Caramelo C, Soto C, Neira F, López M D, Jiménez S, Albalate M, de Oña R, Llamas P, Deudero J J P
Servicio de Hematología, Clínica de la Concepción, Universidad Autónoma de Madrid, Av. Reyes Católicos, 2 28040 Madrid.
Nefrologia. 2004;24(4):351-6.
The sudden interruption of recombinant human erythropoietin (rHuEPO) in end-stage renal disease (ESRD) patients leads to rapid anemization. The mechanisms of this phenomenon are, however, insufficiently understood. The present study examined the response to immediate rHuEPO withdrawal in dialysis patients.
10 chronic hemodialysis (HD) patients regularly receiving rHuEPO were studied. rHuEPO was stopped and reinitiated after 7 days. Reticulocyte profile, haemoglobin and haematocrit were measured at 0, 7 and 15 days. As a complementary study, and with the purpose of analyzying whether uremia was a relevant factor, 10 non-uremic male Wistar rats were treated with rHuEPO. After two weeks, rHuEPO was withdrawn in 5 animals, and continued for 7 additional days in the remainder. The same variables than in the human study were determined.
Changes in reticulocyte subtypes from baseline to day 7 were: total 18.2 +/- 0.9 vs 14.3 +/- 1.8% (p < 0.06); high-fluorescence (HFR): 2.6 +/- 0.4 vs 0.75 +/- 0.2 (p < 0.001); medium-fluorescence (MFR): 13.0 +/- 1.1 vs 6.6 +/- 0.9% (p < 0.02); and low-fluorescence (LFR): 84.2 +/- 1.4 vs 92.7 +/- 1% (p NS). The baseline pattern was recovered upon 7 days of rHuEPO reinitiation (p NS). Mean hemoglobin and hematocrit decreased by day 14 (p < 0.02) in spite of rHuEPO reinitiation at day 7. In non-uremic rats, changes were similar to that in the ESRD patients.
rHuEPO induces changes in the reticulocyte pattern, consisting in a reduction of immature reticulocytes. These changes appear to be independent of the presence of uremia. Accordingly, complete rHuEPO withdrawal in HD patients will cause a rapidly-developing anaemia due to an alteration in the reticulocyte maturation series; therefore, sudden rHuEPO interruption should be avoided whenever is possible. As a collateral application, the specific changes described herein have potential use for detecting illegal administration of rHuEPO.
终末期肾病（ESRD）患者重组人促红细胞生成素（rHuEPO）的突然中断会导致迅速贫血。然而，这种现象的机制尚未完全了解。本研究检测了透析患者对立即停用rHuEPO的反应。
研究了10名定期接受rHuEPO治疗的慢性血液透析（HD）患者。停用rHuEPO 7天后重新开始使用。在第0、7和15天测量网织红细胞谱、血红蛋白和血细胞比容。作为补充研究，为了分析尿毒症是否是一个相关因素，对10只非尿毒症雄性Wistar大鼠进行rHuEPO治疗。两周后，5只动物停用rHuEPO，其余动物继续使用7天。测定与人体研究相同的变量。
从基线到第7天，网织红细胞亚型的变化为：总数18.2±0.9%对14.3±1.8%（p<0.06）；高荧光（HFR）：2.6±0.4%对0.75±0.2%（p<0.001）；中荧光（MFR）：13.0±1.1%对6.6±0.9%（p<0.02）；低荧光（LFR）：84.2±1.4%对92.7±1%（p无统计学意义）。重新开始使用rHuEPO 7天后恢复到基线模式（p无统计学意义）。尽管在第7天重新开始使用rHuEPO，但到第14天平均血红蛋白和血细胞比容仍下降（p<0.02）。在非尿毒症大鼠中，变化与ESRD患者相似。
rHuEPO诱导网织红细胞模式发生变化，表现为未成熟网织红细胞减少。这些变化似乎与尿毒症的存在无关。因此，HD患者完全停用rHuEPO会因网织红细胞成熟系列改变而导致迅速发展的贫血；因此，应尽可能避免突然停用rHuEPO。作为附带应用，本文所述的特定变化在检测rHuEPO非法使用方面具有潜在用途。
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