| Carnitine metabolism and the therapeutic use of carnitine has been a major area of interest in dialysis patients. The purpose of this study was to determine risk factors for suboptimal plasma carnitine concentrations and associated factors in hemodialysis patients and to determine if a defined group of chronic kidney disease (CKD), patients at increased risk for altered carnitine metabolism would respond to L-carnitine with regards to clinical parameters, perceived quality of life, and plasma acylcarnitine moieties. To examine these issues this study was done in two phases. Phase I was a cross sectional, observational study and phase II was a randomized, double-blind, clinical trial, both were conduct at a Midwest dialysis center on patients receiving hemodialysis (HD). Phase I resulted in subjects (n = 49) who were 60 +/- 16 (mean +/- SD) years of age and 48% male. 15% had type 1 Diabetes Mellitus (DM), 29% had type 2 DM, and 25% had left ventricular hypertrophy (LVH). The plasma free and total carnitine (FC and TC), acylcarnitine (AC), and acyl-to-free concentrations (A/F) were: 40.3 +/- 11.8mum/L, 22.8 +/- 7.3mum/L, 17.5 +/- 5.9mum/L, and 0.80 +/- 0.27, respectively. Blood urea nitrogen (BUN), parathyroid hormone (PTH), and ejection fraction were positively correlated and age and left atrial dilation were negatively correlated with TC. BUN and hematocrit were positively correlated and age was negatively correlated with FC. Subjects who used mannitol or were male had higher concentrations of both FC and TC, respectively. Patients in phase II met the following criteria: age >18 years, on HD 3x/wk >1 year, a plasma FC concentration of <40mumol/L and presence of 2 of the following risk factors: >65 yr, 2 yr duration of dialysis, female, use of aspirin and/or mannitol, have type 2 DM, left atrial dilation and/or LVH. In phase II, 50 patients were randomized into treatment and placebo groups. Patients were blindly treated with 2 g IV carnitine or placebo. The treatment period was for 24 weeks with data collected at 0, 12 and 24 weeks. Of the 50 recruited, 7 died, 7 withdrew, 2 had FC >40mumol/L, and 7 did not complete the final SF36 tool (available data used). Of the remaining 34 patients, the mean age was 68 +/- 14 yrs, 38% were female, 45% had diabetes. Mean Subjective Global Assessment, Body Mass Index, energy intake and protein intake were 6 +/- 0.8; 28 +/- 7; 17kcals/kg and 0.7g/kg respectively. Mean plasma TC, FC, Short Chain AC, Long Chain AC and A/F carnitine ratio were 36.05 + 10.64, 18.9 + 6.5, 11.12 + 4.01, 6.03 + 1.91 (mumol/L) and 0.97 + 0.34. Paired t-test analysis showed significant improvements in the treatment group for role-functioning (21.2 +/- 24.7 to 53.9 +/- 72), bodily pain (53.5 +/- 35.8 to 72.2 +/- 31.4), role-emotional (58.9 +/- 43.4 to 84.7 +/- 29.18), and the SF36 physical (36.1 +/- 9.6 to 39.7 +/- 8.5, p = 0.078) composite score; but no significant changes in the control group. Erythropoietin dose changes were significantly different between treatment and placebo groups from 0 to 24 weeks (1316 +/- 2795 versus 1464 +/- 2770 units). All acylcarnitine moieties were significantly increased at 12 and 24 weeks for patients in the treatment, but not control, group except for 2-methylbutynylcarnitine. |
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