Endogenous plasma carnitine pool composition and response to erythropoietin treatment in chronic haemodialysis patients.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Reuter
Stephanie E
SE
Sansom Institute, University of South Australia, Adelaide, SA, Australia.
Faull
Randall J
RJ
Ranieri
Enzo
E
Evans
Allan M
AM
D000328:Adult; D000368:Aged; D000740:Anemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D002331:Carnitine / Q000097:blood*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D006435:Renal Dialysis / Q000009:adverse effects
D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin; D002331:Carnitine