WIP 45 - FGF23 and CKD Progression Independent of Hyperphosphatemia: Insights from a Murine Model

Publication Number: WIP 45.7588

Mark R.. Hanudel, University of California, Los Angeles David Geffen School of Medicine, Los Angeles, CA, United States; Zenab Tamer, University of California, Los Angeles David Geffen School of Medicine, Los Angeles, CA, United States

Background: Chronic kidney disease (CKD) in children presents unique challenges, often leading to complications that affect growth, cardiovascular health, and overall quality of life. Understanding the molecular drivers of CKD progression in pediatrics is crucial for developing targeted therapies. One area of emerging interest is fibroblast growth factor 23 (FGF23), a hormone secreted from bone and involved in phosphate regulation. Elevated FGF23 levels are commonly associated with CKD and are linked to adverse outcomes, yet its role independent of hyperphosphatemia remains underexplored. This project aims to investigate the effects of FGF23 on CKD progression in abcense of elevated phosphate levels, providing insight into potential alternative molecular pathways that regulate FGF23. This project investigates FGF23's effects on CKD progression without elevated phosphate levels, potentially revealing alternative molecular pathways that regulate FGF23. The findings could inform new therapeutic approaches targeting FGF23 to mitigate its impact on CKD progression and other organs.

Objective: - To identify alternative molecular pathways influenced by FGF23 that contribute to CKD progression in the absence of hyperphosphatemia.
-To examine the direct effects of FGF23 on CKD progression, particularly in relation to fibrosis and inflammation, independent of phosphate regulation.
- To explore potential therapeutic targets within the FGF23 regulatory pathways that could slow CKD progression.

Design/Methods: We utilized murine models to investigate the role of FGF23 in CKD progression, comparing wild-type and inducible global Fgf23 knockout mice. Both wild-type and FGF23 KO mice were fed a low-phosphate diet to avoid the confounding effect of hyperphosphatemia on kidney fibrosis. On the other hand, control groups (both wild & FGF23 mice) fed standard phosphate diet. Mice were sacrificed at around ten weeks of age. Blood, serum, and tissues were collected to further analyze and measure serum creatinine, urea, phosphate, and FGF23 levels. Kidney tissues were stored.