The influence of cytomegalovirus and Epstein-Barr virus serostatus on haemoglobin levels and erythropoietin-stimulating agent responsiveness in patients on the transplant list with stage 5 chronic kidney disease

Cytomegalovirus (CMV) seropositivity has been reported to be a major determinant of erythropoietin-stimulating agent (ESA) resistance in patients with chronic kidney disease (CKD). It is hypothesised that prior CMV infection induces significant changes in T-cell subtypes that promote bone marrow resistance to ESA. We examined whether CMV or Epstein-Barr virus (EBV) serostatus influenced haemoglobin (Hb) levels and/or ESA resistance in our population of CKD stage 5 patients. Data on CMV and EBV serology, age, sex and Hb was collected on 1,417 patients presenting for a renal transplant from 2000 to 2009 in Ireland. Patients were split into four groups (CMVneg/EBVneg, CMVpos/EBVneg, CMVneg/EBVpos, and CMVpos/EBVpos) and analysis of variance was performed to examine whether CMV and EBV serostatus influenced Hb levels pre transplantation. Data was then collected on 117 patients currently on the transplant pool from Beaumont and Tallaght Hospitals. CMV and EBV serostatus, Hb, ESA dose and other parameters associated with ESA responsiveness (iron studies, B12/folate, albumin, PTH, diabetes, vascular access, dialysis adequacy) were collected. Multivariate analysis was performed to determine factors associated with increased ESA dosage. CMV positivity was found to have no effect on Hb levels or ESA dosage. Likewise, EBV serostatus had no effect on these parameters. First, analysis of 1,417 patients showed no difference in mean Hb between the various CMV/EBV serostatus groups. Second, analysis of patients currently on the transplant pool also showed that there was no difference in mean Hb between CMV and EBV groups. Analysis of a subpopulation of haemodialysis patients alone showed that CMV positivity was associated with a higher mean Hb and a lower mean ESA dose. Our results contrast with those of a recent report by Betjes et al. linking ESA resistance to CMV seropositivity. No association was found between CMV or EBV serostatus and Hb levels or ESA dosage. CMV seropositivity is not associated with increased ESA requirements in our population. These conflicting results may be due to differences in patient demographics and a lower target Hb level in our study.