Risk factors and mediating mechanisms of restless legs syndrome in patients undergoing maintenance hemodialysis: a longitudinal cohort study combined with Mendelian randomization analysis

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Sarcopenia and depressive severity independently predicted 5-year incident restless legs syndrome (RLS) in patients on maintenance hemodialysis.
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Longitudinal models showed chronic depression, anxiety, frailty, and sarcopenia mediated significant risk pathways for RLS.
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Mendelian randomization confirmed lower estimated glomerular filtration rate (eGFR) causally associated with increased depression risk.
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Depression mediated a substantial indirect effect on suppressed dopamine metabolism, accounting for 41% of the total effect.
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The study highlights a cascade linking renal impairment, chronic phenotypic deterioration, and disrupted dopamine metabolism in RLS.

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