The FGF-23/klotho axis and its relationship with phosphorus, calcium, vitamin D, PTH, aldosterone, severity of disease, and outcome in hospitalised foals.
Authors: Kamr A M, Dembek K A, Hildreth B E, Morresey P R, Rathgeber R A, Burns T A, Zaghawa A A, Toribio R E
Journal: Equine veterinary journal
Summary
# Editorial Summary: FGF-23/Klotho Axis in Hospitalised Foals Mineral and endocrine dysregulation characterises critical illness in neonatal foals, yet the role of fibroblast growth factor-23 (FGF-23) and its co-receptor klotho in this context remained poorly understood until this 2018 multicentre investigation. Researchers measured serum FGF-23, klotho, phosphorus, calcium, vitamin D metabolites (25(OH)D and 1,25(OH)₂D), parathyroid hormone (PTH), and aldosterone in 81 hospitalised foals (58 septic, 23 sick non-septic) and 10 healthy neonates, finding that septic and sick foals exhibited elevated FGF-23, PTH, and phosphorus alongside depressed klotho, vitamin D metabolites, and total calcium compared to healthy controls. Of particular prognostic significance, foals with the highest FGF-23 concentrations carried a 3.3-fold increased mortality risk, whilst those with the lowest klotho concentrations faced a 3.1-fold increased risk, suggesting FGF-23 resistance may accelerate disease progression. The patterns observed—elevated FGF-23 and aldosterone coupled with high phosphorus and PTH but normal calcium—indicate that mineral dysregulation in critically ill foals involves dysaxis of the FGF-23/klotho system and warrant routine serum phosphorus monitoring as part of neonatal foal assessment, with FGF-23 and klotho potentially serving as non-invasive biomarkers of illness severity and prognostic indicators for clinical decision-making.
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Practical Takeaways
- •Measure serum phosphorus routinely in sick foals as part of disease assessment and severity monitoring
- •FGF-23 and klotho concentrations may serve as prognostic biomarkers for mortality risk in hospitalised neonatal foals
- •Monitor mineral metabolism comprehensively in septic foals, as imbalances in the FGF-23/klotho axis contribute to disease progression and critical illness
Key Findings
- •Septic and sick non-septic foals had significantly higher FGF-23, PTH, and phosphorus but lower klotho, 25(OH)D, 1,25(OH)2D, and total calcium compared to healthy foals
- •Foals with highest FGF-23 concentrations had 3.3-fold increased odds of mortality; those with lowest klotho had 3.1-fold increased odds of mortality
- •FGF-23 resistance was evidenced by elevated FGF-23 and reduced klotho despite high phosphorus and PTH concentrations
- •Aldosterone concentrations were associated with phosphorus and PTH dynamics in hospitalised foals