FGF23 and Cardiovascular Structure and Function in Advanced Chronic Kidney Disease.

Background: Fibroblast growth factor 23 (FGF23) is a bone-derived phosphatonin that is elevated in chronic kidney disease (CKD) and has been implicated in the development of cardiovascular disease. It is unknown whether elevated FGF23 in CKD is associated with impaired cardiovascular functional capacity, as assessed by maximum exercise oxygen consumption (VO ₂ Max). We sought to determine whether FGF23 is associated with cardiovascular functional capacity in patients with advanced CKD and after improvement of VO ₂ Max by kidney transplantation.
Methods: We performed secondary analysis of 235 patients from the Cardiopulmonary Exercise Testing in Renal Failure and After Kidney Transplantation (CAPER) cohort, which recruited patients with stage 5 CKD who underwent kidney transplantation or were waitlisted and hypertensive controls. All patients underwent cardiopulmonary exercise testing (CPET) and echocardiography and were followed longitudinally for 1 year after study enrollment.
Results: Patients across FGF23 quartiles differed in BMI ( P =0.004) and mean arterial pressure ( P <0.001) but did not significantly differ in sex ( P =0.5) or age ( P =0.08) compared with patients with lower levels of FGF23. Patients with higher FGF23 levels had impaired VO ₂ Max (Q1: 24.2±4.8 ml/min per kilogram; Q4: 18.6±5.2 ml/min per kilogram; P <0.001), greater left ventricular mass index (LVMI; P <0.001), reduced HR at peak exercise ( P <0.001), and maximal workload ( P <0.001). Kidney transplantation conferred a significant decline in FGF23 at 2 months ( P <0.001) before improvement in VO ₂ Max at 1 year ( P =0.008). Multivariable regression modeling revealed that changes in FGF23 was significantly associated with VO ₂ Max in advanced CKD ( P <0.001) and after improvement after kidney transplantation ( P =0.006). FGF23 was associated with LVMI before kidney transplantation ( P =0.003), however this association was lost after adjustment for dialysis status ( P =0.4). FGF23 was not associated with LVMI after kidney transplantation in all models.
Conclusions: FGF23 levels are associated with alterations in cardiovascular functional capacity in advanced CKD and after kidney transplantation. FGF23 is only associated with structural cardiac adaptations in advanced CKD but this was modified by dialysis status, and was not associated after kidney transplantation.
Competing Interests: A. Halim reports ownership interest in OVIBIO Corp. T.F. Hiemstra reports being an employee of GlaxoSmithKline; ownership interest in GlaxoSmithKline, Kodika Corp., and OVIBIO Corp.; research funding from UNION Therapeutics; and an advisory or leadership role for the International Clinical Trial Centre Network (SAB member) and the PHOSPHATE Trial (steering board member). S. Kalim reports participation in a speakers’ bureau for Fresenius Kabi. X. Li reports an advisory or leadership role for Health Services and Outcomes Research Methodology (member of editorial board 2014–present) and Circulation: Cardiovascular Quality and Outcomes (associated statistical editor 2016–present). K. Lim reports consultancy for Ambassadors Corp., MBX Biosciences, and OVIBIO Corp.; ownership interest in Ambassadors Corp., MBX Biosciences, and OVIBIO Corp.; and an advisory or leadership role for Ambassadors Corp. T. Lu reports consultancy for OVIBIO Corp. and ownership interest in OVIBIO Corp. S. Moe reports consultancy for Amgen, Ardelyx, and Sanifit; ownership interest in Eli Lilly (stock); research funding from Chugai (research grant), Keryx (research grant), and the National Institutes of Health (research grant); honoraria from Amgen, Ardelyx, and Sanifit; and an advisory or leadership role for the American Journal of Nephrology and the American Journal of Nutrition (editorial board). A.M. Siedlecki reports research funding from Alexion, and an advisory or leadership role for Alexion. R. Thadhani reports consultancy for Alnylum, Bayer, the US Food and Drug Administration, Fresenius Medical Care North America, Kaneka, and Thermo Fisher Scientific; ownership interest in Aggamin LLC, Comanche Pharma, Hero Health, and Tvardi; research funding from Thermo Fisher Scientific; honoraria from Alnylum, Bayer, and Thermo Fisher Scientific; patents or royalties from Gravidas Diagnostics, Thermo Fisher Scientific, and UpToDate; and an advisory or leadership role for Aggamin LLC and Vifor Pharma. D. Zehnder reports research funding for Abbott Laboratories and Amgen, and honoraria from Abbott Laboratories and Amgen. All remaining authors have nothing to disclose.
(Copyright © 2022 by the American Society of Nephrology.)