Oxidative damage to RBC membranes and pentose phosphate shunt activity in hemodialysis patients after suspension of erythropoietin treatment.

Abstract

During follow-up of anemic hemodialysis patients (HDP) treated with recombinant human erythropoietin (rHuEpo), it was noticed that in five HDP, some time after suspension of rHuEpo, hemoglobin (Hb) levels remained at acceptable levels. A metabolic block of the pentose phosphate shunt (PPS) has been described in HDP, which leads to increased oxidative damage of red blood cell (RBC) membranes and increased susceptibility to hemolysis. The increased production of short-chain fatty aldehydes, including malonyldialdehyde (MDA), is an appropriate index of oxidative damage. This study aimed to verify whether the maintenance of acceptable levels of Hb was related to a change in RBC membrane oxidative damage and pentose phosphate shunt activity. In the five HDP in question who required rHuEpo (150 U/kg/week) for severe anemia (Hb = 7.48 +/- 0.95 g/dl), after a stable level of Hb > 10 g/dl was reached for at least 1 month, rHuEpo treatment was stopped. Hb levels remained adequate (Hb = 10.68 +/- 0.77 g/dl) after 14.6 +/- 7.64 months. The oxidative damage was evaluated by measuring RBC MDA (microgram/ml packed RBC) basal levels, and PPS activity by measuring MDA levels after incubation with ascorbate and cyanide (delta % RBC MDA production). Ten anemic HDP not treated with rHuEpo were used as controls (Hb = 8.12 +/- 1.32 g/dl). It was found that the maintenance of adequate levels of serum Hb after suspension of rHuEpo therapy is related to a decrease in RBC membrane oxidative damage (RBC MDA HDP = 2.40 +/- 0.41 vs. RBC MDA controls = 18.23 +/- 6.56; P < 0.005) in consequence of the normalization of pentose phosphate shunt activity.