Evaluation of Recombinant Human Erythropoietin Responsiveness by Erythrocyte Creatine in Haemodialysis Patients

Background: One of the main causes of anaemia in patients with end-stage renal disease is relative deficiency in erythropoietin production. Recombinant human erythropoietin (rHuEpo), a potent haematopoietic growth factor, is used to treat anaemia in haemodialysis patients. The effect of rHuEpo is usually assessed by haematological indices such as red blood cell count, haemoglobin concentration and haematocrit, but erythrocyte indices do not provide information of the rapid change in erythropoietic activity. As erythrocyte creatine directly assess erythropoiesis, the aim of this study was to evaluate the effect of rHuEpo in haemodialysis patients by measuring erythrocyte creatine. Methods: rHuEpo dose was fixed 3 months prior to the enrollment and was maintained throughout the entire study period. Eerythrocyte creatine was measured with haematologic indices in 83 haemodialysis patients. Haemoglobin was also measured 3 months after. Results: rHuEpo dose (152.4±62.9 vs. 82.2±45.5 units/kg/week, P=0.0001) and erythrocyte creatine (2.07±0.73 vs. 1.60±0.41 µmol/gHb, p=0.0003) were significantly higher in 27 patients with haemoglobin <10g/dL compared to 56 patients with haemoglobin ≥10g/dL. There was a fair correlation between rHuEpo dose and erythrocyte creatine (r=0.55, P <0.0001). Increase in haemoglobin (>0.1g/dL) was observed in 37 patients, whereas haemoglobin did not increase in 46 patients. Erythrocyte creatine was significantly higher in patients with increase in haemoglobin compared to those without (2.04±0.64 vs. 1.52±0.39 µmol/gHb, p <0.0001). When 8 variables (rHuEpo dose, erythropoietin resistance index, C-reactive protein, intact parathyroid hormone, incidence of iron deficiency, presence of anaemia, erythrocyte creatine and reticulocyte) were used in the multivariate logistic analysis, erythrocyte creatine emerged as the most important variable associated with increase in haemoglobin (Chi-square=6.19, P=0.01). Conclusion: Erythrocyte creatine, a useful marker of erythropoietic capacity, is a reliable marker to estimate ameliorative effectiveness of rHuEpo in haemodialysis patients.