Clinical Investigation

Kidney International (1990) 38, 904–911; doi:10.1038/ki.1990.289

Multicenter trial of L-carnitine in maintenance hemodialysis patients. I. Carnitine concentrations and lipid effects

Thomas A Golper, Marsha Wolfson, Suhail Ahmad, Raimund Hirschberg, Paul Kurtin, Lois Anne Katz, Robert Nicora, Don Ashbrook and Joel D Kopple

Oregon Health Sciences University & Portland VA Medical Center, Portland, Oregon; Scribner Kidney Center, School of Medicine, University of Washington, Seattle, Washington; Harbor-UCLA Medical Center and UCLA Schools of Medicine and Public Health, Los Angeles, California; Bellevue Hospital Medical Center, New York, New York; Current address: New England Medical Center, Boston, Massachusetts; New York VA Medical Center and NYU School of Medicine, New York, New York; and Kendall McGaw Laboratories, Inc., Irvine, California, USA

Correspondence: Thomas A Golper MD, Kidney Disease Program, University of Louisville, 500 South Floyd Street, Louisville, Kentucky 40292, USA.

Received 17 March 1989; Revised 10 April 1990; Accepted 31 May 1990.

Top

Abstract

Multicenter trial of L-carnitine in maintenance hemodialysis patients. I. Carnitine concentrations and lipid effects. Previous studies have reported conflicting results of carnitine supplementation on plasma lipids in patients with chronic renal failure. We therefore performed a four center, double-blind placebo controlled trial to evaluate the effects of post-hemodialysis intravenous injection of L-carnitine in ESRD patients on maintenance hemodialysis. Thirty-eight patients received up to six months of L-carnitine infusions (20 mg/kg) post-dialysis and 44 patients received placebo infusions. In both groups of patients, baseline pre-dialysis plasma and red blood cell total carnitine levels were normal, but pre-dialysis plasma-free carnitine concentrations and free/ total ratios were subnormal, and plasma acyl levels were elevated. Post-dialysis plasma free and total carnitine concentrations were also subnormal. Plasma and red blood cell total carnitine levels rose eightfold in carnitine recipients, but were unchanged from baseline in those receiving placebo. There were no significant changes observed in plasma triglycerides, HDL-cholesterol or other lipoprotein parameters in either the carnitine or placebo treated groups. We conclude that carnitine metabolism is altered in uremia. Furthermore, in a randomly-selected hemodialysis population, L-carnitine injection at the dose of 20 mg/kg results in significant increases in blood (and perhaps tissue) carnitine levels, but this is not associated with any major effects on lipid profiles.

Top

References

  1. Goa KL, Brogden RN: L-carnitine. A preliminary review of its pharmacokinetics, and its therapeutic use in ischaemic cardiac disease and primary and secondary carnitine deficiencies in relationship to its role in fatty acid metabolism. Drugs 34:1–24, 1987
  2. Bohmer T, Bergrem H, Eiklid K: Carnitine deficiency induced during intermittent haemodialysis for renal failure. Lancet 1:126–128, 1978 | PubMed | ChemPort |
  3. Bartel LL, Hussey JL, Shrago E: Perturbation of serum carnitine levels in human adults by chronic renal disease and dialysis therapy. Am J Clin Nutr 34:1314–1320, 1981 | PubMed | ChemPort |
  4. Gusmano R, Oleggini R, Perfumo F: Plasma carnitine concentration and dyslipidemia in children on maintenance hemodialysis. J Pediatr 99:429–432, 1981
  5. Leschke M, Rumpf KW, Eisenhauer T, Fuchs C, Becker K, Kothe U, Scheler F: Quantitative assessment of carnitine loss during hemodialysis and hemofiltration. Kidney Int 24(Suppl 16):S143–S146, 1983
  6. Moorthy AV, Rosenblum M, Rajaram R, Shug AL: A comparison of plasma and muscle carnitine levels in patients on peritoneal or hemodialysis for chronic renal failure. Am J Nephrol 3:205–208, 1983 | PubMed | ChemPort |
  7. Panzetta G, Bonadonna G, Giovene P, DeGrandis D: Carnitine kinetics during dialysis: Evidence of unilateral transport from tissues to plasma. Nephron 41:230–234, 1985 | PubMed | ChemPort |
  8. Bagdade JD, Albers JJ: Plasma high-density lipoprotein concentrations in chronic-hemodialysis and renal transplant patients. N Engl J Med 296:1436–1439, 1977 | PubMed | ISI | ChemPort |
  9. Frank WM, Rao TKS, Manis T, Delano BG, Avram MM, Saxena AK, Carter AC, Friedman EA: Relationship of plasma lipids to renal function and length of time on maintenance hemodialysis. Am J Clin Nutr 31:1886–1892, 1978
  10. Gutman RA, Uy A, Shalhoub RJ, Wade AD, O'Connell JMB, Recont L: Hypertriglyceridemia in chronic non-nephrotic renal failure. Am J Clin Nutr 26:165–172, 1973
  11. Ibels LS, Simons LA, King JO, Williams PF, Neale FC, Stewart JH: Studies on the nature and causes of hyperlipidemia in uraemia, maintenance dialysis, and renal transplantation. Quart J Med 44:601–614, 1975
  12. Ponticelli C, Barbi G, Cantaluppi A, Donati C, Annoni G, Brancaccio D: Lipid abnormalities in maintenance dialysis patients and renal transplant recipients. Kidney Int 13(Suppl 8):S72–S78, 1978
  13. Bertoli M, Battistella PA, Vergani L, Naso A, Gasparotto ML, Romagnoli GF, Angelini C: Carnitine deficiency induced during hemodialysis and hyperlipidemia: Effect of replacement therapy. Am J Clin Nutr 34:1496–1500, 1981 | PubMed | ChemPort |
  14. Maebashi M, Imamura A, Yoshinaga K, Sato T, Funyu T, Ishidoya Y, Hirayama N: Carnitine depletions as a probable cause of hyperlipidimia in uremic patients on maintenance hemodialysis. Tohoku J Exp Med 139:33–42, 1983
  15. Chan MK, Persaud JW, Varghese Z, Baillod RA, Moorhead JF: Response patterns to DL-carnitine in patients on maintenance haemodialysis. Nephron 30:240–243, 1982
  16. Guarnieri GF, Ranieri F, Toigo G, Vasile A, Ciman M, Rizzoli V, Moracchiello M, Campanacci L: Lipid-lowering effect of carnitine in chronically uremic patients treated with maintenance hemodialysis. Am J Clin Nutr 33:1489–1492, 1980
  17. Bougneres PF, Lacour B, Di Giulio S, Assan R: Hypolipaemic effect of carnitine in uraemic patients. Lancet 1:1401–1402, 1979
  18. Lacour B, Di Giulio S, Chanard J, Ciancioni C, Haguet M, Lebkiri B, Basile C, Drüeke T, Assan R, Funk-Brentano JL: Carnitine improves lipid anomalies in haemodialysis patients. Lancet 2:763–765, 1980
  19. Albertazzi A, Capelli P, Di Paolo B, Pola P, Tondi P, Vaccario O: Endocrine-metabolic effects of L-carnitine in patients on regular dialysis treatment. Proc Eur Dial Transplant Assoc 19:302–307, 1982
  20. Vacha GM, Giorcelli G, Siliprandi N, Corsi M: Favorable effects of L-carnitine treatment on hypertriglyceridemia in hemodialysis patients: Decisive role of low levels of high-density lipoprotein-cholesterol. Am J Clin Nutr 38:532–540, 1983
  21. Caruso U, Cravotto E, Tisone G, Elli M, Stortoni F, D'Iddio S, Pola P, Savi L, Tondi P, Casciani CU: Long-term treatment with L-carnitine in uremic patients undergoing hemodialysis: Effects on the lipid pattern. Curr Ther Res 33:1098–1103, 1983
  22. Casciani CV, Caruso U, Cravotto E, D'Iddio S, Corsi M, et al: L-carnitine in haemodialysis patients. Arzneimittel-Forshung 32:293–297, 1982
  23. Suzuki Y, Narita M, Yamazaki N: Effects of L-carnitine on arrhythmias during hemodialysis. Jpn Heart J 23:349–359, 1982
  24. Bellinghieri G, Savica V, Mallamace A, Di Stefano C, Consolo F, Spagnoli LG, Villaschi S, Palmieri G, Corsi M, Maccari F: Correlation between increased serum and tissue L-carnitine levels and improved muscle symptoms in hemodialyzed patients. Am J Clin Nutr 38:523–531, 1983 | PubMed |
  25. Yderstraede KB, Pederson FB, Dragsholt C, Trostman A, Laier E, Larsen HF: The effect of L-carnitine on lipid metabolism in patients on chronic haemodialysis. Nephrol Dial Transplant 1:238–241, 1987
  26. Nilsson-Ehle P, Cederblad G, Fagher B, Monti M, Thysell H: Plasma lipoproteins, liver function and glucose metabolism in haemodialysis patients: Lack of effect of L-carnitine supplementation. Scand J Clin Lab Invest 45:179–184, 1985
  27. Aubia J, Masramon J, Lloveras J, Llorach M, Andolz P: Carnitine in haemodialysis patients. (letter) Lancet 2:1028–1029, 1980
  28. Weschler A, Aviram M, Levin M, Better OS, Brook JG: High dose of L-carnitine increases platelet aggregation and plasma triglyceride levels in uremic patients on hemodialysis. Nephron 38:120–124, 1984
  29. Wanner C, Förstner-Wanner S, Schaeffer G, Schollmeyer P, Hörl WH: Serum-free carnitine, carnitine esters and lipids in patients on peritoneal and hemodialysis. Am J Nephrol 6:206–211, 1986 | PubMed |
  30. Golper TA: Therapy for uremic hyperlipidemia. Nephron 38:217–225, 1985
  31. Cederblad G, Lindstedt S: A method for the determination of carnitine in the picomole range. Clinica Chem Acta 37:235–243, 1972
  32. Warnick GR, Benderson J, Albers JJ: Dextran sulfate-magnesium precipitation procedure for quantitation of high density lipoprotein cholesterol, in Selected Methods in Clinical Chemistry, edited by Cooper GR, Washington
  33. Hainline A, Karon J, Lippel K, editors: Manual of Laboratory Operations. Lipid and Lipoprotein Analysis. U.S. Department of Health and Human Services, Publice Health Service, NIH, 1982
  34. Albers JJ, Wahl PW, Cabana VG, Hazzard WR, Hoover JJ: Quantitation of apolipoprotein A-1 of human plasma high density lipoprotein. Metab 25:633, 1976
  35. Albers JJ, Cabana VG, Hazzard WR: Immunoassay of human plasma apolipoprotein B. Metab 24:1339, 1975
  36. Warnick GR: Enzymatic methods for quantification of lipoprotein lipids, in Methods in Enzymology, Orlando, edited by Albers JJ, Segrest JP, Academic Press Inc., 1986, Vol. 129:101–123
  37. Warnick GR: Precipitation methods for quantification of lipids, in: Ibid, 1986, edited by Bachorik PS, Albers JJ, Vol. 129:78–100
  38. BMDP Statistical Software. Dixon WJ, chief editor, Berkeley, University of California Press, 1985
  39. Borum PR, Meguid MM, Jeffers S, Terg JJ, Bennett SG, York CM: Plasma carnitine and erythrocyte carnitine as indicators of carnitine status in TPN patients. (abstract) Am J Clin Nutr 37:705, 1983
  40. Borum PR: Regulation of tissue carnitine concentrations. 1st International McGaw Carnitine Symposium, Athens, June 25–26, 1984
  41. Katrib K, Louni AH, Ferard G: Carnitine in human polymorphonucleocytes, mononuclear cells, and platelets. Ibid 46:734–35, 1987
  42. Guarnieri G, Toigo G, Situlin R, Faccini L, et al: Muscle biopsy in chronically uremic patients: Evidence for malnutrition. Kidney Int 24(Suppl 16):S187–S193, 1983
  43. Bazzi C, DiDonato S, Castiglione A, Corsi M, D'Amico G: Carnitine metabolism in short and long term maintenance hemodialysis, in Clinical Aspects of Human Carnitine Deficiency, edited by Borum PR, New York, Pergamon Press, 1986, p. 245
  44. Wanner C, Försstner-Wanner S, Rössle C, Fürst P, Schoolmeyer P, Hörl WH: Carnitine metabolism in patients with chronic renal failure: Effect of L-carnitine supplementation. Kidney Int 32(Suppl 22):S132–S135, 1987
  45. Bohles H, Lehnert W: The effects of intravenous L-carnitine on propionic acid excretion in acute propionic acidaemia. (abstract) Eur J Pediatr 143:61, 1984
  46. Wanner C, Hörl WH: Carnitine abnormalities in patients with renal insufficiency: Pathophysiological and therapeutical aspects. Nephron 50:89–102, 1988 | PubMed | ISI | ChemPort |
  47. Ahmad S, Robertson T, Golper TA, et al: Multicenter study of L-carnitine injection in patients on maintenance hemodialysis. II. Biochemical and Exercise effects. (This issue)
  48. Vacha GM, Giorcelli G, D'Iddio S, Corsi M: Effects of long-term treatment with L-carnitine on the lipid pattern of patients undergoing haemodialysis. Proc Eur Dial Transpl Assoc 22:121–126, 1985
  49. Zilleruelo G, Novak M, Hsia SL, et al: Effect of dialysate composition on the lipid response to L-carnitine supplementation. Kidney Int 36(Suppl 27):S259–S263, 1989
  50. Wanner C, Hörl WH: Potential role of carnitine in patients with renal insufficiency. Klin Wochenschr 64:579–586, 1986
  51. Wanner C, Wieland H, Wackerle B, et al: Ketogenic and antiketogenic effects of L-carnitine in hemodialysis patients. Kidney Int 36(Suppl 27):S264–S268, 1989

Extra navigation

.
ADVERTISEMENT