Effect of anti-thymocyte globulin on CMV infection in kidney transplant recipients: the risk is not increased in D+R- and depends on preformed cell-mediated immunity in R+

BACKGROUND: Rabbit antithymocyte globulin (rATG) induction is associated with profound immunosuppression, leading to a higher risk of cytomegalovirus (CMV) infection compared with anti-interleukin 2 receptor antibody (anti-IL-2RA). However, this risk, depending on the baseline CMV serological recipient/donor status, is still controversial. METHODS: The CMV DNAemia-free survival between rATG- and anti-IL-2RA-treated patients was analyzed in donor-positive/recipient-negative (D+R-) and recipient-positive (R+) patients in 1 discovery cohort of 559 kidney transplant recipients (KTRs) and 2 independent cohorts (351 and 135 kidney KTRs). The CMV-specific cell-mediated immunity (CMI) at baseline and at different time points after transplantation was assessed using an interferon γ enzyme-linked immunosorbent spot assay. RESULTS: rATG increased the risk of CMV DNAemia in R+ but not in D+R- KTRs. In R+ CMI-positive (CMI+) patients, the CMV DNAemia rate was higher in rATG-treated than in anti-IL-2RA-treated patients; no difference was observed among R+ CMI-negative (CMI-) patients. Longitudinal follow-up demonstrated a deeper depletion of preformed CMV CMI in R+ rATG-treated patients. CONCLUSIONS: D+R- KTRs have the highest risk of CMV DNAemia, but rATG adds no further risk. Among R+ KTRs, we described 3 groups, the least prone being R+CMI+ KTRs without rATG, then R+CMI+ KTRs with rATG, and finally R+CMI- KTRs. CMV serostatus, baseline CMV-specific CMI, and induction therapy may lead to personalized preventive therapy in further studies.