Blood free carnitine level is an independent determinant of erythrocyte membrane homogeneity and osmotic resistance in maintenance hemodialysis patients

Abstract Background Carnitine deficiency is highly prevalent in chronic maintenance hemodialysis (HD) patients and is implicated in erythropoietin resistance and impaired cell survival. However, whether carnitine status directly influences red blood cell (RBC) membrane properties independently of clinical confounders remains unproven. We evaluated systemic carnitine profiles, RBC osmotic fragility, and cell fragmentation to clarify their independent relationships. Methods In this prospective study of 29 maintenance HD patients, blood carnitine fractions (free carnitine [FC], total carnitine, and acylcarnitine) were measured. RBC osmotic fragility was evaluated using a 96-well microplate-based Parpart assay, and individual hemolysis curves were fitted to a two-parameter sigmoidal regression model to extract curve slope ( a , reflecting membrane homogeneity) and 95% complete hemolysis concentration ( x comp ). Fragmented RBCs (fragmented RBC percentage [FRC%]) and the erythropoiesis-stimulating agent (ESA) resistance index were simultaneously evaluated. Multivariable linear regression and model selection analyses were conducted, adjusting for age, sex, and HD duration. Results Systemic carnitine depletion (absolute or probable) was observed in 89.6% of patients. Multivariable linear regression demonstrated that higher blood free carnitine (FC) levels were independently and significantly associated with an increased osmotic fragility curve slope a ( P < 0.05). Model selection confirmed FC as the primary predictor. FRC% positively correlated with slope a ( ρ = 0.398, P = 0.032), and x comp positively correlated with the ESA resistance index ( ρ = 0.474, P = 0.047). Conclusions Blood FC sufficiency is an independent determinant of RBC membrane homogeneity and osmotic fragility in chronic HD patients. Optimizing carnitine status may serve as a promising strategy to preserve erythrocyte quality and improve renal anemia management.