CD30, a member of the tumor necrosis receptor superfamily, is strongly expressed on activated lymphocytes. The ectodomain shedding of CD30 results in soluble CD30 (sCD30) that may serve as a prognostic serum marker of outcomes in kidney transplantation (Tx). In a previous study (Grenzi et al, 2016), we observed that de novo kidney transplant recipients (R), converted at month-3 post-Tx from tacrolimus (TAC) to sirolimus (SRL), had significant lower sCD30 levels in comparison with patients maintained with TAC, in different samples collected up to 24 months post-Tx. To further investigate the influence of these drugs on sCD30 serum levels, in the present study we tested samples collected on days 7, 90, 180 and 365 post-Tx in 288 R, randomized to receive antithymocyte globulin, TAC (low dose) and everolimus (r-ATG/EVR, n=85); basiliximab, TAC (low dose) and EVR (BAS/EVR, n=102); or basiliximab, TAC and mycophenolate (BAS/MPS, n=101). All patients received prednisone. Serum sCD30 levels were significantly lower in R treated with EVR, even when combined with reduced doses of TAC (r-ATG/EVR and BAS/EVR), in comparison with BAS/MPS-treated R (p<0.0001, two-way ANOVA). As the CD30 molecule can also be induced as a result of viral infection, we evaluated whether sCD30 levels were also associated with CMV infection/disease, under different immunosuppression regimens and without CMV pharmacological prophylaxis. We observed that treatment with EVR (negative association), recipient age, pre-Tx IgG CMV positivity of the R, and sCD30 levels were independently associated with CMV infection/disease. There were no significant differences in sCD30 levels regarding acute rejection, graft function or survival. In vitro experiments where allogeneic stimulated CD30+ lymphocytes were treated with EVR and TAC, alone or in combination, confirmed that EVR treatment diminished the release of the sCD30, even in the presence of TAC. In conclusion, the present study confirmed the strong influence of mTOR inhibitors on sCD30 shedding and showed that, irrespectively of the type of immunosuppressive regimen, sCD30 serum levels are associated with occurrence of CMV infection.