Abstract
Hemodialysis (HD) is a lifesaving treatment. Though, this therapy cannot correct medical conditions associated with advanced chronic renal failure. Previous studies showed that oxidative stress in HD patients, particularly with metabolic acidosis, increases RBC fragility. Hb after exceeding the capacity of the plasma detoxifying system can trigger many pathologic reactions like removal of NO, formation of reactive oxygen and lipid species, and redox state changes that induce many inflammatory and apoptotic genes. Hb is now considered as a progressive factor in ESRD. Hence, we studied ex vivo effects of Altra Flux Cellulose Diacetate Hemodialyzer (CHD) on removal of Hb under acidic (pH 6.8) and normal (pH 7.4) conditions. By monitoring inflammatory (ICAM-1, VCAM-1, P/E Selectin) and apoptotic responses of HCAEC exposed to the hollow fiber extracts, we also tested if Hb/pH may be involved in the removal of membranal compounds that might be cytotoxic. During 5 hours of HD, CHD was unable to completely clear Hb. The acidic pH slightly increased the removal of Hb but it triggered Hb oxidative degradation and albumin clearance. The low pH increased Hb autoxidation and conversion to ferryl species, and destabilized the heme-globin interface. The hollow fiber extracts activated HCAEC. While pH 7.4 extracts slightly increased endothelial inflammation, pH 6.8 extracts induced apoptosis. In summary, CHD were only partially effective in Hb clearance and their acidic extracts appeared toxic to HCAEC.
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