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Patients on hemodialysis (HD) have impaired exercise performance. Carnitine homeostasis is also abnormal in this population. As carnitine is an important cofactor for muscle energy metabolism, exercise performance and skeletal muscle carnitine metabolism were characterized in eight HD patients, and in five age-matched controls. Each patient underwent graded bicycle exercise testing to define maximal performance, and prolonged exercise at 70% of their peak work capacity. Muscle (vastus lateralis) total carnitine content (carnitine plus all acylcarnitines) at rest was lower in HD patients than in controls (2320 +/- 1190 vs. 3800 +/- 940 nmol/g, P less than 0.05). In patients on HD, muscle carnitine content was inversely correlated to time on HD (r = -0.74, P less than 0.05), and positively correlated to peak exercise performance (r = 0.77, P less than 0.05). In patients on HD, 8 +/- 7% of the muscle carnitine pool at rest was short-chain acylcarnitines (similar to the distribution in controls), but 32 +/- 5% of the plasma carnitine pool consisted of short-chain acylcarnitines. With high-intensity exercise in patients on HD, muscle short-chain acylcarnitine content increased from 130 +/- 130 to 1380 +/- 820 nmol/g (P less than 0.01). The change in muscle short-chain acylcarnitine content with exercise was correlated with the increase in muscle lactate content (r = 0.88, P less than 0.01). In summary, patients on HD had a lower muscle total carnitine content than control subjects which was correlated to exercise performance.(ABSTRACT TRUNCATED AT 250 WORDS)