Tomson C R, Edmunds M E, Chambers K, Bricknell S, Feehally J, Walls J
Department of Nephrology, Leicester General Hospital, UK.
Nephrol Dial Transplant. 1992;7(8):817-21.
The development of end-stage renal disease (ESRD) in patients with sickle-cell anaemia results in increased transfusion dependence, increasing the risk of iron overload. Correction of anaemia with recombinant human erythropoietin (rHuEpo) in dialysis patients might also result in stimulation of haemoglobin F production, which protects against sickling, although very high doses were required to achieve this effect in non-uraemic animals. rHuEpo was administered to three transfusion-dependent patients with ESRD and homozygous sickle-cell disease (initial dose 100 U/kg twice weekly, increasing to 125 U/kg at 6 weeks, and to 150 U/kg at 9 weeks in two patients). This resulted in reticulocytosis and increased circulating erythroid blast-forming units. Total haemoglobin was predominantly HbA (i.e. transfused blood) at the start of the study, reflecting transfusion dependence, but after 3 months' treatment was between 60 and 94% HbS. No sickling crises occurred. Haemoglobin F remained at less than 3% of total haemoglobin. One patient was withdrawn at 10 weeks with CAPD peritonitis. The other two patients completed 12 weeks' treatment without transfusion but final Hb concentrations were 4.5 and 5.5 g/dl. Whether larger doses of rHuEpo will be more successful in managing such patients remains unclear. No effect on HbF production can be expected.
镰状细胞贫血患者终末期肾病的发展导致输血依赖性增加，从而增加了铁过载的风险。在透析患者中用重组人促红细胞生成素（rHuEpo）纠正贫血也可能会刺激血红蛋白F的产生，而血红蛋白F可防止红细胞镰变，尽管在非尿毒症动物中需要非常高的剂量才能达到这种效果。对三名依赖输血的终末期肾病和纯合子镰状细胞病患者给予rHuEpo（初始剂量为每周两次，每次100 U/kg，6周时增至125 U/kg，两名患者在9周时增至150 U/kg）。这导致了网织红细胞增多和循环中红系爆式集落形成单位增加。在研究开始时，总血红蛋白主要是HbA（即输血的血液），这反映了输血依赖性，但经过3个月的治疗后，HbS占60%至94%。未发生镰变危象。血红蛋白F仍占总血红蛋白的不到3%。一名患者在10周时因持续性非卧床腹膜透析（CAPD）腹膜炎退出研究。另外两名患者在未输血的情况下完成了12周的治疗，但最终血红蛋白浓度分别为4.5 g/dl和5.5 g/dl。更大剂量的rHuEpo在治疗此类患者时是否会更成功仍不清楚。预计对血红蛋白F的产生没有影响。
