Association between resistance to erythropoiesis-stimulating agents and carnitine profile in patients on maintenance haemodialysis

Abstract

Objective: Patients on dialysis are in a chronic carnitine-deficient state. This condition may be associated with abnormalities in fatty acid and organic acid metabolism; however, the details are unknown. We investigated the association between carnitine profiles before and after dialysis and the erythropoiesis-stimulating agent (ESA) resistance index (ERI), which is a significant prognostic factor in patients on maintenance haemodialysis.

Methods: This was a cross-sectional study. We measured the carnitine profile of 79 patients on maintenance haemodialysis before and after dialysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The associations between the ERI and pre-dialysis carnitine profile, removal rate of various carnitines, and previously-reported ERI-related factors were investigated. Significant factors were determined with stepwise multiple regression analysis and validated with the bootstrap method. SPSS version 22.0 was used for analysis, and P < 0.05 was considered statistically significant.

Results: The removal rate of long-chain acylcarnitine with dialysis was lower than that of short-chain or medium-chain acylcarnitines. Stepwise multiple regression analysis (n = 79) demonstrated that 3-hydroxy isovalerylcarnitine (C5-OH, P < 0.001, β = -0.469) and stearoylcarnitine (C18, P < 0.001, β = 0.390) were independent significant factors (R² = 0.239) of ERI. The bootstrap method similarly indicated these two to be significant factors.

Conclusion: ERI positively correlated with long-chain C18 acylcarnitine and negatively correlated with short-chain C5-OH acylcarnitine. C5-OH and C18 acylcarnitines at baseline might be contributing factors in distinguishing responders from nonresponders after L-carnitine administration.

Keywords: acylcarnitine profile; anaemia; haemodialysis; metabolism; removal rate.