血清c端成纤维细胞生长因子23水平与血液透析患者血管钙化严重程度及进展的相关性研究

Study on the correlation between the serum level of C-terminal fibroblast growth factor 23(cFGF23)and the severity and progression of vascular calcification in hemodialysis patients

目的探讨c端成纤维细胞生长因子23(c terminal fibroblast growth factor 23,cFGF23)和全段成纤维细胞生长因子23(intact fibroblast growth factor 23,iFGF23)水平与维持性血液透析(maintain hemodialysis,MHD)患者冠状动脉钙化(coronary artery calcium,CAC)严重程度及进展的相关性。方法收集2015年3月~2021年3月在首都医科大学附属北京安贞医院行MHD患者的基线资料及化验结果。ELISA法检测患者的血清cFGF23和iFGF23水平;计算机断层扫描检测冠状动脉钙化积分(coronary artery calcium score,CACs)情况。结果共37例患者行CAC检查。重度CAC组血清cFGF23水平高于非重度CAC组[1128.6(1073.2,1252.8)RU/ml比1036.9(927.7,1121.8)RU/ml,Z=-2.431,P=0.014],iFGF23水平在2组间无统计学差异[(1892.4±951.8)pg/ml比(1506.8±1094.9)pg/ml,Z=-1.151,P=0.258]。Logistic回归分析在校正了性别、年龄、透析龄、全段甲状旁腺激素(iPTH)、血钙和血磷水平后显示cFGF23水平与CAC的严重程度独立相关(OR:1.026,95%CI:1.003~1.048,P=0.024),iFGF23水平与CAC的严重程度无相关性(OR:0.999,95%CI:0.998~1.001,P=0.466)。共26例患者有完整的5年随访资料。CAC快速进展组和非快速进展组患者5年平均iPTH[506.7(166.8,567.5)pg/ml比684.6(349.7,1388.1)pg/ml,Z=-2.102,P=0.036],基线水平的CACs[45(0,142)分比317(174,964)分,Z=-2.943,P=0.003],随访终点时的cFGF23[954.7(891.3,1073.2)RU/ml比1128.6(1093.9,1252.8)RU/ml,Z=-3.192,P=0.001]、CACs[189(106,488)分比2228(1159,3104)分,Z=-3.971,P<0.001],△cFGF23[-55.4(-212.5,71.1)RU/ml比146.8(38.2,399.7)RU/ml,Z=-2.310,P=0.021]均有统计学差异。单因素相关分析结果提示患者△cFGF23与CAC进展呈正相关(r=0.399,P=0.043),CAC进展的速度与心血管事件的发生呈正相关(r=0.464,P=0.017)。结论高水平cFGF23或cFGF23快速上升可能反映MHD患者CAC的严重性或快速进展。在血液透析患者中,高水平的血清cFGF23水平与冠状动脉钙化的严重程度独立相关,△cFGF23与冠状动脉钙化进展速度呈正相关,血清iFGF23水平与冠状动脉钙化的严重程度及进展速度均无相关性。

Objective To investigate the correlation between the serum levels of C-terminal fibroblast growth factor 23(cFGF23)and intact fibroblast growth factor 23(iFGF23)and the severity and progression of coronary artery calcification(CAC)in patients on maintenance hemodialysis(MHD).Methods The MHD patients treated in Beijing Anzhen Hospital during the last 5 years were enrolled as the research subjects.Their baseline data and laboratory examination results were collected.Serum cFGF23 and iFGF23 were measured by ELISA.CAC score was estimated based on the CT scan image.Results A total of 37 patients were subjected to CAC examination.Patients in the severe CAC group had higher serum cFGF23 level than those in the non-severe CAC group[1128.6(1073.2,1252.8)RU/ml vs.1036.9(927.7,1121.8)RU/ml,Z=-2.431,P=0.014],while serum iFGF23 level had no statistical difference between the two groups of patients(1892.4±951.8 pg/ml vs.1506.8±1094.9 pg/ml,Z=-1.151,P=0.258).Logistic regression analysis revealed that serum cFGF23 level was independently correlated with the severity of CAC(OR=1.026,95%CI 1.003~1.048,P=0.024),while serum iFGF23 level had no correlation with the severity of CAC(OR=0.999,95%CI 0.998~1.001,P=0.466),after adjusting gender,age,dialysis vintage,iPTH,serum calcium and serum phosphorus of the patients.Twenty-six of the 37 patients completed the follow-up for 5 years.There were statistical differences in average iPTH within the 5 years[506.7(166.8,567.5)pg/ml vs.684.6(349.7,1388.1)pg/ml,Z=-2.102,P=0.036],baseline CAC scores[45(0,142)vs.317(174,964),Z=-2.943,P=0.003],serum cFGF23 at the end of follow-up[954.7(891.3,1073.2)RU/ml vs.1128.6(1093.9,1252.8)RU/ml,Z=-3.192,P=0.001],CAC score at the end of follow-up[189(106,488)vs.2228(1159,3104),Z=-3.971,P<0.001],and△cFGF23[-55.4(-212.5,71.1)RU/ml vs.146.8 RU/ml(38.2,399.7),Z=-2.31,P=0.021]between patients in rapid progress group and those in non-rapid progress group.Univariate correlation analysis found that△cFGF23 was positively correlated with CAC progression(r=0.399,P=0.043),and CAC progression rate was positively correlated with the occurrence of cardiovascular events(r=0.464,P=0.017).Conclusions Higher serum cFGF23 or rapid elevation of serum cFGF23 may indicate the MHD patient with severer or progressive CAC.In MHD patients,higher serum cFGF23 was independently correlated with the severity of CAC,△cFGF23 was positively correlated with the progression of CAC,while serum iFGF23 had no correlation with the severity and progression of CAC.