Misra M, Nolph K D
Department of Internal Medicine, University of Missouri-Columbia 65212, USA.
Nefrologia. 2000;20 Suppl 3:25-32.
A vital conceptual difference between intermittent and continuous dialysis therapies is the difference in the relationship between Kt/V urea and dietary protein intake. For a given level of protein intake the intermittent therapies require a higher Kt/V urea due to the reasons mentioned above. The recently released adequacy guidelines by DOQI for intermittent and continuous therapies are based on these assumptions. The link between adequacy targets and patient survival is well documented for an intermittent therapy like HD. For a continuous therapy like CAPD however, the evidence linking improved peritoneal clearance to better survival is not as direct. However, present consensus allows one to extrapolate results based on HD. The concept of earlier and healthier initiation of dialysis is gaining hold and incremental dialysis forms an integral aspect of the whole concept. Tools like urea kinetic modeling give us valuable insight in making mathematical projections about the timing as well as dosing of dialysis. Daily home hemodialysis is still an underutilized modality despite offering best survival figures. Hopefully, with increasing availability of better and simpler machines its use will increase. Still several questions remain unanswered. Despite availability of data in hemodialysis patients suggesting that an increased dialysis prescription leads to a better survival, optimal dialysis dose is yet to be defined. Concerns regarding methodology of such studies and conclusions thereof has been raised. Other issues relating to design of the studies, variation in dialysis delivery, use of uncontrolled historical standards and lack of patient randomization etc also need to be considered when designing such trials. Hopefully an ongoing prospective randomized trial, namely the HEMO study, looking at two precisely defined and carefully maintained dialysis prescriptions will provide some insight into adequacy of dialysis dose and survival. In diabetic patients, the relationship between outcome and dialysis dose needs to be better defined. Data relating adequacy of dialysis to outcome in a pediatric population is not available. In dialysis therapy, the Risk/Dose (R/D) function does not bear a linear relationship. This together with a lack of proof equating peritoneal to renal clearance lends some uncertainty to the validity of the recommendation that there is a linear and constant decrease in RR for std (Kt/V) [equivalent standardized Kt/V calculated from average predialysis BUN for any frequency and/or combination of intermittent and continuous dialysis ref] up to 2.3 as reported in the CANUSA study. Due to the complex nature of this problem it may be prudent to undertake a multi-center trial with std (Kt/V) prospectively randomized to either 2.0 or 2.4. This would provide a reliable database to evaluate the R/D function over this critical range of normalized peritoneal urea clearance. Likewise in PD, the postulated linearity between dialysis dose and outcome needs to be studied in a prospective randomized manner. The amount of dialysis dose required for malnourished patients, diabetic and pediatric patients needs to be better defined. The role of aggressive dialysis in reversing malnutrition needs to be studied and studies need to be done to identify the most scientific use of V in malnourished patients. Justification of a healthy start/incremental dialysis based on outcome measures needs to be established and it's cost effectiveness validated by clinical trials. Again, a prospective randomized controlled trial comparing incremental dialysis with dietary protein restriction in patients with GFR < or = 10.5 ml/min/1.73 m2 with properly defined outcome measures like morbidity, mortality, decline of GFR and quality of life needs to be conducted. Comparisons of incremental hemodialysis and incremental peritoneal dialysis need to be made especially with regard to technique survival and preservation of residual renal function (RRF). (ABSTR
间歇性透析疗法与持续性透析疗法之间一个至关重要的概念性差异在于尿素清除率(Kt/V)与饮食蛋白质摄入量之间关系的不同。对于给定的蛋白质摄入量水平,由于上述原因,间歇性疗法需要更高的尿素清除率(Kt/V)。美国国家肾脏基金会透析充分性临床实践指南(DOQI)最近发布的关于间歇性和持续性疗法的充分性指南就是基于这些假设制定的。对于像血液透析(HD)这样的间歇性疗法,充分性目标与患者生存率之间的联系已有充分记录。然而,对于像持续性非卧床腹膜透析(CAPD)这样的持续性疗法,将改善的腹膜清除率与更好的生存率联系起来的证据并不那么直接。不过,目前的共识允许人们根据血液透析的结果进行推断。更早且更健康地开始透析的概念正在逐渐确立,递增式透析是整个概念的一个重要组成部分。像尿素动力学建模这样的工具能让我们在对透析时机和剂量进行数学预测方面获得有价值的见解。尽管每日家庭血液透析提供了最佳的生存数据,但它仍然是一种未得到充分利用的治疗方式。有望随着更好、更简单的机器越来越容易获得,其使用将会增加。不过,仍有几个问题尚未得到解答。尽管血液透析患者的数据表明增加透析处方能带来更好的生存率,但最佳透析剂量尚未确定。人们对这类研究的方法及其结论提出了担忧。在设计此类试验时,还需要考虑与研究设计、透析实施的差异、使用未加控制的历史标准以及缺乏患者随机分组等相关的其他问题。有望正在进行的一项前瞻性随机试验,即血液透析(HEMO)研究,观察两种精确界定且精心维持的透析处方,将能为透析剂量的充分性和生存率提供一些见解。在糖尿病患者中,结局与透析剂量之间的关系需要更明确地界定。关于儿科人群中透析充分性与结局的数据尚不可得。在透析治疗中,风险/剂量(R/D)函数并不呈线性关系。再加上缺乏将腹膜清除率等同于肾脏清除率的证据,使得如下建议的有效性存在一些不确定性:即如加拿大/美国(CANUSA)研究中所报告的,对于标准的(Kt/V)[根据任何频率和/或间歇性与持续性透析组合的透析前平均血尿素氮(BUN)计算得出的等效标准化Kt/V],当达到2.3时,相对风险(RR)会呈线性且持续下降。由于这个问题的复杂性,可能谨慎的做法是进行一项多中心试验,将标准的(Kt/V)前瞻性随机分为2.0或2.4。这将提供一个可靠的数据库,以评估在这个关键的标准化腹膜尿素清除率范围内的R/D函数。同样,在腹膜透析中,透析剂量与结局之间假定的线性关系需要以前瞻性随机的方式进行研究。营养不良患者、糖尿病患者和儿科患者所需的透析剂量需要更明确地界定。积极透析在逆转营养不良方面的作用需要研究,并且需要开展研究以确定在营养不良患者中最科学地使用V的方法。需要基于结局指标确立健康起始/递增式透析的合理性,并通过临床试验验证其成本效益。同样,需要进行一项前瞻性随机对照试验,比较GFR≤10.5 ml/min/1.73 m²的患者中递增式透析与饮食蛋白质限制,要有适当界定的结局指标,如发病率、死亡率、GFR下降情况和生活质量。需要对递增式血液透析和递增式腹膜透析进行比较,尤其是在技术生存率和残余肾功能(RRF)的保留方面。(摘要)