Cinacalcet treatment and serum FGF23 levels in haemodialysis patients with secondary hyperparathyroidism.

BACKGROUND Elevated fibroblast growth factor 23 (FGF23) is associated with adverse clinical outcomes and development of secondary hyperparathyroidism (SHPT) refractory to active vitamin D. Cinacalcet hydrochloride is effective in treating SHPT, but little is known as to whether treatment with cinacalcet alters these levels and whether pretreatment FGF23 levels predict response to this therapy. METHODS We measured serum full-length FGF23 levels in 55 haemodialysis patients, who participated and completed the 52-week, multicentre, open-label single-arm trial that examined the effectiveness of cinacalcet for treating SHPT. In the study, alteration of vitamin D dosage was not permitted except for the case in which serum calcium could not be managed by calcium carbonate adjustment alone. RESULTS After 12 weeks of cinacalcet treatment, FGF23 levels decreased significantly concomitantly with a significant reduction in intact parathyroid hormone (PTH) levels. These responses were sustained >52 weeks. In multivariate regression analyses, changes from baseline in serum FGF23 were associated with changes in serum calcium and phosphorus but not with intact PTH at each time point of measurements (Week-12, Week-24 and Week-52). Baseline FGF23 was not associated with the likelihood of achieving an intact PTH <180 pg/mL at the study end. CONCLUSIONS Cinacalcet lowers serum FGF23 in haemodialysis patients with SHPT independently of the effects of active vitamin D. Pretreatment FGF23 cannot predict treatment response to cinacalcet in this setting. The precise mechanism of FGF23 reduction by cinacalcet and its clinical impact on outcomes in patients remain to be investigated.