Reuter Stephanie E, Faull Randall J, Ranieri Enzo, Evans Allan M
Sansom Institute, University of South Australia, Adelaide, SA, Australia.
Nephrol Dial Transplant. 2009 Mar;24(3):990-6. doi: 10.1093/ndt/gfn588. Epub 2008 Nov 5.
Anaemia is a common complication associated with haemodialysis and is usually managed by treatment with recombinant human erythropoietin (rHuEPO). However, many patients remain hyporesponsive to rHuEPO treatment despite adequate iron therapy. The effect of L-carnitine administration on rHuEPO dose and/or haematocrit in haemodialysis patients has been previously reported with equivocal results. This study examined the relationship between endogenous carnitine pool composition and rHuEPO requirements in long-term haemodialysis patients.
Pre-dialysis blood samples were collected from 87 patients and analysed for plasma L-carnitine and individual acylcarnitine levels by LCMS/MS. As an indication of rHuEPO responsiveness, erythropoietin resistance index (ERI) was calculated as rHuEPO dose/kg/week normalized for haemoglobin levels.
A significant negative correlation between L-carnitine levels and ERI was found (P = 0.0421). All patients categorized as high ERI (>0.02 microg/kg/week/gHb) exhibited subnormal L-carnitine levels (<30 microM); conversely, patients with normal L-carnitine levels (>30 microM) displayed low ERI values (<0.02 microg/kg/week/gHb). More importantly, the ratio of non-acetyl acylcarnitines/total carnitine was significantly positively correlated with ERI (P = 0.0062).
These data illustrate the relationship between carnitine levels and response to rHuEPO treatment in haemodialysis patients, in particular, the importance of the proportion of long-chain acylcarnitines within the plasma carnitine pool. This proportion may be more indicative of the response to L-carnitine supplementation than absolute L-carnitine levels alone.
贫血是血液透析常见的并发症,通常采用重组人促红细胞生成素(rHuEPO)治疗。然而,尽管进行了充分的铁剂治疗,许多患者对rHuEPO治疗仍反应低下。先前已有关于左旋肉碱给药对血液透析患者rHuEPO剂量和/或血细胞比容影响的报道,但结果不一。本研究探讨了长期血液透析患者内源性肉碱池组成与rHuEPO需求之间的关系。
采集87例患者透析前血样,采用液相色谱-串联质谱法(LCMS/MS)分析血浆左旋肉碱和各酰基肉碱水平。作为rHuEPO反应性的指标,计算促红细胞生成素抵抗指数(ERI),即根据血红蛋白水平标准化的rHuEPO剂量/千克/周。
发现左旋肉碱水平与ERI之间存在显著负相关(P = 0.0421)。所有ERI高(>0.02微克/千克/周/克血红蛋白)的患者左旋肉碱水平均低于正常(<30微摩尔/升);相反,左旋肉碱水平正常(>30微摩尔/升)的患者ERI值较低(<0.02微克/千克/周/克血红蛋白)。更重要的是,非乙酰酰基肉碱/总肉碱的比例与ERI显著正相关(P = 0.0062)。
这些数据阐明了血液透析患者肉碱水平与对rHuEPO治疗反应之间的关系,特别是血浆肉碱池中长链酰基肉碱比例的重要性。该比例可能比单纯的绝对左旋肉碱水平更能指示对左旋肉碱补充的反应。