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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(R2=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 determine the levels of serum hippuric acid (HA), indoxyl sulfate (IS), p-cresol sulfate (p-cresol) in patients with chronic kidney disease (CKD) 4-methyl-5-propyl-2-furanpropionic acid (CMPF) Toxin levels and to analyze the relationship between renal function and protein-bound toxoid levels. Methods One hundred and twelve patients with CKD were divided into 3 groups according to renal function (CKD3 ~ 5), and another 60 healthy volunteers were selected as control group. The serum concentrations of HA, IS, PCS and CMPF in each group were determined by HPLS-MS / MS. Correlation analysis was performed between the estimated glomerular filtration rate (e GFR) and the concentration of four toxins. Results Compared with healthy controls, the concentrations of HA, IS, PCS and CMPF in patients with CKD3 ~ 5 were significantly increased (P <0.01). The levels of HA, IS and PCS increased with the decline of renal function (P <0.01) in all the CKD patients, but there was no significant change in CMPF serum concentration (P> 0.05). Correlation analysis showed a significant negative correlation between e GFR and HA, IS, PCS and CMPF. Curve regression analysis showed that the fitting equation of curve regression between HA and e GFR was Y = -46.171 ln X + 209.464 (R2 = 0.601, P <0.01). The curve regression fitting equation between IS and e GFR was Y = - 62.570 ln X + 279.537 (R2 = 0.633, P <0.01). The curve fitting regression equation between PCS and e GFR was Y = -84.297 ln X + 383.172 (R2 = 0.529, P <0.01) The fitting equation for the inter-curve regression was Y = -7.648 ln X + 53.546 (R2 = 0.172, P <0.01). Conclusions The levels of HA, IS, PCS and CMPF in patients with CKD3 ~ 5 are higher than those in healthy controls. The concentrations of HA, IS and PCS gradually increase with the decrease of renal function, but the changes of CMPF with little change of renal function.