ESOT 2013: Outcomes with tacrolimus-based immunosuppression after kidney transplantation with standard or extended-criteria donor organs: the OSAKA study

Bernhard Banas, Regensburg, Germany – Prolonged-release tacrolimus administered once-daily provides high rates of graft survival and reduction in biopsy-confirmed acute rejection (BCAR), with a manageable tolerability profile, in patients who receive kidney transplantations from extended-criteria (ECD) donors. An analysis under the Optimising Immunosuppression After Kidney Transplantation with Advagraf (OSAKA) study protocol shows that prolonged-release tacrolimus is as effective for preventing graft loss, BCAR and renal dysfunction as standard tacrolimus administered twice daily in both ECD and standard-criteria donor (SCD) kidney transplantations. The results were presented by Professor Bernhard Banas from the University Medical Center in Regensburg in Germany.

OSAKA was designed as a randomised, open-label, parallel-group Phase IIIb study in which 1,251 patients received either twice-daily tacrolimus at a starting dose of 0.2mg/kg/day (Arm 1) or once-daily tacrolimus 0.2mg/kg/day (Arm 2) or 0.3mg/kg/day (Arm 3) with mycophenolate mofetil (MMF) and corticosteroids over a study period of 24 weeks, or once-daily tacrolimus 0.2mg/kg/day with MMF, basiliximab and corticosteroids perioperatively (Arm 4). The primary efficacy endpoint was defined as a composite outcome of graft loss, BCAR or graft dysfunction (eGFR <40mL/min/1.73m²) at Week 24.

In total, 578 patients (48.2%) received SCD kidneys and 620 patients (51.8%) received ECD kidneys distributed similarly across the four arms. The primary composite endpoint was reached by 36.5% of SCD kidneys vs 52.9% of ECD kidneys (p=0.0001). Graft loss occurred in 5.0% of SCD kidneys vs 9.8% of ECD kidneys (P=0.002) and renal dysfunction in 27.9% of SCD kidneys vs 47.4% of ECD kidneys (P=0.0001). No significant difference was observed in the rates of BCAR. Professor Banas hypothesised that in addition to the favourable efficacy and tolerability outcomes achieved with once-daily tacrolimus in patients receiving ECD kidneys, long-term follow-up may reveal additional benefits over twice-daily tacrolimus in relation to greater ease of use and consistency of tacrolimus exposure.