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Background/Aims: The mechanism of muscle cramp in hemodialysis patients is not well understood. Leptin, a middle molecule uremic toxin, is able to affect neuronal activity. This study aimed to determine the association between leptin and hemodialysis-related muscle cramps. Methods: A total of 79 hemodialysis patients were enrolled. The episodes of hemodialysis-related muscle cramps were recorded over a 28-day period. Serum levels of leptin were measured on the 15th day, a mid-week dialysis session. Results: Frequent hemodialysis-related cramps were associated with old age and elevated serum leptin levels. The risk of frequent hemodialysis-related cramps increased with increasing tertiles of leptin concentration. This relationship remained significant after adjustment for age, mean ultrafiltration ratio, gender, body mass index, insulin, resistin, c-reactive protein, albumin, peripheral arterial disease, electrolytes, and β2-microglobulin. Conclusion: Leptin levels are associated with frequent hemodialysis-related cramps. Further studies are necessary to elucidate the underlying mechanisms. [ABSTRACT FROM AUTHOR]