Donnelly S M, Ali M A, Churchill D N
Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
Am J Kidney Dis. 1990 Nov;16(5):447-51. doi: 10.1016/s0272-6386(12)80057-6.
The dose of recombinant human erythropoietin (r-HuEPO) required to correct the anemia of end-stage renal disease (ESRD) varies among patients. The response to r-HuEPO is impaired if absolute or relative iron deficiency exists. Aluminum may cause a microcytic anemia in patients with ESRD, but the mechanism remains incompletely defined. Twenty-two patients in the Canadian Multicentre EPO trial were studied for 6 months. In this randomized double-blind placebo-controlled trial, free erythrocyte protoporphyrin (FEP) was used as an indicator of iron-deficient deficient erythropoiesis. The relationship of FEP to the estimates of iron availability (serum iron, transferrin saturation, ferritin) and iron utilization (corrected reticulocyte count, hemoglobin) was evaluated by multiple linear regression analysis. The effect of aluminum on FEP was evaluated by adjusting the statistical model for this variable. All patients were iron replete as assessed by serum ferritin. FEP was not related to serum aluminum before administration of r-HuEPO, but it was significantly correlated with aluminum in the treated group. In hemodialysis patients treated with r-HuEPO, the proportion of the variability explained by the parameters of iron utilization and iron availability was 0.27. The effect of aluminum increased this to 0.59. In hemodialysis patients not receiving r-HuEPO, the proportion of variability in FEP explained by the model increased from 0.16 to 0.28 by adjusting for aluminum. The data support the hypothesis that aluminum interferes with the bioavailability of stored iron for erythropoiesis and thus may result in a microcytic anemia in patients with ESRD or may blunt their response to r-HuEPO therapy.
纠正终末期肾病（ESRD）贫血所需的重组人促红细胞生成素（r-HuEPO）剂量因患者而异。如果存在绝对或相对铁缺乏，对r-HuEPO的反应会受损。铝可能导致ESRD患者出现小细胞性贫血，但其机制仍未完全明确。对加拿大多中心EPO试验中的22名患者进行了6个月的研究。在这项随机双盲安慰剂对照试验中，游离红细胞原卟啉（FEP）被用作缺铁性红细胞生成的指标。通过多元线性回归分析评估FEP与铁可用性估计值（血清铁、转铁蛋白饱和度、铁蛋白）和铁利用（校正网织红细胞计数、血红蛋白）之间的关系。通过针对该变量调整统计模型来评估铝对FEP的影响。根据血清铁蛋白评估，所有患者铁储备充足。在给予r-HuEPO之前，FEP与血清铝无关，但在治疗组中它与铝显著相关。在用r-HuEPO治疗的血液透析患者中，铁利用和铁可用性参数所解释的变异性比例为0.27。铝的影响将这一比例提高到了0.59。在未接受r-HuEPO的血液透析患者中，通过调整铝，模型所解释的FEP变异性比例从0.16增加到了0.28。这些数据支持以下假设：铝会干扰储存铁用于红细胞生成的生物利用度，因此可能导致ESRD患者出现小细胞性贫血，或削弱他们对r-HuEPO治疗的反应。
