Abstract / Summary
Abstract Background Carnitine deficiency is highly prevalent in chronic maintenance hemodialysis (HD) patients and is clinically implicated in erythropoietin resistance and impaired cell survival. However, whether carnitine status directly governs red blood cell (RBC) membrane properties independently of major clinical confounders remains unproven. We aimed to evaluate systemic carnitine profiles, RBC osmotic fragility, and physical cell fragmentation to clarify their independent relationships. Methods In this prospective observational study of 29 maintenance HD patients, blood carnitine fractions (free carnitine [FC], total carnitine, acylcarnitine) were quantitatively 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 ). Automated fragmented RBCs (FRC%) were simultaneously quantified. Multivariable linear regression models adjusted for age, sex, HD duration, C-reactive protein (CRP), and type 2 diabetes mellitus (T2DM). Results Systemic carnitine depletion was widespread, with 89.6% of patients meeting the criteria for absolute (24.1%, FC < 20.0 µmol/L) or probable (65.5%, FC 20.0–36.0 µmol/L with acylcarnitine/FC ratio ≥ 0.4) carnitine deficiency. Multivariable linear regression analyses demonstrated that higher FC levels were independently and significantly associated with an increased OFT slope a (Model 1A [adjusted for age, sex, HD duration, CRP]: β = 0.6090, P = 0.036; Model 1B [Model 1A + T2DM]: β = 0.5970, P = 0.045) and a higher x comp (Model 2A: β = 0.0009, P = 0.042; Model 2B: β = 0.0009, P = 0.041), irrespective of clinical confounders. FRC% exhibited a significant positive correlation with slope a (ρ = 0.398, P = 0.032), reflecting dynamic intravascular selective destruction of fragile cells. In ESA-treated patients (n = 18), x comp correlated with the ESA resistance index (ρ = 0.474, P = 0.047) and maintained a consistent positive linear relationship in adjusted models (β = 0.327–0.356). Conclusions Blood FC sufficiency is an independent determinant of RBC membrane homogeneity and complete hemolysis resistance in chronic maintenance HD patients. Monitoring and optimizing systemic carnitine status represents a promising adjunctive therapeutic strategy to preserve erythrocyte quality and enhance renal anemia management.