陈钦开：血液净化技术在肾脏疾病治疗中的应用

血液净化技术在肾脏疾病治疗中的应用南昌大学第一附属医院肾内科陈钦开

提纲血液透析滤过(HDF, Online-HDF )高截止血液透析High Cut-Off Hemodialysis (HCO-HD)组合型人工肾(HD+HP)免疫吸附(immunoadsorption,IA)长时高频透析(每日夜间缓慢透析：NDHD )组合CRRT生物肾脏替代治疗(Renal bio-replacement therapy,RBT )

血液净化(blood

purification)

目的：清除体内的代谢废物或毒物，纠正水、电解质与酸碱的紊乱，维持机体内环境平衡，支持肾脏、心脏、肝脏、肺等维持生命的重要器官的功能。常用模式：HD PD HP HF CRRT PE

血液透析(HD)原理：◆利用弥散清除溶质◆利用超滤清除水分◆能够纠正电解质以及酸碱平衡的紊乱

血液灌流(hemoperfusion,HP)是将患者的血液引出体外，通过灌流器中吸附剂的吸附作用清除外源性和内源性毒物、药物以及代谢废产物，从而达到净化血液的目的。但是不能够清除体内多余的水份，不能够纠正电解质以及酸碱平衡紊乱，达到饱和后无效。传统主要用于药物以及毒物中毒抢救

血液滤过(hemofiltration, HF)模仿正常人肾小球滤过及肾小管重吸收原理，以对流的方式清除血液中的中小分子毒素及水分。基本技术与血液透析相似，所不同的是需要向血路管中补充大量置换液，其方式有二种，一种在滤器前输入，称为前稀释法，另一种在滤器后输入，称为后稀释法。

HF适应症血液滤过适用于急、慢性肾衰竭患者的治疗。下列情况时血液滤过优于血液透析。 1.顽固性高血压 2.低血压 3.心力衰竭与肺水肿 4.高脂血症 5.神经病变 6.高磷血 7.肝衰竭

从高通量透析到血液透析滤过

Adv Ren Repl Ther 1999; 6: 195-08

online HDF特殊要求 患者–应具有足够血流量的血管通路 透析器–具有高通量透析膜的透析器 透析机–RO反渗水装置/透析机可以产生无菌置换液 科室构建–科内定期有组织地评价置换液质量

HDF增加超滤量后溶质清除量变化

血流量 300 ml/min

Artif Organs 1998; 22: 20-5

CONTRAST:β2-微球蛋白变化40B - 2 - m ic r o g lo b u lin ( m g/L)

5.00

35 30

HD N=67 2M (mg/l) 12个月与治疗前的变化

P<0.020.00

-5.00

25 20

*

*

HDF * N=57*

*

-10.00

15Baseline 6 months 12 months

P<0.001

-15.00< 42 42-56> 56

ASN 2006, WCN 2007

对流量 (L/周, tertiles, N=19 per category)

on-line HDF治疗中血压稳定性改善高血压事件 (no./pat,month)3 21.1 HDF 1 HD HDF 2

1.9 1.1

1 0 0 3 6 9 12 15 18 time (months)全部患者均采用高通量聚砜膜透析器和高纯度透析用水 N= 15NDT 2001; 16: 1207-13

DOPPS:死亡率的风险

5– 14 liters

15– 25 liters

对年龄、性别、民族、国家、透析时间进

行了校正, 14致病条件,导管,体重, Kt/V n= 2165

Kidney Int 2006; 69:2087-2093

小HDF/ Online HDF:

结

可使某些被怀疑是尿毒症毒素的毒物被清除，而标准血液透析无法清除此类物质(如β2-微球蛋白)可使透析病人血液动力学稳定性和血压的控制更加容易可使透析病人死亡率发生显著降低，该作用可能与治疗剂量有关

高截止血液透析 High Cut-Off Hemodialysis(HCO-HD) 概念：血液滤过透析器滤过膜的有效孔径多为5060kDa,加强了透析治疗过程中的对流作用 分子截留量：反映膜孔径大小常规低通量1万Da高通量2万Da高截留量滤器5-6万Da

Beta2-microglobulin removal and plasma albumin levels with high cut-off hemodialysis. Backgrand:beta2-microglobulin (beta2MG) is pivotal to the pathogenesis of dialysisrelated amyloidosis. We compared the effects of high cut-off hemodialysis (HCO-HD) with those of standard high-flux hemodialysis (HF-HD) regarding the concentration and clearance of beta2MG and albumin. We enrolled ten patients with acute renal failure in a double-blind, cross-over, randomized controlled trial. Methods: Each patient received four hours of HCO-HD (estimated in vivo cutoff 5060 kDa) and four hours of HF-HD (estimated in vivo cutoff 15-20 kDa) in random order. Plasma and dialysate concentrations of beta2MG and albumin were measured at baseline and after four hours of each study treatment. Results: We found significantly greater diffusive beta2MG clearances for HCO-HD compared to HF-HD (at the start: 71.8 ml/min vs. 5.1 ml/min; P=0.008 and at the end: 68.8 ml/min vs. 5.7 ml/min; P=0.008). We found a reduction in plasma beta2MG concentrations of -31.6% during HCO-HD compared to an increase by 25.7% during HF-HD; P=0.008. At baseline (HCO-HD: 26.0 g/L vs. HF-HD: 26.5 g/L), and at the end of both treatments, plasma albumin concentrations were comparable (HCO-HD: 25.5 g/L vs. HF-HD: 26.5 g/L; P=0.25). During HCO-HD, albumin clearance was 1.9 ml/min at the start and decreased significantly to 0.8 ml/min at the end; P=0.008. HFHD had an albumin clearance of 0.01 ml/min. Conclusions: HCO-HD was more effective in decreasing plasma beta2MG concentrations than standard HF-HD and did not reduce plasma albumin levels. Further studies of HCO-HD in the treatment of dialysis-related beta2MG accumulation appear warranted.

Haase M et al. Int J Artif Organs. 2007 May;30(5):385-92

高截留量透析治疗：轻链水平的变化

治疗多发性骨髓瘤

轻链水平变化与肾功能恢复的关系治疗中血清轻链水平下降幅度与肾功能恢复直接相关