A randomized prospective study of tacrolimus sparing basiliximab induction with delayed everolimus addition in high-acuity liver transplantation.

BACKGROUND: Calcineurin inhibitors (CNIs) remain the cornerstone of immunosuppression after liver transplantation (LT) but contribute to chronic renal failure, increasing long-term morbidity and mortality. Strategies to minimize CNI exposure and preserve renal function are necessary to improve long-term outcomes in high-acuity LT recipients. METHODS: We conducted a single-center, prospective, randomized trial of adult LT recipients requiring pre-LT renal replacement therapy (RRT). Patients were randomized to: 1) basiliximab induction and delayed tacrolimus starting post-operative day (POD) 5 (BAS); 2) basiliximab induction, tacrolimus starting POD5, and everolimus starting POD31 followed by tacrolimus minimization (BAS-EVR); 3) standard immunosuppression (control). RRT independence, renal function, rejection, graft and patient survival, and adverse events were assessed. RESULTS: Seventy patients were analyzed (BAS n=30; BAS-EVR n=28; control n=12). Median MELD was 40 and 55.7% of patients required mechanical ventilation or vasopressor support pre-LT. Overall, 68.6% of patients achieved RRT independence by 24 weeks: 73.3% (BAS), 75.0% (BAS-EVR), and 41.7% (control). Basiliximab (p=0.04) and shorter duration of pre-LT RRT (p=0.02) were significantly associated with RRT independence; basiliximab remained significant after adjusting for duration of pre-LT RRT (OR 3.87, [95% CI 1.01 - 14.74], p=0.048). Among patients who achieved RRT independence, median eGFR trended higher in the BAS-EVR group (67 mL/min/1.73m2) than in BAS (52 mL/min/1.73m2) and control groups (50 mL/min/1.73m2) at 24 weeks. Patient and graft survival were comparable across groups. Adverse events were similar, although diarrhea (p=0.004) and acute kidney injury (p=0.01) were more frequent in the BAS-EVR group. CONCLUSION: Basiliximab induction therapy with delayed tacrolimus promotes RRT independence in high-acuity LT recipients. Addition of everolimus to minimize tacrolimus may further preserve renal function without compromising graft or patient survival.