Vanholder R
Department of Internal Medicine, University Hospital, Gent, Belgium.
Technol Health Care. 2000;8(6):373-9.
The uremic syndrome is the prototype of a slowly progressive endogenous intoxication, when a detoxifying organ (in this case the kidney) fails. It is characterized by the gradual retention of a host of metabolites, which is in part corrected by dialysis, allowing survival with an acceptable quality of life. This paper reviews the main problems of hemodialysis today, and possible solutions. Adequacy of dialysis is estimated currently from the concentration of urea, which is used as a marker molecule. The problem is that urea is not really toxic by itself. Other markers with known toxicity, such as middle molecules (300-12,000 D) and protein bound compounds should be considered. The question then arises whether the classical dialytic concept based on diffusion should be modified. Adsorptive systems may be strong binders of protein bound solutes. Other concepts that are now arising, and that may add to toxin removal, are slow and daily dialysis. Another question that could be raised is whether it would not be possible to support toxin removal, by administering peroral sorbants. Dialysis patients are prone to vascular disease and die early from cardio-vascular complications. One of the solutions for this problem could be to bring the blood of dialyzed patients into contact with antioxidants (e.g. vitamin C or E). The risk for perdialytic hemodynamic instability is increased in many dialysis patients. The ideal solution would be to develop an "intelligent" dialysis system, whereby blood volume and plasma osmolality are sensed continuously, and ultrafiltration and dialysate sodium concentration are adapted in function of this evolution. An adequate vascular access is indispensable to perform adequate dialysis, but thrombotic/stenotic complications are frequent. This could be prevented by molecular biological modification of vascular grafts, whereby genetic information is entered into the cells, blocking the natural chain of events that otherwise unavoidably leads to neointimal hyperplasia and atherosclerosis. Another old dream is to develop a wearable artificial kidney, whereby patients can move around, and be treated 24 hours per 24 hours, in stead of being treated intermittently at a specific location by the dialysis machine. According to some authors, part of the natural renal function could be replaced by cultured renal tubular cells, which are brought in contact with the blood of the patients. It is concluded that thrilling improvements lie ahead in the future, but the following questions arise: 1) What is the cost of all these improvements? 2) Will it remain possible to reimburse all this? 3) What is going to happen in transplantation, mainly regarding improvements in immunosuppression and the development of xenotransplantation?
尿毒症综合征是一种缓慢进展的内源性中毒的典型病症，此时解毒器官（在这种情况下是肾脏）功能衰竭。其特征是多种代谢产物逐渐潴留，部分可通过透析纠正，从而使患者能以可接受的生活质量存活。本文综述了当今血液透析的主要问题及可能的解决办法。目前透析充分性是根据尿素浓度来评估的，尿素被用作标记分子。问题在于尿素本身并非真正有毒。还应考虑其他已知有毒性的标记物，如中分子物质（300 - 12,000道尔顿）和蛋白结合化合物。于是就出现了一个问题，即基于扩散的传统透析概念是否应加以修正。吸附系统可能是蛋白结合溶质的强结合剂。目前正在兴起的、可能有助于毒素清除的其他概念是缓慢每日透析。另一个可能提出的问题是，通过口服吸附剂来辅助毒素清除是否可行。透析患者易患血管疾病，且常因心血管并发症过早死亡。解决这一问题的办法之一可能是使透析患者的血液与抗氧化剂（如维生素C或E）接触。许多透析患者透析期间血液动力学不稳定的风险增加。理想的解决办法是开发一种“智能”透析系统，能够持续感知血容量和血浆渗透压，并根据这些变化调整超滤和透析液钠浓度。充分的血管通路对于进行充分的透析必不可少，但血栓形成/狭窄并发症很常见。这可以通过对血管移植物进行分子生物学改造来预防，即将遗传信息导入细胞，阻断原本不可避免地导致内膜增生和动脉粥样硬化的自然事件链。另一个古老的梦想是开发一种可穿戴人工肾，使患者能够四处活动，并能随时接受治疗，而不是在特定地点由透析机进行间歇性治疗。据一些作者称，部分天然肾功能可由与患者血液接触的培养肾小管细胞替代。结论是未来将会有激动人心的改进，但随之而来的问题是：1）所有这些改进的成本是多少？2）是否仍有可能报销所有这些费用？
