Introduction: Lack of long term follow-up data and wound healing issues reported in early clinical experiences are still limiting de novo use of Everolimus (EVR) in combination with reduced-exposure of Tacrolimus (EVR+rTAC). We present our prospective, randomized clinical study in 100 renal transplant recipients (RTR) who completed the first 5 years follow-up.
Methods: One hundred renal transplant recipients were randomized to receive once-daily manteinance low dose EVR (3-5 ng/ml) plus rTAC (3-5 ng/ml) vs standard TAC+MMF regimen, with Thymoglobuline induction in both study groups. Usual clinical data were analized, including detailed description of early wound healing adverse events and surgical complications.
Results: At 5 year follow-up no differences were found in patient survival (EVR 93% vs MMF 91%, p=ns) and death censored graft survival (EVR 96% vs MMF 95%, p=ns), as well as renal function (aMDRD ml/min: EVR 54.6 vs 49.6, p= ns). Early surgical complications (within 30 days) were also not significantly different in the two groups: EVR+rTAC 20% vs MMF+TAC: 17%. The analysis of the severity of surgical complications with the Clavien-Dindo classification, found no significative differences in the severity of complications: EVR+rTAC: classl #5, class 2 #1, class3 #4; MMF+TAC: classl #4, class 2 #0, class3 #5. Significantly lower acute rejection rate was found in the EVR group (EVR 3% vs MMF 11%, p<0.029). Also lower PCR-DNA-CMV infections were observed in TAC+EVR vs TAC+MMF combination (PCR-DNA-CMV: EVE 38% vs MMF 70%, p<0.004). Exposure to Tacrolimus blood levels was also significantly lower in KTx receiving rTAC+EVE compared to those receiving TAC+MMF (TAC through levels ng/ml: EVR 4.1 +/- 0.9 vs MMF 5.7+/-1.3 ng/ml).
Conclusions: Our data show the safety and efficacy of long-term immunosuppression in renal transplant recipients with the combination of EVR plus low dose TAC, with significantly lower CMV infections, respect to the standard TAC plus MMF immunosuppression. Our data also indicate that wound healing problems, as observed in the early studies with high exposure to mTOR inhibitors, can be prevented with current low exposure to Everolimus in combination with reduced exposure to Tacrolimus.