L-carnitine treatment in incident hemodialysis patients: the multicenter, randomized, double-blinded, placebo-controlled CARNIDIAL trial

Abstract

Background: L-carnitine levels decrease rapidly and steadily with duration of hemodialysis, and carnitine depletion can impair response to recombinant human erythropoietin (rHuEPO). The study hypothesis was that L-carnitine supplementation during the first year of hemodialysis would improve this response.

Design, setting, participants, & measurements: From October 2006 through March 2010, this multicenter, randomized, double-blinded study assigned 92 incident hemodialysis patients to receive placebo or 1 g of intravenous L-carnitine after each dialysis session for 1 year. The primary outcome measure compared the groups for rHuEPO resistance index (EPO-RI), defined as weekly rHuEPO doses (IU/kg body weight divided by hemoglobin level) (g/dl).

Results: In the L-carnitine group, carnitine concentration increased from a mean ± SD of 79 ± 51 µmol/L to 258 ± 137 µmol/L; in the placebo group, it declined from 68 ± 25 µmol/L to 53 ± 24 µmol/L (interaction group × time, P<0.001). Carnitine deficiency affected about 30% of the patients in the placebo group during the study period. EPO-RI varied from 15.8 ± 11.3 to 9.5 ± 5.8 IU/kg per g/dl in the placebo group and from 20.6 ± 12.8 to 15.6 ± 15.9 IU/kg per g/dl in the L-carnitine group, for a mean variation of -3.94 ± 12.5 IU/kg per g/dl and -2.98 ± 15.5 IU/kg per g/dl, respectively (P=0.7). After adjustment for baseline characteristics, the EPO-RI course was similar in each group (difference between groups, P=0.10; interaction group × time, P=0.9).

Conclusions: Carnitine levels decrease by about 11% ± 33% during the first year of hemodialysis. Treatment of incident hemodialysis patients with L-carnitine does not improve their response to rHuEPO.

Figure 1.

Flow chart. Distribution of patients from randomization to completion of the study period.

Figure 2.

Erythropoietin (EPO) resistance index in the placebo and the L-carnitine treatment groups. Error bars represent 95% confidence intervals. Calculated as mean weekly recombinant human erythropoietin doses (IU per kg body weight) divided by hemoglobin (g/dl) in the L-carnitine and the placebo groups.

Figure 3.

Carnitine values in the placebo and L-carnitine groups. (A) Total and free carnitine levels. (B) Free-to-total carnitine ratios. Error bars represent 95% confidence intervals.

Figure 4.

Lipid profiles in placebo and L-carnitine groups. Error bars represent 95% confidence intervals. (A) Total cholesterol. (B) HDL cholesterol. (C) LDL cholesterol. (D) Triglycerides.