Erythrocyte Membrane Fatty Acid Remodeling and Zinc Protoporphyrin Alterations Associated with Anemia Severity in Hemodialysis Patients

Abstract

Background: This study investigated the relationship between erythrocyte membrane fatty acids, omega-3 index, and zinc protoporphyrin (ZnPP) levels in hemodialysis (HD) patients across hemoglobin-defined anemia severities. Methods: This prospective cross-sectional study included 117 chronic HD patients and 28 healthy controls. ZnPP was measured by high-performance liquid chromatography, and erythrocyte membrane fatty acids by gas chromatography-mass spectrometry. Results: HD patients showed a significantly lower omega-3 index than controls (p < 0.0001), although it did not differ across hemoglobin-defined groups (p = 0.589). Palmitic and erucic acid were higher, whereas oleic acid was lower, in patients with lower hemoglobin. In unadjusted analyses, hemoglobin correlated inversely with palmitic acid (r = -0.220, p = 0.017) and erucic acid (r = -0.183, p = 0.048), whereas the positive association with oleic acid (r = 0.451, p < 0.0001) remained significant after false discovery rate (FDR) correction. ZnPP increased as hemoglobin decreased (p = 0.013) and was negatively associated with hemoglobin (r = -0.406, p < 0.0001). Conclusions: HD patients with lower hemoglobin showed altered erythrocyte membrane fatty acid composition; among fatty acids, only the oleic acid-hemoglobin association remained significant after FDR correction. ZnPP rose as hemoglobin declined and was independently inversely associated with hemoglobin after multivariable adjustment (beta = -0.051, p < 0.0001), independent of any dichotomous reference definition, supporting ZnPP as a continuous marker of anemia severity and iron-restricted erythropoiesis in HD patients.