低通量血液透析对蛋白结合类毒素清除效果的研究

The clearance of protein-bound uremic toxins in low-flux hemodialysis

目的探讨低通量血液透析(low-flux hemodialysis,LFHD)对维持性血液透析(maintenance hemodialysis,MHD)患者体内蛋白结合类毒素的清除效果。方法选择低通量血液透析治疗的MHD患者40例,采用高效液相色谱-串联质谱(high-performance liquid chromatography-tandem mass spectrometry,HPLC-MS/MS)法测定透析前、后血清中的马尿酸(hippuric acid,HA)、硫酸对甲酚(p-cresol sulphate,PCS)、硫酸吲哚酚(indoxyl sulphate,IS),3-羧基-4-甲基-5-丙基-2-呋喃丙酸(3-carboxy-4-methyl-5-propyl-2-furanpropionic acid,CMPF)的总体(Total,T)、游离(Free,F)浓度,计算其血清下降率和蛋白结合率。并测定透析废液中这4种蛋白结合类毒素的游离浓度,计算其溶质清除总量(total solute reduction,TSR)和透析溶质清除率(Kd),以观察低通量血液透析对蛋白结合类毒素的清除效果。结果透析后T-H A、T-PCS、T-IS及T-CMPF的血清下降率分别为(59.44±11.28)%、(32.36±9.28)%、(34.76±10.13)%和(5.60±15.98)%。透析废液中F-HA、F-PCS和F-IS的TSR分别为(112.88±31.72)mg、(31.55±9.85)mg和(35.40±10.38)mg;HA、PCS和IS的Kd分别为(41.25±5.09)ml/min、(8.09±3.58)ml/min、(9.89±2.76)ml/min。透析废液中CMPF极微量,基本测不出。结论低通量血液透析可以部分清除游离形式的蛋白结合类毒素;血清下降率并不足以评价低通量血液透析对蛋白结合类毒素的清除效果,蛋白结合类毒素在体内分布模型并非二室模型,可能为多室分布模型。

Objective To investigate the clearance of protein-bound uremic toxins in low-flux hemodialysis（LFHD） on maintenance hemodialysis（MHD） patients.Methods 40 patients with MHD from Air Force General Hospital were selected using high-performance liquid chromatography-tandem mass spectrometry（HPLC-MS/MS） method to determine the total and free serum concentration of hippuric acid（HA）,p-cresol sulphte（PCS）,indoxyl sulphate（IS）,3-carboxy-4-methyl-5-propyl-2-furanpropionic aeid（CMPF） before and after dialysis.And reduction rates of these solutes were calculated.Using a continuous part of dialysate method to collect the waste dialysate during dialysis,the concentration of HA,PCS,IS and CMPF in the dialy sate was and then the total solute reduction（TSR） and dialytic solute clearances（Kd） of these substances was calculated,to observe the effect on protein-bound toxins with low-flux hemodialysis.Results The total serum concentration of HA,PCS and IS declined,compared with predialysis;their reduction rates were（59.44± 11.28）%,（32.36± 9.28）%and（34.76± 10.13）%,respectively,while the reduction rate of CMPF was（5.60± 15.98）%.Elimination of protein-bound toxins assessed by their mass in dialysate was（112.88± 31.72） mg for HA,（31.55± 9.85）mg for PCS and（35.40± 10.38）mg for IS,respectively.And the Kd of HA,PCS and IS were（41.25± 5.09）ml/min,（8.09± 3.58）ml/min,（9.89± 2.76）ml/min,while CMPF could not be measured in dialysate.Conclusion Low-flux hemodialysis can partially clear protein-bound toxins,which were mainly the free part of these toxins.Reduction rate are not valid tools to estimate total solute removal of protein-bound uremic retention solutes.Protein-bound toxins in vivo distribution may not be the two compartment models,but the multi-compartmental distribution model.