Objectives: Nephrotoxicity of calcineurin inhibitors (CNI) in kidney allografts has been a significant problem even with low exposure regimens. On the other hand, CNI-free regimen with everolimus (EVR) bears higher risk of acute rejection or de novo donor specific antibody (dnDSA). The aim of this study was to analyze the effects of minimizing tacrolimus (TAC) to a 'very low dose' with concomitant use of both EVR and mycophenolate (MPA).

Methods: A group (n=25) of quadruple induction with very low TAC (target trough level (C₀) of 2.0-3.0 ng/mL), MPA (target-AUC_0-12 of 40 [micro]g^.hr/mL) and EVR (target C₀ of 4.0 ng/mL) was compared to the conventional group (n=46) with standard triple regimen with low TAC (target C₀ of 4-6 ng/mL and MPA (target-AUC_0-12 of 60 [micro]g^.hr/mL). Both groups were given 2 doses of basiliximab (20mg). Protocol biopsy was taken at 1, 3, 6 and 12 months posttransplant. TAC-C₀, estimated glomerular filtration rate (eGFR, ml/min/1.73m²), urine protein (uP, g/day), hemoglobin (g/dL), incidence of biopsy-proven CNI nephrotoxicity (CNIN) and acute rejection (BPAR), microvascular inflammation (MVI, glomerulitis and/or peritubular capillaritis), dnDSA, CMV infection, use of statins, lymphatic complication and stomatitis were compared at the time of biopsy between the groups.

Results: TAC levels were kept significantly lower in the quadruple group throughout the study period. The incidence of CNIN was significantly lower in the quadruple group (5% vs 24%). eGFR at 12m was significantly higher in the quadruple group. uP, hemoglobin were comparable. The incidence of BPAR and CMV infection was significantly lower in the quadruple group (8% vs 30% and 12% vs 35%, respectively). There was no MVI or dnDSA development in the quadruple group whereas they were observed in 9% and 2% of the conventional group. The incidence of lymphatic complication was comparable but stomatitis and use of statin was more frequent in the quadruple group.

Conclusions: Induction immunosuppression with addition of EVR to the conventional TAC/MMF regimen enabled safe reduction of TAC exposure with reduced nephrotoxicity profile, better graft function, reduced incidence of BPAR and CMV infection, without any increase in the incidence of MVI or dnDSA.

CITATION INFORMATION: Miura M, Higashiyama H. Quadruple Induction Regimen with Basiliximab, Everolimus, Mycophenolate and Very Low Dose Tacrolimus Improves Graft Function without Increase in the Incidence of Microvascular Inflammation or De Novo Donor Specific Antibody Compared to the Standard Triple Regimen. Am J Transplant. 2016;16 (suppl 3).

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