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• Hemodialysis-Leg Cramps: The role of L-Carnitine Supplementation
  Anil K Saxena
  Published on: 23 June 2003

• Published on: 23 June 2003

  Hemodialysis-Leg Cramps: The role of L-Carnitine Supplementation

  • Anil K Saxena, Consultant Renal Physician, Division of Nephrology, Post-graduate department of Medicine,
  • Other Contributors:
    • Wahid Uzzaman

  Dear Editor

  Painful muscle cramps occuring in long-term hemodialysis (HD) patients most often involve the lower extremities typically the gastrocnemius and the small muscles of foot and interefere with free and effective voluntry activity. They represent an extremely common and annoying problem associated with HD treatment. The HD associated muscle cramps have been estimated to occur in about 20% of the HD sessions....

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  Dear Editor

  Painful muscle cramps occuring in long-term hemodialysis (HD) patients most often involve the lower extremities typically the gastrocnemius and the small muscles of foot and interefere with free and effective voluntry activity. They represent an extremely common and annoying problem associated with HD treatment. The HD associated muscle cramps have been estimated to occur in about 20% of the HD sessions.[1] Benna et al in their study of 14000 HD treatments reported a cumulative incidence of cramps of 86%, on 103 patients of chronic renal failure.[2]

  Muscle cramps have been found to be frequently associated with ultrafiltration of large volumes of fluids resulting into a state of relative hypovolumia due to the discrepancy between the rate of ultrafiltration and vascular refilling during HD.The observations that hypotension may herald or accompany muscle cramps and that the muscle cramps can be relieved by isotonic volume expansion with saline or albumin solutions- support the role of plasma volume depletion.[3] Progressive hypoosmolality during HD increases the passive transport of water intracellularly, further contracting the plasma volume beyond the reduction cause by ultrafiltration. Hypotonicity enhances the tension and the mechanical activity in an isolated muscle and thus may precipitate muscle cramps by the reduction in myoadenylate deaminase levels intracellularly.[4] Postdialytic alkalimia has been associated with a reduction in red blood cell levels of 2,3 di-phosphoglycerate. This alteration in acid-base status could produce tissue hypoxia resulting in muscle cramps.[1]

  In addition, patients undergoing HD treatment have been reported to have a secondary form of carnitine deficiency. Several factors such as significant dialytic losses, decreased endogenous production and the undernutrition due to dietary restriction lead to the secondary form of carnitine deficiency among long-term HD patients.[5] Carnitine is a naturally occuring aminoacid that is also synthesized mainly in the liver, brain and kidneys while meat and dairy products are rich dietary sources. Carnitine facilitates the entry of fatty acids into the mitochondria for the production of energy (ATPs).[6] During the last decade, there had been a greater interest in the treatment of dialysis-leg cramps through L- carnitine supplementation. A reduction in the intradialytic muscle cramps and asthenia in patients recieving L- carnitine, has been reported by several researchers [7-10]. Variable supplemental doses (5-100 mg/kg) of L-carnitine have been administered either intravenously-at the end of each dialysis session, orally- just prior to HD session or via addition to the dialyzate. Bellingheri et al in their double blind cross-over trial evaluating the the effect of 60 days of L-carnitine oral therapy (2 g/day) on a group of 14 uremic patients on intermittent HD- reported the simultaneous increase in the levels of metabolite in the blood and the muscles with the significant reductions in the incidence of asthenis and muscle cramps in the treatment group.[10]

  Likewise, in a double blind placebo controlled randomized multicenter clinical trial conducted by Ahmad et al. on 82 long-term HD patients who were given either carnitine (n=38) or placebo (n=44)- intra dialytic hypotension, asthenia, excercise tolerance and muscle cramps were found to be significantly reduced in carnitine treated group.[8]However, the optimal dose, duration of treatment and the best route of administration is not yet known; the cost of treatment as well, is a limiting factor for the routine L-carnitine supplementation in the patients having dialysis leg cramps. Nonetheless the most economical and practical way suggested is, possibly either the oral ingerstion of 660-990 mg/day or 2-3 grams just prior to the begining of the hemodialysis session.[11]

  References

  (1) Hakim RM, Lazarus JM. Complications during Hemodialysis. In: Clinical Dialysis, AR Nissensen, RN Fine, DE Gentle ( eds,). Norwalk, CT : Appleton–Centry-Crofts, 1984, pp 192-195.

  (2) Benna P, Lacquaniti, Triolo G, Farrero P, Berghamasco B. Acute neurologic complications of hemodialysis. Ital J Neurol Sci 1981; 2: 53- 57.

  (3) Blagg CR. Acute complications associated with hemodialysis. In : Replacement of Renal Function by Dialysis, JF Maher (Ed.)Dordrecht, The Neatherlands: Kluwer Academic Publishers, 1989, pp 762-763.

  (4) Adams RD, Victor M. Principles of Neurology. Mc-Graw-Hill Information Services Co, 1989.

  (5) Rodriguez-Segade S, Alonso de la Pena C, Paz JM, et al. Carnitine deficiency in hemodialyzed patients. Clin Chim Acta 1986, 159: 249-256.

  (6) Bahl JJ, Bressler R. The pharmacology of carnitine. Am Rev Pharmcol Toxicol 1987;27: 257-277.

  (7) Golper TA, Ahmad S. L-Carnitine administration to hemodialysis patients: Has its time come? Semin Dial 1992;5: 94-98.

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  Conflict of Interest:
  None declared.

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