Principles of bound solute dialysis
Principles of bound solute dialysis
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DOI：
10.1111/j.1744-9987.2006.00352.x
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发表时间：
2006-04-01
影响因子：
1.9
通讯作者：
Patzer, J
中科院分区：
文献类型：
--
作者：
Patzer, J
与血液中的白蛋白结合并与进展性肝功能衰竭相关的毒素已被证明难以通过常规血液透析清除。然而，这种毒素可以通过向透析液中添加粘合剂来去除，该粘合剂用于在毒素穿过膜透析时捕获毒素。基于这一概念的几种方法正处于临床评价的不同阶段。这些方法共同的热力学基础已被用于开发“结合溶质透析”的工程描述，该描述已被进一步用于定义该方法的临床预期和局限性。该分析中出现了三个无量纲、独立可控的操作参数：（i）kappa，透析器传质/血液流速比（临床范围：0.5-2.5）;（ii）α，透析液/血液流速比（临床范围：0.1-2.0）;（iii）β，透析液/血液结合剂浓度比（临床范围：0.02-5.0）。在透析液中不存在结合剂的情况下，结合毒素的清除对κ和α敏感，更大的清除与更大的κ和/或α相关。然而，一旦向透析液中加入少量结合剂（β> 0.02），结合毒素的清除主要取决于κ，而与α和β无关。与传统血液透析相比，结合毒素去除的改善取决于毒素与白蛋白结合的紧密程度，范围从相对紧密结合的溶质（例如未结合的胆红素）增加6倍，到结合不太紧密的药物（例如华法林）增加1.5倍24小时灌注时间。在临床上，结合溶质透析可以在单程模式下进行，只需1-2 g白蛋白/L透析液。由于该过程的热力学性质所施加的限制，应尽可能早地在疾病进展时进行干预。
Toxins that bind to albumin in the bloodstream and are associated with progressing liver failure have proven refractory to removal by conventional hemodialysis. Such toxins can, however, be removed by adding a binder to the dialysate that serves to capture the toxin as it is dialyzed across the membrane. Several approaches based upon this concept are in various stages of clinical evaluation. The thermodynamic basis common to these approaches has been used to develop an engineering description of 'bound solute dialysis' which has further been used to define the clinical expectations and limitations of the approach. Three dimensionless, independently controllable, operating parameters emerged from this analysis (i): kappa, the dialyzer mass transfer/blood flow rate ratio (clinical range: 0.5-2.5); (ii) alpha, the dialysate/blood flow rate ratio (clinical range: 0.1-2.0); and (iii) beta, the dialysate/blood binder concentration ratio (clinical range: 0.02-5.0). In the absence of binder in the dialysate, bound toxin removal is sensitive to kappa and alpha, with greater removal associated with greater kappa and/or alpha. Bound toxin removal, however, is dependent primarily upon kappa and independent of alpha and beta once a small amount of binder, beta > 0.02, is added to the dialysate. The improvement in bound toxin removal over conventional hemodialysis is dependent upon how tightly the toxin binds albumin ranging from a 6-fold increase for a relatively tightly bound solute such as unconjugated bilirubin, to 1.5-fold increase for a less tightly bound drug such as warfarin at 24 h perfusion time. Clinically, bound solute dialysis can be practiced in single-pass mode with as little as 1-2 g albumin/L dialysate. Because of the constraints imposed by the thermodynamic nature of the process, intervention should be made as early in the disease progression as feasible.