(s): Wei Chen, Daniel Edmonston

Presentation(s):

Differential Impacts of Intestinal vs. Renal Vitamin D Metabolism - Michaela Fuchs
Glycerol-3-Phosphate Metabolism in CKD-MBD - Petra Simic
Phosphate Restriction and AKI - Daniela Egli-Spichitg
Calciprotein Particles in CKD and Its Complications - Makoto Kuro-o

Meta Tag

Date 11/6/2025

Pathway 1 Bones, Stones, and Mineral Metabolism

Session ID 507251

Keywords

phosphate regulation

FGF23

chronic kidney disease (CKD)

acute kidney injury (AKI)

CYP24A1

tissue-specific vitamin D degradation

intestinal CYP24A1 knockout

kidney CYP24A1 knockout

secondary hyperparathyroidism

parathyroid hormone (PTH)

glycerol-3-phosphate (G3P)

lysophosphatidic acid (LPA)

GPAT2

vascular calcification

calciprotein particles (CPP/CPM)