Objectives: Nephrotoxicity of calcineurin inhibitors (CNI) in kidney allografts has been a significant clinical problem even with low exposure regimens. On the other hand, CNI-free regimen with everolimus (EVR) has been shown to have higher rate of acute rejection. The aim of this study was to analyse the effects of minimizing tacrolimus (TAC) dose to a 'very low dose' with both EVR and mycophenolate (MPA) in a steroid-free induction regimen.

Methods: A group (n=25) of quadruple induction with very low TAC (target-area-under-the-curve (AUC0-24) of 120 ng.hr/mL or trough level (C0) of 2.0 ng/mL), MPA (target-AUC0-12 of 40 ¯o;g.hr/mL) and EVR (target C0 of 4.0 ng/mL) was compared the other group (n=46) with conventional triple regimen with low TAC (target AUC0-24 of 180 ng.hr/mL or C0 of 5 ng/mL and MPA (target-AUC0-12 of 60 ¯o;g.hr/mL). Both groups were given 2 doses of basiliximab (20mg). Protocol biopsy was taken at 1, 3 and 6 months posttransplant. TAC-C0 and AUC0-24, estimated glomerular filtration rate (eGFR, ml/min/1.73m2), urine protein (uP, g/day), LDL-cholesterol (mg/dL), hemoglobin (g/dL), incidences of biopsy-proven CNI nephrotoxicity (CNIN) and acute rejection (BPAR), CMV infection, lymphatic complication and stomatitis were compare at the time of biopsy between the groups.

Results: TAC levels were kept significantly lower in the quadruple group after 1M. The incidence of CNIN was significantly lower in the quadruple group (0%). eGFR, uP, hemoglobin and LDL-cholesterol were comparable. The incidence of BPAR and CMV infection was significantly lower in the quadruple group (8% vs 30% and 12% vs 35%, respectively). The incidence of lymphatic complication or stomatitis was comparable.

Conclusions: Induction immunosuppression with addition of EVR to the standard TAC/MMF regimen enabled safe reduction of TAC exposure with reduced toxicity profile, reduced incidence of BPAR and reduced incidence of CMV infection.

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