Incidence of recombinant erythropoietin (EPO) hyporesponse, EPO-associated antibodies, and pure red cell aplasia in dialysis patients

Abstract

Background. Since 1998, an increase of anti-erythropoietin (anti-EPO) antibody-induced pure red cell aplasia (PRCA) has been reported. As data up to now consisted mostly of spontaneously reported cases the question arose about the frequency of this increase in EPO-induced PRCA. The objectives of this study were to determine the incidence and causes of recombinant EPO hyporesponse, of antibodies to EPO in patients on dialysis, and to relate the detection of anti-EPO antibodies to the presence of PRCA. Method. This multicenter cohort study used existing patient data and serum samples collected at 6-month intervals from 1677 patients with incident end-stage renal disease (ESRD) participating in The Netherlands Cooperative Study on the Adequacy of Dialysis-2 (NECOSAD-2). Results. Fifty-seven patients had an inadequate EPO response, which resulted in an incidence of 16.7 per 1000 patient-years on EPO while on dialysis. All available sera specimens (N = 232) of these patients were screened for anti-EPO antibodies. The sera specimens of two of these 57 patients tested positive. Of the 57 patients with inadequate EPO response, one had clinical PRCA (incidence 0.29 per 1000 patient-years on EPO and on dialysis). Of the 1346 patients without symptoms of inadequate EPO response, one patient tested borderline positive for anti-EPO antibodies. In total, three patients developed EPO antibodies during follow-up, leading to an estimated incidence of 1.27/1000 (95% CI 0.3 to 3.7/1000) patient-years since the start of dialysis. Conclusion. The incidence of inadequate EPO response in our population of dialysis patients is in concordance with tentative calculations found in the literature. Furthermore, we found the incidence of EPO-induced PRCA and EPO antibodies to be low. © 2005 by the International Society of Nephrology.