Altered carnitine metabolism in dialysis patients with reduced physical function may be due to dysfunctional fatty acid oxidation

• Published in: Nephrology, dialysis, transplantation Vol. 27; no. 1; pp. 304 - 310
• Main Authors: AUSTIN MURPHY, William Jared, STEIBER, Alison, CONNERY, Grissim Clark, CARDER, Jackie, SPRY, Leslie, HOPPEL, Charles
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 2012
• Subjects: Activities of Daily Living; Aged; Anemia - drug therapy; Anemia - etiology; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Carnitine - analogs & derivatives; Carnitine - blood; Carnitine - metabolism; Cross-Sectional Studies; Emergency and intensive care: renal failure. Dialysis management; Erythrocytes - pathology; Erythropoietin - therapeutic use; Fatty Acids - metabolism; Female; Follow-Up Studies; Glomerulonephritis; Humans; Intensive care medicine; Lipid Metabolism; Male; Medical sciences; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Oxidation-Reduction; Prognosis; Quality of Life; Renal Dialysis - adverse effects; Kidney disease; Human; Urinary system disease; Hemodialysis; acylcarnitine; Inflammation; Metabolism; Carnitine; Extrarenal dialysis; Aminoacid; Renal failure; Dialysis; Oxidation; physical function; fatty acid oxidation
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfr334

It has been reported that hemodialysis patients have elevated plasma acylcarnitine concentrations, which correlates to reduced red blood cell integrity. It has also been reported that the supplementation of L-carnitine for these patients improves anemia, glucose metabolism and muscle function, but the mechanism of these relationships remains unknown. We hypothesized that the cause of increased plasma acylcarnitines is incomplete fatty acid oxidation and the underlying disturbance of metabolism reduces muscle function, resulting in decreased ability to function and quality of life, and glucose availability, resulting in decreased red blood cell integrity and worsened anemia. This analysis was conducted on baseline data from a clinical trial of carnitine supplementation in hemodialysis patients with reduced physical function and free carnitine levels. Partial correlations controlling for age, gender, hemoglobin and subjective global assessment score for each acylcarnitine species and outcome were computed using SPSS version 17.0 and a significance level of P < 0.05. To measure the impact of acylcarnitine acyl chain length on these relationships, the correlation coefficients were categorized by chain length and linear regressions were computed for each outcome measure. Linear regression analysis (n = 58) revealed significant negative relationships between chain length and Short Form-36 physical composite score, sit-to-stand count and 6-min walk distance (r(2) = 0.635, 0.332 and 0.347, respectively) and a significant positive relationship with erythropoietin dose (r(2) = 0.181). Our data revealed that longer acyl chain length significantly predicts poorer physical function and worsened anemia, and this data supports our proposed mechanism, which may lead to increased understanding of altered carnitine metabolism in hemodialysis patients.