Erythropoiesis and Erythrocyte Age Distribution in Hemodialysis Patients Undergoing Erythropoietin Therapy

Abstract

Renal anemia is caused in part by a reduced life span of red blood cells (RBCs) and by reduced erythropoietin biosynthesis in the damaged kidney. The RBC age can be determined by density gradient centrifugation and estimation of cell-age-dependent enzyme activities, as aspartate aminotransferase. The RBC age distribution influences the median density (D50) of RBCs and the blood rheology in coherence with the hematocrit. In our study, the median density was determined by Percoll density gradient centrifugation in 18 healthy subjects (D₅₀ = 1.0674 ± 0.0016 g/ml) and in 14 hemodialysis patients (D₅₀ = 1.0674 ± 0.0016 g/ml in the course of recombinant human erythropoietin (rhEPO) therapy. During the first 4 weeks of therapy, a strong rejuvenation of RBCs was observed whereby the D₅₀ reached a minimum after 2 weeks (D₅o = 1.0655 ± 0.0022 g/ml; p < 0.05 vs. value before therapy) and a steady state after 4 weeks (D₅₀ = 1.0658 ± 0.0013 g/ml; p < 0.1 vs. value before therapy). In 5 of the patients with elevated plasma parathyroid hormone (i-PTH) concentrations > 10pmol/l, a significantly (p < 0.05) reduced amount of younger RBCs (D₅₀ = 1.0675 ± 0.0016 g/ml) was observed in the first 2 weeks of rhEPO therapy as compared to patients with i-PTH < 10 pmol/l (D₅₀ = 1.0677 ± 0.0019 g/ml). Thus, erythropoiesis in the early phase of rhEPO therapy is strongly influenced by elevated plasma i-PTH concentrations. Therefore, a gradual increase in rhEPO doses is preferable before therapy at elevated doses with an uncontrolled increase in RBC amount.

Changed Purine Nucleotide Concentrations and Enzyme Activities in Erythrocytes of Haemodialysis Patients Undergoing Erythropoietin Therapy

“…Aspartate aminotransferase in this study and in earlier studies of our group served as a marker enzyme for the age of erythrocytes. Erythrocyte density fractions of haemodialysis patients showed significantly higher aspartate aminotransferase activities (11) as an expression of reduced life span, which was demonstrated by means of 51 Cr experiments (3). In addition to an elevated aspartate aminotransferase 1 ) activitiy, erythrocytes of haemodialysis patients also exhibit elevated pyruvate kinase 1 ), hexokinase 1 ) and glucose-6-phosphate dehydrogenase 1 ) activities (20).…”

Red Blood Cell Density Distribution in Uremic Patients on Acetate and Bicarbonate Hemodialysis

“…Exoge nous EPO induces a rejuvenation of the red blood cell (RBC) distribution [10]. This reju venation is connected with a decrease in median density D50 and an increase in en zyme equipment (aspartate aminotransfer ase; GOT) of RBCs.…”