Association of carnitine levels with muscle status, fatigue, and mortality in hemodialysis patients

BACKGROUND: Carnitine deficiency is prevalent among hemodialysis patients and may contribute to poor outcomes. In this study, we investigated the relationship of plasma carnitine and carnitine excretion with muscle status, fatigue, and mortality. METHODS: Plasma concentrations of free carnitine and acylcarnitines (AC) were measured using tandem mass spectrometry, and total carnitine concentration and acylcarnitine/free carnitine ratio were calculated. Daily carnitine excretion was estimated from complete collections of intradialytic dialysate and interdialytic urine. Muscle status was assessed by skeletal muscle index and muscle strength. Skeletal muscle index represents muscle mass and was derived from combined dialysate and urinary creatinine excretion; muscle strength was measured using handgrip strength. Fatigue was assessed through a questionnaire. RESULTS: In 59 hemodialysis patients (mean age 65 years, 37% female, median dialysis vintage 15 months), pre-dialysis plasma free carnitine was 20 [16-26] μmol/L, acylcarnitine was 13 [10-15] μmol/L, acylcarnitine/free carnitine ratio 0.6 [0.5-0.7], and daily carnitine excretion was 237 [192-276] μmol/24 h. In linear regression analyses, plasma total carnitine and free carnitine concentrations and daily carnitine excretion were associated with muscle status. Acylcarnitine/free carnitine ratio was associated with fatigue. During a median follow-up of 22 months, 27% of patients died. Higher daily carnitine excretion was independently associated with a lower risk of mortality. CONCLUSION: In hemodialysis patients, better muscle status was associated with higher plasma carnitine and daily carnitine excretion, while fatigue was associated with higher acylcarnitine/free carnitine ratio. Higher daily carnitine excretion was independently associated with lower mortality. Daily carnitine excretion represents a novel biomarker for assessing carnitine adequacy in this population and warrants further investigation.