慢性肾脏病3～5期患者肾功能与蛋白结合类毒素相关性研究  

Correlation between protein-bound uremic toxins and renal function in patients with chronic kidney disease stage 3- 5

作　　者：任真真[1] 伦立德[2] 李新伦[2] 李检[3] 窦桂芳[3] 

机构地区：[1]河北北方学院研究生院,河北张家口075000 [2]空军总医院肾病科,北京100142 [3]军事医学科学院药代动力学实验室,北京100091

出　　处：《军事医学》2015年第7期532-536,549,共6页Military Medical Sciences

摘　　要：目的测定慢性肾脏病（chronic kidney disease,CKD）3~5期（CKD3~5）患者血清马尿酸（hippuric acid,HA）、硫酸吲哚酚（indoxyl sulfate,IS）、硫酸对甲酚（p-cresyl sulfate,PCS）及3-羧基-4-甲基-5-丙基-2-呋喃丙酸（3-carboxy-4-methyl-5-propyl-2-furanpropionic acid,CMPF）4种蛋白结合类毒素的水平,分析肾功能与蛋白结合类毒素水平之间的关系。方法将112例CKD患者依据肾功能分为3组（CKD3~5）,另外选取60例健康志愿者作为对照组。应用HPLS-MS/MS检测技术测定各组血清中HA、IS、PCS、CMPF的浓度,并对估测肾小球滤过率（e GFR）与4种毒素浓度进行相关分析。结果与健康对照组相比,CKD3~5患者体内HA、IS、PCS及CMPF浓度均明显升高（P〈0.01）。各组CKD患者比较,HA、IS、PCS的水平随肾功能下降呈升高趋势（P〈0.01）,而CMPF血清浓度无显著变化（P〉0.05）。相关分析显示,e GFR与HA、IS、PCS及CMPF之间呈明显负相关。曲线回归分析显示,HA与e GFR之间曲线回归拟合方程式为Y=-46.171 ln X＋209.464（R2=0.601,P〈0.01）;IS与e GFR之间曲线回归拟合方程式为Y=-62.570 ln X＋279.537（R2=0.633,P〈0.01）;PCS与e GFR之间曲线回归拟合方程式为Y=-84.297 ln X＋383.172（R^2=0.529,P〈0.01）;CMPF与e GFR之间曲线回归拟合方程式为Y=-7.648 ln X＋53.546（R2=0.172,P〈0.01）。结论 CKD3~5患者体内HA、IS、PCS及CMPF水平均高于健康对照组,其中HA、IS、PCS的浓度随肾功能降低而逐渐升高,但CMPF浓度随肾功能进展变化不大。Objective To investigate the serum concentrations of protein-bound uremic toxins of hippuric acid（ HA）,indoxyl sulfate（ IS）,p-cresyl sulfate（ PCS） and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid（ CMPF） in patients with chronic kidney disease（ CKD） 3- 5 stages（ CKD3- 5） and to assess the correlation between renal function and protein-bound uremic toxin concentrations in CKD3- 5 patients. Methods Serum concentrations of HA,IS,PCS,and CMPF from 60 healthy volunteers and 112 CKD3- 5 patients were measured by liquid chromatography mass spectrometry / mass spectrometry（ HPLC-MS / MS）. Correlation analysis was conducted between the levels of HA,IS,PCS,CMPF and the estimated glomerular filtration rate（ e GFR）. Results Compared with healthy subjects,serum concentrations of these four solutes were significantly increased in CKD3- 5 patients（ all P〈0. 01）. The serum levels of HA,IS and PCS in CKD3-5 patients were significantly increased（ all P〈0. 05）,while those of CMPF did not significantly change（ P〈0. 05）. Linear correlation analysis showed that HA,IS,PCS and CMPF were in significantly negative correlation with e GFR. The curve regression analysis showed that the curvilinear regression fitting equation was Y =- 46. 171 ln X ＋ 209. 464（ R2= 0. 601,P〈0. 01） for HA and e GFR,Y =- 62. 570 ln X ＋ 279. 537（ R2= 0. 633,P〈0. 01） for IS and e GFR,Y =- 84. 297 ln X ＋383. 172（ R2= 0. 529,P〈0. 01） for PCS and e GFR,and was Y =- 7. 648 ln X ＋ 53. 546（ R2= 0. 172,P〈0. 01） for CMPF and e GFR. Conclusion The levels of the four types of protein-bound toxins in CKD3- 5 patients increase significantly compared to healthy subjects. The serum levels of HA,IS and PCS are increased when the renal function decreases,but the level of CMPF changes little. Renal dysfunction can lead to significantly elevated levels of HA,IS and PCS in CKD3- 5patients,but has little effect on CMPF.

关 键 词：慢性肾脏病 蛋白结合类毒素 肾小球滤过率 

分 类 号：R692[医药卫生—泌尿科学]