Pickett J L, Theberge D C, Brown W S, Schweitzer S U, Nissenson A R
Department of Psychiatry and Biobehavioral Science, University of California at Los Angeles, Pasadena, CA, USA.
Am J Kidney Dis. 1999 Jun;33(6):1122-30. doi: 10.1016/S0272-6386(99)70150-2.
Recombinant human erythropoietin (rHuEPO) treatment has been shown to improve brain and cognitive function in anemic dialysis patients. Significant debate continues, however, regarding the appropriate target hematocrit (Hct) that will lead to the greatest benefits while considering possible side effects and costs of rHuEPO. Current practice results in an Hct averaging only 31% to 32% in dialysis patients, a level less than that achieved in the initial clinical trials and well less than normal. This study was designed to evaluate dialysis patients at the current practice Hct levels versus normal Hct levels (40% to 45%) to see if improvement in brain function resulted. Twenty patients with end-stage renal disease (ESRD) currently being treated with rHuEPO (mean Hct, 31.6%) were administered additional rHuEPO to reach normal Hct levels (mean, 42. 8%). Electroencephalogram (EEG) frequency analysis showed a significant decrease in EEG slowing at greater Hct values, and the auditory oddball and Continuous Performance Task tasks yielded significant electrode and time-by-electrode effects for P300 amplitude. Changes in P300 latency significantly correlated with increased Hct in the auditory oddball task. These findings suggest that further correction of anemia to normal Hct levels may result in continued improvement in neurocognitive function by improving the ability to sustain attention in easier tasks and by enhancing the ability to recognize, discriminate, and hold stimuli in memory for more difficult tasks.
重组人促红细胞生成素(rHuEPO)治疗已被证明可改善贫血透析患者的脑功能和认知功能。然而,关于合适的目标血细胞比容(Hct),即在考虑rHuEPO可能的副作用和成本的情况下能带来最大益处的目标血细胞比容,仍存在重大争议。目前的做法使得透析患者的Hct平均仅为31%至32%,这一水平低于最初临床试验所达到的水平,且远低于正常水平。本研究旨在评估处于当前实际Hct水平的透析患者与正常Hct水平(40%至45%)的透析患者,以观察脑功能是否得到改善。对20例目前正在接受rHuEPO治疗(平均Hct为31.6%)的终末期肾病(ESRD)患者额外给予rHuEPO,使其达到正常Hct水平(平均为42.8%)。脑电图(EEG)频率分析显示,在较高的Hct值时,EEG减慢显著减少,并且听觉oddball任务和连续操作任务在P300波幅方面产生了显著的电极和电极与时间交互作用。在听觉oddball任务中,P300潜伏期的变化与Hct升高显著相关。这些发现表明,将贫血进一步纠正至正常Hct水平可能通过提高在较简单任务中维持注意力的能力以及增强在较困难任务中识别、区分和在记忆中保留刺激的能力,从而持续改善神经认知功能。