The pathophysiology of leg cramping during dialysis and the use of carnitine in its treatment.

Leg cramping is a common side effect of hemodialysis, and this is frequently treated by the administration of carnitine, but this is not effective in every patient. Alkalosis is a key component of the etiology of leg cramping during hemodialysis sessions. This is mediated through the binding of calcium ions to serum albumin, which causes hypocalcemia, and an increase in the release of calcium ions from the sarcoplasmic reticulum. Normally the calcium pump on the sarcoplasmic reticulum consumes ATP and quickly reuptakes the released calcium ions, which rapidly stops excessive muscle contractions. Thus, carnitine deficiency results in prolonged muscle contraction because of ATP depletion. However, during ATP production, carnitine is only involved up to the stage of acyl-CoA transport into mitochondria, and for the efficient generation of ATP, the subsequent metabolism of acyl-CoA is also important. For example, β-oxidation and the tricarboxylic acid cycle may be affected by a deficiency of water-soluble vitamins and the electron transport chain requires coenzyme Q10, but statins inhibit its production. The resulting accumulation of excess long-chain acyl-CoA in mitochondria inhibits enzymes involved in energy production. Thus, carnitine administration may be used more effectively if clinicians are aware of its specific physiologic roles.