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Carnitine not only serves as a transporter, shuttling free fatty acids (FFAs) into the mitochondria, but it also plays a crucial role in essential lipid metabolism processes within the mitochondria, including beta oxidation.
Dialysis-related carnitine disorder (DCD), which causes a variety of symptoms, has been known for approximately 50 years. Possible factors include removal through dialysis therapy, decreased synthesis due to loss of renal function, changes in dietary content, and effects of dialysis therapy on lipid metabolism; but these factors remained unclear.
The effects of dialysis therapy on lipid metabolism include acetic acid, which is contained in the dialysate, and heparin, which is used as an anticoagulant. Serum carnitine concentrations in different dialysate have been reported, but the association with anticoagulants remained unknown.
The anticoagulants’ unfractionated heparin (UH) and low molecular weight heparin (LH) have different effects on FFA, with UH having a smaller effect on FFA metabolism compared to LH.
This study aimed to elucidate the effects of the differences in lipid metabolism between UH and LH on carnitine metabolism and explore the causes of DCD.
This retrospective investigation used medical records to assess the anticoagulant regimens of patients since hemodialysis (HD) initiation. We enrolled patients who had continuously received either UH or LH since the initiation of HD based on the results. This study excluded individuals who received carnitine supplementation within the preceding 12 months, were <20 years of age, with a history of gastrointestinal surgery or malignant tumors, and declined consent for study participation.
We investigated the acylcarnitine/free carnitine ratio (AC/FC ratio) in a group of patients who continued to use UH (UH group; n = 25) and LH (LH group; n = 19). Further, we evaluated the effect of UH administration on carnitine metabolism and measured serum FFAs before and after an HD session in individuals from the UH group. Furthermore, we examined the AC/FC ratio before and 3 months after changing anticoagulants in the group that switched from LH to UH (LU group; n = 7) and those that continued LH (LL group; n = 8).
Notably, the AC/FC ratio indicates the state of carnitine at the cellular level, and the higher the value the more carnitine deficiency is indicated at the cellular level.
AC/FC was significantly higher in the UH group (UH group: 0.697 ± 0.158; LH group: 0.560 ± 0.195; p = 0.012). Additionally, serum FFAs in that group increased to 0.825 ± 0.270 after dialysis from 0.172 ± 0.160 which was before dialysis, indicating a positive correlation with AC/FC. Furthermore, before the anticoagulant change, AC/FC was 0.596 ± 0.179 in the LU group and 0.576 ± 0.221 in the LL group, with a nonsignificant difference. However, three months after the anticoagulant change, AC/FC in the LU group (0.733 ± 0.223) considerably outperformed AC/FC in the LL group (0.498 ± 0.190, p = 0.0279).
Compared with UH, LH has a lesser effect on lipid metabolism, indicating that it also has a lesser effect on carnitine metabolism.