Abstract: FR-PO165
Interaction Between FGF-23 and Soluble Klotho on Cardiovascular Events in Patients Receiving Hemodialysis
Session Information
- Bone and Mineral Metabolism: Phosphorus, FGF23, Vascular Calcification
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 402 Bone and Mineral Metabolism: Clinical
Authors
- Tanaka, Hisae, Tokai University School of Medicine, Isehara, Japan
- Komaba, Hirotaka, Tokai University School of Medicine, Isehara, Japan
- Ishida, Hiroaki, Tokai University School of Medicine, Isehara, Japan
- Takahashi, Hiroo, Tokai University School of Medicine, Isehara, Japan
- Wada, Takehiko, Tokai University School of Medicine, Isehara, Japan
- Kakuta, Takatoshi, Tokai University School of Medicine, Isehara, Japan
- Nakamura, Michio, Tokai University School of Medicine, Isehara, Japan
- Takahashi, Yuichiro, Jinken Clinic, Ebina, Japan
- Hyodo, Toru, Kurata Hospital, Hiratsuka, Japan
- Hida, Miho, Kurata Hospital, Hiratsuka, Japan
- Fukagawa, Masafumi, Tokai University School of Medicine, Isehara, Japan
Background
Membrane Klotho binds to FGFR1 and forms a specific receptor for FGF23. Recent investigations have demonstrated that soluble Klotho, a cleavage product of membrane Klotho, also mediates FGF23-dependent bioactivity. Elevated FGF23 may have detrimental effects on several tissues that do not express membrane Klotho. It is not known whether this process is mediated through the binding of soluble Klotho to FGFR1 and FGF23.
Methods
We conducted a 3-year prospective cohort study of 654 maintenance hemodialysis patients. We examined the interaction between FGF23 and soluble Klotho for the composite of all-cause mortality and cardiovascular events using multivariate Cox regression.
Results
During the follow-up period, 103 patients reached the primary composite endpoint. After adjustments for confounding, elevated FGF23 was independently associated with a higher risk of the primary composite end point only in patients with soluble Klotho greater than the median value (HR per doubling, 1.20; 95% CI, 1.04-1.39; P=0.005 for interaction). Likewise, elevated soluble Klotho was associated with a higher risk of the primary composite end point only in patients with FGF23 greater than the median value (HR per 100 pg/ml increase, 1.25; 95% CI, 1.08-1.46; P=0.005 for interaction). When we categorized the patients into 4 groups according to their medians of FGF23 and soluble Klotho, the highest risk for the primary composite endpoint was observed in patients with high FGF23 and high soluble Klotho.
Conclusion
These data suggest that elevated levels of FGF23 and soluble Klotho contribute to cardiovascular disease in a coordinated manner.
Funding
- Commercial Support – Roche Diagnostics K.K. (Tokyo, Japan)