Increased susceptibility to erythrocyte C5b-9 deposition and complement-mediated lysis in chronic renal failure

Background. Decreased red blood cell survival contributes to the anemia of chronic renal failure patients. Because patients on chronic dialysis therap y are frequently exposed to excessive complement activation, we investigate d the susceptibility of this patient population to erythrocyte C5b-9 deposi tion, complement-mediated lysis, and ghost formation. Methods. We developed a flow cytometric assay using antibodies to both glyc ophorin and the C5b-9 complex to detect C5b-9 deposition on intact erythroc ytes and erythrocyte ghosts. Serum C5b-9 levels and C5b-9 deposition on ery throcyte ghosts were measured by enzyme-linked immunosorbent assay. Results. A significant increase in C5b-9 deposition on intact erythrocytes was demonstrated in patients with advanced chronic renal failure (2.2 +/- 0 .5%) and in patients on chronic maintenance hemodialysis (2.3 +/- 0.4%) com pared with normal volunteers (0.9 +/- 0.1%, P = 0.005 vs. chronic renal fai lure, P < 0.001 vs. chronic hemodialysis patients). There was also a signif icantly higher percentage of C5b-9-positive erythrocyte ghosts in patients with advanced chronic renal failure (20.6 +/- 5%) and in chronic hemodialys is patients (15.5 +/- 3.1%) compared with normal controls (2.6 +/- 0.9%, P less than or equal to 0.001 vs, advanced chronic renal failure and chronic hemodialysis patients). Treatment of erythrocyte preparations with cobra ve nom factor, which activates the complement cascade, resulted in dramatic in creases in the percentages of C5b-9-positive erythrocyte ghosts in patients with chronic renal failure (49.9 +/- 6.9%) and in chronic hemodialysis pat ients (45.0 +/- 4.2%) compared with normal volunteers (22.3 +/- 2.7%, P < 0 .001 vs. chronic renal failure and chronic hemodialysis patients). Erythroc yte membrane expression of the complement regulatory proteins CD59 and CD55 did not significantly differ between normal controls and hemodialysis pati ents. Plasma C5b-9 levels after cobra venom factor stimulation were higher in chronic renal failure patients (535 mu g/ml) compared with normal contro ls (345 mu g/ml, P < 0.001). Conclusions. Patients with chronic renal failure and on hemodialysis therap y are susceptible to erythrocyte C5b-9 deposition with subsequent lysis and ghost formation. Susceptibility to complement-mediated erythrocyte injury may contribute to the anemia of chronic renal disease.