Anemia and carnitine supplementation in hemodialyzed patients

Carnitine supplementation in hemodialyzed patients was studied in a double- blinded, randomized, controlled trial in order to elucidate the effect of i ntravenous carnitine on renal anemia in patients treated with recombinant h uman erythropoietin (rHuEPO). Twenty stable hemodialysis (HD) patients received intravenous L-carnitine a fter 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. Afte r a run-in phase of six months with a stable rHuEPO requirement, the rHuEPO dose was adjusted monthly when necessary to maintain target hemoglobin lev els. At study entry (T0), plasma and red blood cell carnitine levels did no t 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 i ntravenous iron and L-carnitine (T4), the rHuEPO requirement decreased in 8 of 19 evaluable HD patients. In these responders, the weekly rHuEPO dose w as 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 increa sed comparably in both L-carnitine- and placebo-treated patients during fou r more months. According to our data, L-carnitine, in addition to iron supplementation, ma y have an effect on erythropoietin resistance and erythrocyte survival time in I-ID patients. More than half of our patients, however, showed no benef it. Further studies to identify those HD patients who might have a benefit of carnitine supplementation, as well as studies concerning the optimal dos age, duration, and way of administration of carnitine supplementation and i ts mechanism of action, are required.