Ifudu O, Feldman J, Friedman E A
Department of Medicine, State University of New York Health Science Center, Brooklyn 11203, USA.
N Engl J Med. 1996 Feb 15;334(7):420-5. doi: 10.1056/NEJM199602153340702.
Anemia (characterized by a hematocrit of 30 percent or lower) persists in 40 to 60 percent of patients treated for end-stage renal disease with maintenance hemodialysis, despite concomitant erythropoietin (epoetin) therapy. We tested the hypothesis that inadequate dialysis is a key reason for the insufficient response to erythropoietin in patients with end-stage renal disease who are receiving hemodialysis.
We prospectively studied 135 randomly selected patients undergoing hemodialysis who had been receiving intravenous erythropoietin for at least four months. The adequacy of dialysis was assessed by measuring the percent reduction in the blood urea nitrogen concentration and the serum albumin concentration. The hematocrit was measured weekly for four weeks, transferrin saturation was measured, and coexisting illnesses were documented. To determine the effect of an increased level of dialysis on the hematocrit, the thrice-weekly schedule of dialysis was increased to raise the mean urea-reduction value from 60.7 to 72 percent for six weeks in 20 consecutive patients whose base-line urea-reduction value was less than 65 percent. The change in the hematocrit in these patients was compared with that observed in the next 20 patients who had an equivalent base-line urea-reduction value but whose level of dialysis was not altered.
The mean hematocrit of the entire group was 29.2 +/- 4 percent, and the mean thrice-weekly dose of erythropoietin was 59 +/- 29 U per kilogram of body weight. The mean serum albumin concentration was 3.8 +/- 0.4 g per deciliter, the mean urea-reduction value was 62 +/- 4.8 percent, and the mean transferrin saturation was 20 +/- 9 percent. Multiple regression analysis revealed direct correlations between the hematocrit and the serum albumin concentration (P = 0.009) and between the hematocrit and the urea-reduction value (P = 0.012) after adjustment for other factors. A logistic-regression analysis indicated that an 11 percent increase in the urea-reduction value doubled the odds that a patient would have a hematocrit above 30 percent. After six weeks of increased intensity of dialysis in 20 patients with base-line urea-reduction values of less than 65 percent, the mean (+/- SE) hematocrit rose from 28.4 +/- 0.78 percent to 32.3 +/- 0.71 percent (P = 0.002); there was no significant change in a control group of 20 patients with equivalent base-line urea-reduction values in whom the dialysis level was not altered (28.2 +/- 0.84 percent to 26.3 +/- 0.85 percent; P = 0.175).
In patients with end-stage renal disease, inadequate hemodialysis is associated with a suboptimal response to erythropoietin therapy. Increasing the intensity of dialysis in patients with anemia who are receiving inadequate dialysis results in a significant increase in the hematocrit.
接受维持性血液透析治疗的终末期肾病患者中，40%至60%的患者尽管同时接受促红细胞生成素（依泊汀）治疗，但仍存在贫血（血细胞比容低于30%）。我们检验了这样一个假设，即透析不充分是接受血液透析的终末期肾病患者对促红细胞生成素反应不足的关键原因。
我们对135例随机选择的接受血液透析且已接受静脉注射促红细胞生成素至少四个月的患者进行了前瞻性研究。通过测量血尿素氮浓度和血清白蛋白浓度的降低百分比来评估透析充分性。连续四周每周测量血细胞比容，测量转铁蛋白饱和度，并记录并存疾病。为了确定增加透析水平对血细胞比容的影响，在20例基线尿素清除率低于65%的连续患者中，将每周三次的透析方案增加至六周，以使平均尿素清除率从60.7%提高到72%。将这些患者血细胞比容的变化与接下来20例具有相同基线尿素清除率但透析水平未改变的患者中观察到的变化进行比较。
整个组的平均血细胞比容为29.2±4%，每周三次的促红细胞生成素平均剂量为每公斤体重59±29单位。平均血清白蛋白浓度为3.8±0.4克/分升，平均尿素清除率为62±4.8%，平均转铁蛋白饱和度为20±9%。多元回归分析显示，在对其他因素进行调整后，血细胞比容与血清白蛋白浓度之间存在直接相关性（P = 0.009），血细胞比容与尿素清除率之间也存在直接相关性（P = 0.012）。逻辑回归分析表明尿素清除率增加11%会使患者血细胞比容高于30%的几率翻倍。在20例基线尿素清除率低于65%的患者中，强化透析六周后，平均（±标准误）血细胞比容从28.4±0.78%升至32.3±0.71%（P = 0.002）；在20例具有相同基线尿素清除率且透析水平未改变的对照组患者中无显著变化（从28.2±0.84%降至26.3±0.85%；P = 0.175）。
在终末期肾病患者中，血液透析不充分与促红细胞生成素治疗反应欠佳相关。对于透析不充分且贫血的患者，增加透析强度会使血细胞比容显著升高。
