慢性肾脏病患者血清Klotho蛋白水平与血管钙化的相关性研究

Study on correlation between serum Klotho protein level with vascular calcification in patients with chronic kidney disease

目的探讨慢性肾脏病(CKD)患者血清Klotho蛋白水平与血管钙化的相关性。方法选取2014年1-12月在该院肾内科住院的CKD患者107例,另外选取年龄、性别匹配的20例健康体检者为对照组。采用ELISA法测定血清Klotho蛋白水平,采用腹部侧位X线片评估患者的腹主动脉钙化(AAC),同时采用彩色多普勒超声检测患者肱动脉依赖性血管舒张功能(FMD)和颈动脉中膜厚度(cIMT)。比较CKD患者与健康人群血清Klotho蛋白水平的差别;探讨血清Klotho蛋白水平与慢性肾脏病-矿物质和骨异常(CKD-MBD)、血管功能紊乱如血管钙化、内皮功能紊乱、cIMT的相关性并分析其临床意义。结果 CKD组患者血清Klotho蛋白水平和FMD显著低于对照组,而cIMT和AAC评分显著高于对照组。随着CKD进展,血清Klotho蛋白水平也显著降低。CKD患者血清Klotho蛋白水平与年龄(r=-0.348,P<0.01)、甲状旁腺激素(iPTH)的对数(log iPTH,r=-0.366,P<0.01)、cIMT(r=-0.192,P<0.05)及AAC评分(r=-0.251,P<0.01)呈负相关,与肾小球滤过率(eGFR,r=0.387,P<0.01)、1,25-二羟维生素D3(1,25-(OH)2-D3,r=0.311,P<0.01)及FMD(r=0.190,P=0.048)呈正相关。FMD≥6.0%、cIMT<1.0mm及AAC评分等于0分的患者血清Klotho蛋白水平均显著高于FMD<6.0%、cIMT≥1.0mm及AAC评分大于0分的患者。多因素Logistic回归分析显示年龄(OR=3.63,95%CI:1.75~8.89,P=0.002)、平均动脉压(MBP)(OR=2.98,95%CI:1.45~7.69,P=0.09)、蛋白尿(OR=1.97,95%CI:1.16~3.73,P=0.022)、血清Klotho蛋白水平(OR=0.60,95%CI:0.39~0.98,P=0.007)是血管钙化的独立预测因子。结论随着CKD进展,血清Klotho蛋白水平显著降低;血清Klotho蛋白水平下降是血管钙化的独立预测因子。

Objective To investigate the correlation between serum Klotho protein level with vascular calcification in the patients with chronic kidney disease（CKD）.Methods One hundred and seven inpatients with CKD in the nephrology department of the hospital from January 2014 to December 2014 were selected and 20 age-and sex-matched persons undergoing healthy physical examination served as the control group.Serum Klotho ptotein level was measured by ELISA.Abdominal aortic calcification（AAC）was assessed by abdominal lateral X-rays.Meanwhile the brachial arterial flow-mediated dilatation（FMD）and carotid intima-media thickness（cIMT）were determined by the color Doppler ultrasound.The difference of serum Klotho protein levels were compared between the CKD patients and healthy people.The relationship between the serum Klotho protein level with CKD-mineral and bone disorder（CKD-MBD）and vascular dysfunction such as vascular calcification,.endothelial dysfunction and cIMT was investigated and its clinical significance was analyzed.Results Serum Klotho protein level and FMD in the CKD group were significantly lower than those in the control group,while the cIMT and AAC scores were significantly higher than those in the control group.Serum Klotho level was significantly decreased along with the progression of CKD.Serum Klotho protein level were negatively correlated with the age（r=-0.348,P0.01）,log iPTH（r=-0.366,P0.01）,cIMT（r=-0.192,P0.05）and AAC score（r=-0.251,P0.01）,and positively correlated with eGFR（r=0.387,P0.01）,1,25-dihydroxyvitamin D3 level（r=0.311,P0.01）and FMD（r=0.190,P0.05）in the CKD patients.The Klotho protein level in the patients with FMD≥6.0,cIMT1.0 mm and AAC score=0 were significantly higher than those in the patients with FMD6.0,cIMT≥1.0 mm and AAC score0.The multivariate Logistic regression analysis showed that age（OR=3.63,95%CI：1.75-8.89,P=0.002）,MBP（OR=2.98,95%CI：1.45-7.69,P=0.009）,albuminuria（OR=1.97,95%CI：1.16-3.73,P=0.022）,serum Klotho protein level（OR=0.60,95%CI：0.39-0.98,P=0.007）were the independent predictive factors of vascular calcification.Conclusion Serum Klotho protein level in the CKD patients is significantly decreased along with CKD progression;serum Klotho protein level decrease is an independent predictive factor of vascular calcification.