Kletzmayr J, Mayer G, Legenstein E, Heinz-Peer G, Leitha T, Hörl W H, Kovarik J
Department of Medicine, University of Vienna, Austria.
Kidney Int Suppl. 1999 Mar;69:S93-106.
Carnitine supplementation in hemodialyzed patients was studied in a double-blinded, randomized, controlled trial in order to elucidate the effect of intravenous carnitine on renal anemia in patients treated with recombinant human erythropoietin (rHuEPO). Twenty stable hemodialysis (HD) patients received intravenous L-carnitine after each dialysis session in a dosage of 5 (N = 15) and 25 (N = 5) mg/kg, respectively, together with intravenous iron saccharate (20 mg/HD session) for four months and without iron for a further four months. Twenty patients received placebo instead of carnitine with an identical iron regimen. After a run-in phase of six months with a stable rHuEPO requirement, the rHuEPO dose was adjusted monthly when necessary to maintain target hemoglobin levels. At study entry (T0), plasma and red blood cell carnitine levels did not correlate significantly with the rHuEPO requirement. However, plasma free and total carnitine levels showed a significant negative correlation with erythrocyte survival time at T0. After four months of coadministration of intravenous iron and L-carnitine (T4), the rHuEPO requirement decreased in 8 of 19 evaluable HD patients. In these responders, the weekly rHuEPO dose was decreased significantly by 36.9+/-23.3% (183.7+/-131.7 at T0 vs. 126.6+/-127.9 U/kg/week at T4, P < 0.001). The rHuEPO requirement, however, was unchanged when all carnitine-treated patients were compared between T0 and T4 (T0: 172.0+/-118.0 vs. T4: 152.3+/-118.8 U/kg/week, P = 0.07, NS), but the erythropoietin resistance index decreased significantly in this group (T0: 16.0+/-11.0 vs. T4: 13.6+/-10.5 U/kg/week/g of hemoglobin, P < 0.02). The erythrocyte survival time was measured in five HD patients treated with iron and carnitine at T0 and T4. Two out of these patients were carnitine responders and showed an increase of erythrocyte survival time of 15 and 20%, respectively. After the withdrawal of iron supplementation, the rHuEPO requirement increased comparably in both L-carnitine- and placebo-treated patients during four more months. According to our data, L-carnitine, in addition to iron supplementation, may have an effect on erythropoietin resistance and erythrocyte survival time in HD patients. More than half of our patients, however, showed no benefit. Further studies to identify those HD patients who might have a benefit of carnitine supplementation, as well as studies concerning the optimal dosage, duration, and way of administration of carnitine supplementation and its mechanism of action, are required.
为阐明静脉注射肉碱对接受重组人促红细胞生成素（rHuEPO）治疗的患者肾性贫血的影响，在一项双盲、随机、对照试验中对血液透析患者补充肉碱进行了研究。20例稳定的血液透析（HD）患者在每次透析后分别接受剂量为5（N = 15）和25（N = 5）mg/kg的静脉注射L-肉碱，同时静脉注射蔗糖铁（每次透析20 mg），持续四个月，之后四个月不补充铁。20例患者接受安慰剂而非肉碱，铁剂治疗方案相同。在有稳定的rHuEPO需求的六个月导入期后，必要时每月调整rHuEPO剂量以维持目标血红蛋白水平。在研究开始时（T0），血浆和红细胞肉碱水平与rHuEPO需求无显著相关性。然而，T0时血浆游离和总肉碱水平与红细胞存活时间呈显著负相关。在静脉注射铁和L-肉碱联合给药四个月后（T4），19例可评估的HD患者中有8例rHuEPO需求降低。在这些反应者中，每周rHuEPO剂量显著降低36.9±23.3%（T0时为183.7±131.7 U/kg/周，T4时为126.6±127.9 U/kg/周，P < 0.001）。然而，当比较所有接受肉碱治疗的患者在T0和T4时的情况时，rHuEPO需求没有变化（T0：172.0±118.0 vs. T4：152.3±118.8 U/kg/周，P = 0.07，无显著性差异），但该组中促红细胞生成素抵抗指数显著降低（T0：16.0±11.0 vs. T4：13.6±10.5 U/kg/周/g血红蛋白，P < 0.02）。在T0和T4时对5例接受铁和肉碱治疗的HD患者测量了红细胞存活时间。其中2例患者对肉碱有反应，红细胞存活时间分别增加了15%和20%。在停止补充铁后四个月，接受L-肉碱和安慰剂治疗的患者rHuEPO需求均有类似增加。根据我们的数据，除补充铁外，L-肉碱可能对HD患者的促红细胞生成素抵抗和红细胞存活时间有影响。然而，超过一半的患者未显示出益处。需要进一步研究以确定哪些HD患者可能从补充肉碱中获益，以及关于补充肉碱的最佳剂量、持续时间、给药方式及其作用机制的研究。
