慢性肾病患者血清Klotho,HE4,UMOD表达水平与疾病预后的相关性研究

Study on the Relationship between the Expression Level of Klotho,HE4 and Uromodulin and the Development of Chronic Kidney Disease

目的研究慢性肾病(chronic kidney disease,CKD)患者血清Klotho,人附睾蛋白4(HE4)和尿调节素(UMOD)表达水平在评估疾病预后中的参考价值。方法对120例CKD患者及100例健康体检对照者血清同时应用ELISA检测Klotho和HE4,电化学发光法检测UMOD表达水平,分析各因子与肾小球滤过率(GFR)之间的关系。患者随访12个月后,根据GFR下降幅度分为恶化组和稳定组,比较两组之间血清因子变化差异,采用Kaplan-Meier生存曲线分析血清因子与预后的关系。结果CKD患者血清Klotho,UMOD,GFR和HE4表达水平与健康对照组相比,差异均有统计学意义(t=22.492,58.235,23.668和33.341,均P<0.05)。Klotho,UMOD与GFR呈现正相关性(r=0.682,0.582,P<0.001),HE4与GFR呈负相关性(r=-0.627,P<0.001)。随访结束时血清Klotho,UMOD水平明显低于随访前,HE4水平明显高于随访前,恶性组患者的变化幅度与稳定组相比差异有统计学意义(t=13.263,18.600和16.645,均P<0.0015)。随访12个月后患者死亡45例(37.50%),高Klotho,UMOD水平组不良预后风险低于低Klotho,UMOD水平组,高HE4水平组不良预后风险高于低HE4水平组,差异均有统计学意义(χ^(2)=4.511,3.960,7.484;P=0.034,0.047,0.006)。结论慢性肾病患者血清中Klotho,HE4,UMOD均存在异常表达,其中血清Klotho,UMOD水平降低以及HE4水平升高可增加肾功能恶化风险,三种血清因子联合可提高对预后评估的参考价值。

Objective To study the significance of Klotho,HE4 and UMOD expression in patients with chronic kidney disease(CKD)in evaluating the prognosis of CKD.Methods the expression levels of Klotho and HE4 in peripheral blood of 120 CKD patients and 100 healthy patients were detected by ELISA,and the expression level of UMOD by electrochemiluminescence method.The relationship between various factors and glomerular filtration rate(GFR)were analysed.At the end of 12 months follow-up,according to the decrease of GFR,the patients were divided into deterioration group and stable group.The differences of serum factors between the two groups were compared,Kaplan-Meier survival curve was used to analyze the relationship between serum factors and prognosis.Results The expression levels of Klotho,UMOD,GFR and HE4 in CKD patients were significantly higher than those in healthy controls(t=22.492,58.235,23.668 and 33.341,all P<0.05).Klotho and UMOD showed positive correlation with GFR(r=0.682,0.582,P<0.001),the correlation coefficient was 0.682,0.582,and the HE4 has a negative correlation with the GFR(r=-0.627,P<0.001).At the end of the follow-up,the level of serum Klotho,UMOD was significantly lower than that before the follow-up,and the level of HE4 was significantly higher than that before the followup.There was a significant difference between the malignant group and the stable group(t=13.263,18.600 and 16.645,all P<0.0015).45 patients(37.50%)died after 12 months follow-up.The risk of adverse renal prognosis in high Klotho and UMOD group was lower than that in low Klotho and UMOD group,and the risk of adverse renal prognosis in high HE4 group was higher than that in low HE4 group(χ^(2)=4.511,3.960,7.484;P=0.034,0.047,0.006).Conclusion Klotho,HE4 and UMOD are all abnormal expression in the serum of patients with chronic nephropathy,in which the decrease of serum Klotho and UMOD level and the increase of HE4 level can increase the risk of renal function deterioration,and three serum factors can improve the reference value for prognosis evaluation.