Lin Hsin-Hung, Liou Hung-Hsiang, Wu Ming-Shiou, Lin Ching-Yuang, Huang Chiu-Ching
The Kidney Institute and Division of Nephrology, China Medical University Hospital, Taichung, Taiwan; Graduate Institute of Clinical Medical Science, College of Medicine, China Medical University, Taichung, Taiwan.
Nephrology (Carlton). 2014 Nov;19(11):672-8. doi: 10.1111/nep.12319.
Fibroblast 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.
In 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.
After 48-week sevelamer treatment, there were significant changes with lower LDL-C (from 2.82 ± 0.78 to 1.65 ± 0.53 mmol/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 (β = -0.277, P = 0.005), change of serum phosphate (β = 0.609, P = 0.000) and calcium levels (β = 0.635, P = 0.000). The increase of serum Klotho was associated with the decrease of serum phosphate (β = 0.490, P = 0.019).
Maintenance 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.
成纤维细胞生长因子23(FGF23)和Klotho与透析患者的血管钙化及心血管疾病相关。已证实司维拉姆可减缓血管钙化进展。本研究旨在确定司维拉姆治疗对慢性血液透析(HD)患者血清FGF23和Klotho水平的长期影响。
在一项事后分析中,我们测量了50例完成了一项为期48周的开放标签、对照随机平行组研究的血液透析患者的血清FGF23、Klotho及其他生化指标(钙、磷、i-PTH、hsCRP、LDL-C)。23例患者接受司维拉姆治疗,27例患者接受碳酸钙治疗。
经过48周的司维拉姆治疗后,出现了显著变化,LDL-C降低(从2.82±0.78降至1.65±0.53 mmol/L,P = 0.000),FGF23降低(从2465.97(2568.88)降至795.61(1098.39),P = 0.000),可溶性Klotho水平升高(从189.35(161.88)升至252.94(517.80)pg/mL,P = 0.000)。在碳酸钙组中,LDL-C和FGF23无显著变化,但可溶性Klotho水平有临界显著升高(从142.34(265.24)升至188.57(252.38)pg/mL,P = 0.054)。多变量分析显示,FGF23降低与司维拉姆治疗相关(β = -0.277,P = 0.005),与血清磷的变化(β = 0.609,P = 0.000)及钙水平变化(β = 0.635,P = 0.000)相关。血清Klotho升高与血清磷降低相关(β = 0.490,P = 0.019)。
经过48周的司维拉姆治疗后,维持性血液透析患者的血清FGF23水平降低,同时血清Klotho水平显著升高。FGF23降低与司维拉姆的使用、血清磷和钙水平的变化相关。血清Klotho升高与结合剂的降磷能力成正比。