Antibodies to Erythropoietin Are Associated with Erythropoietin Resistance in Hemodialysis Patients in KwaZulu-Natal (South Africa)

Abstract

Recombinant human erythropoietin (rHuEPO) is a glycoprotein and biological equivalent to the endogenous compound administered to treat anemia of end-stage renal disease patients. Resistance to rHuEPO has been reported, whereby patients require higher and higher doses of rHuEPO to maintain an adequate hemoglobin level. In this study, assessment of native and administered erythropoietin (EPO), antibody and hemoglobin levels was carried out on a sample of patients with renal failure on hemodialysis (HD). This is a randomized controlled trial where consecutive subjects attending HD units at Addington Hospital and King Edward Hospital, Durban (South Africa) were included until the target number was reached. Forty patients with renal failure on HD and receiving recombinant EPO Beta (Recormon) for treatment of anemia via the subcutaneous route in weekly doses of 2000 IU, 4000 IU, 6000 IU, 8000 IU, 12,000 IU, or 18,000 IU according to the severity of the anemia were included after obtaining informed consent. Also included in the study were 10 HD patients not on rHuEPO therapy and 10 healthy individuals from the Durban University of Technology, recruited as described above to form the control group. ELISA was used to measure serum levels of EPO as well as antibodies to EPO. Results were analyzed by descriptive, inferential methods and by logistic regression analysis using IBM SPSS Statistics for Windows version 22.0. Antibodies to EPO were found in almost all patients who were receiving EPO. The highest levels of antibody to EPO were found to be associated with patients receiving the highest weekly dose of EPO (18,000 IU). Logistic regression analysis also revealed that serum levels of EPO, gender or age were not associated with any significant variation of serum antibody level. High levels of serum antibodies to EPO are a risk factor for EPO resistance.