The Effect of Caloric Restriction and Aerobic Exercise on Serum FGF-23 in Patients with Moderate to Severe CKD

BACKGROUND Chronic kidney disease (CKD) is associated with elevated serum fibroblast growth factor 23 (FGF23) which correlates with increased cardiovascular risk. Prior data suggest serum FGF23 is also associated with increased adiposity. We tested the hypothesis that an intervention involving caloric restriction and aerobic exercise to reduce body weight would reduce serum FGF23 in patients with moderate to severe CKD. METHODS We performed a secondary analysis of data from a 2Χ2 factorial randomized trial enrolling 103 participants randomized to receive combined caloric restriction and aerobic exercise, caloric restriction alone, aerobic exercise alone, or usual care. Enrollees were persons with a median estimated glomerular filtration rate (eGFR) of 40.5 ml/min/1.73m2 (IQR: 30.3, 56.2). Measurements of Serum FGF23 (using C-terminal ELISA assay) and serum phosphate were obtained at baseline and month 4. Changes in serum FGF23 between baseline and month 4 across intervention arms were examined using analysis of covariance with robust standard errors. RESULTS After adjustment for baseline differences, serum FGF23 levels fell by 20.6% [95%CI: 0.4, 36.7, p = 0.047] more in the combined intervention arm compared to usual care. Further adjustment for baseline serum phosphate attenuated the relative difference in serum FGF23 decline between the combined intervention arm and usual care [percent change = -18.6, 95% CI: -35.3, 2.9; p = 0.10]. Caloric restriction or exercise alone did not demonstrate significantly greater decline in serum FGF23 compared to usual care. The median values of change in serum phosphate between baseline and month 4 among participants in the combined intervention and diet-only arms were -0.15 and 0.05 mg/dl whereas the exercise and usual care arms experienced no change in serum phosphate. Neither intervention arm showed a significantly greater percent change in serum phosphate from baseline to month 4 compared to usual care. CONCLUSION A combined 4-month calorie restriction and aerobic exercise intervention led to significant reductions in serum FGF23. The magnitude of serum FGF23 reduction appeared to be influenced in part by baseline serum phosphate levels while the latter remained relatively unchanged at the end of the trial. Funding Other NIH Suppor