Clark W R, Leypoldt J K, Henderson L W, Mueller B A, Scott M K, Vonesh E F
Renal Division, Baxter Healthcare Corporation, McGaw Park, Illinois 60085, USA.
J Am Soc Nephrol. 1999 Mar;10(3):601-9. doi: 10.1681/ASN.V103601.
One potential benefit of chronic hemodialysis (HD) regimens of longer duration or greater frequency than typical three-times-weekly schedules is enhanced solute removal over a relatively wide molecular weight spectrum of uremic toxins. This study assesses the effect of variations in HD frequency (F: per week), duration (T: min per treatment), and blood/dialysate flow rates (QB/QD: ml/min) on steady-state concentration profiles of five surrogates: urea (U), creatinine (Cr), vancomycin (V), inulin (I), and beta2-microglobulin (beta2M). The regimens assessed for an anephric 70-kg patient were: A (standard): F = 3, T = 240, QB = 350, QD = 600; B (daily/short-time): F = 7, T = 100, QB = 350, QD = 600; C/D/E (low-flow/long-time): F = 3/5/7, T = 480, QB = 300, QD = 100. HD was simulated with a variable-volume double-pool model, which was solved by numerical integration (Runge-Kutta method). Endogenous generation rates (G) for U, Cr, and beta2M were 6.25, 1.0, and 0.17 mg/min, respectively; constant infusion rates for V and I of 0.2 and 0.3 mg/min, respectively, were used to simulate middle molecule (MM) G values. Intercompartment clearances of 600, 275, 125, 90, and 40 ml/min were used for U, Cr, V, I, and beta2M, respectively, For each solute/regimen combination, the equivalent renal clearance (EKR: ml/min) was calculated as a dimensionless value normalized to the regimen A EKR, which was 13.4, 10.8, 6.6, 3.7, and 4.8 ml/min for U, Cr, V, I, and beta2M, respectively. For regimens B, C, D, and E, respectively, these normalized EKR values were U: 1.04, 0.96, 1.58, and 2.22; Cr: 1.03, 1.08, 1.80, and 2.55; V: 1.06, 1.32, 2.21, and 3.12; I: 1.05, 1.54, 2.57, and 3.62; beta2M: 1.00, 1.27, 1.73, and 2.19. The extent of post-HD rebound (%) was highest for regimens A and B, ranging from 16% (urea) to 50% (inulin), and lowest for regimen E, ranging from 6% (urea) to 28% (beta2M). The following conclusions can be made: (1) Relative to a standard three-times-weekly HD regimen of approximately the same total (weekly) treatment duration, a daily/short-time regimen results in modest (3 to 6%) increases in effective small solute and MM removal. (2) Relative to a standard three-times-weekly HD regimen, a three-times-weekly low-flow/long-time regimen results in comparable effective small solute removal and progressive increases in MM and beta2M removal. A daily low-flow/long-time regimen substantially increases the effective removal of all solutes.
与典型的每周三次透析方案相比，采用更长疗程或更高频率的慢性血液透析（HD）方案的一个潜在益处是，在相对较宽的尿毒症毒素分子量范围内，溶质清除得到增强。本研究评估了HD频率（F：每周次数）、疗程（T：每次治疗分钟数）以及血液/透析液流速（QB/QD：毫升/分钟）的变化对五种替代物（尿素（U）、肌酐（Cr）、万古霉素（V）、菊粉（I）和β2微球蛋白（β2M））稳态浓度分布的影响。针对一名70千克无肾患者评估的方案如下：A（标准方案）：F = 3，T = 240，QB = 350，QD = 600；B（每日/短疗程）：F = 7，T = 100，QB = 350，QD = 600；C/D/E（低流量/长疗程）：F = 3/5/7，T = 480，QB = 300，QD = 100。采用可变容积双池模型模拟HD过程，通过数值积分（龙格 - 库塔法）求解。U、Cr和β2M的内源性生成速率（G）分别为6.25、1.0和0.17毫克/分钟；分别采用0.2毫克/分钟和0.3毫克/分钟的V和I恒定输注速率来模拟中分子（MM）的G值。U、Cr、V、I和β2M的跨室清除率分别为600、275、125、90和40毫升/分钟。对于每种溶质/方案组合，等效肾清除率（EKR：毫升/分钟）计算为相对于方案A的EKR的无量纲值，方案A中U、Cr、V、I和β2M的EKR分别为13.4、10.8、6.6、3.7和4.8毫升/分钟。对于方案B、C、D和E，这些归一化的EKR值分别为：U：1.04、0.96、1.58和2.22；Cr：1.03、1.08、1.80和2.55；V：1.06、1.32、2.21和3.12；I：1.05、1.54、2.57和3.62；β2M：1.00、1.27、1.73和2.19。HD后反弹程度（%）在方案A和B中最高，范围为16%（尿素）至50%（菊粉），在方案E中最低，范围为6%（尿素）至28%（β2M）。可得出以下结论：（1）相对于总（每周）治疗时长大致相同的标准每周三次HD方案，每日/短疗程方案可使有效小分子溶质和MM清除率适度提高（3%至6%）。（2）相对于标准每周三次HD方案，每周三次的低流量/长疗程方案可实现相当的有效小分子溶质清除，并使MM和β2M清除率逐步提高。每日低流量/长疗程方案可大幅提高所有溶质的有效清除率。
