Long-term sevelamer treatment lowers serum fibroblast growth factor 23 accompanied with increasing serum Klotho levels in chronic haemodialysis patients

AimsFibroblast growth factor 23 (FGF23) and Klotho are associated with vascular calcification and cardiovascular disease in dialysis patients. Sevelamer has been shown to reduce progression of vascular calcification. This study aimed to determine the long-term effect of sevelamer treatment on serum FGF23 and Klotho levels in chronic haemodialysis (HD) patients. MethodsIn the post-hoc analysis, we measured serum FGF23, Klotho and other biochemical factors (Ca, P, i-PTH, hsCRP, LDL-C) in 50 haemodialysis patients, who completed a 48-week, open-Label, controlled randomized parallel-group study. Twenty-three patients received sevelamer and 27 patients received calcium carbonate. ResultsAfter 48-week sevelamer treatment, there were significant changes with lower LDL-C (from 2.820.78 to 1.650.53mmol/L, P=0.000), lower FGF23 (from 2465.97 (2568.88) to 795.61 (1098.39), P=0.000) and higher s-Klotho levels (from 189.35 (161.88) to 252.94 (517.80) pg/mL, P=0.000). In calcium carbonate group, there were no significant changes of LDL-C and FGF23, but with a borderline significant increase of s-Klotho level (from 142.34 (265.24) to 188.57 (252.38) pg/mL, P=0.054). Multivariate analysis showed that FGF23 decrement was associated with sevelamer treatment (=-0.277, P=0.005), change of serum phosphate (=0.609, P=0.000) and calcium levels (=0.635, P=0.000). The increase of serum Klotho was associated with the decrease of serum phosphate (=0.490, P=0.019). ConclusionMaintenance HD patients had lower serum FGF23 levels, accompanied with significantly increased serum Klotho levels, after 48-week sevelamer treatment. The FGF23 decrement was associated with sevelamer use, the change of serum phosphate and calcium levels. The serum Klotho increment was proportional to the phosphate-lowering power of the binders. Summary at a Glance Understanding fibroblast growth factor 23 (FGF23) and Klotho is of increasing interest to further evaluate phosphate homeostasis in kidney disease. Few studies have addressed potential interventions associated with changes in these regulators of phosphate. This study reports on an association of sevelamer with reducing FGF23 and increasing Klotho levels in dialysis.