Introduction: Low acute rejection rates limit the evaluation of new agents, resulting in the recommendation of composite endpoints to assess efficacy failure (EMA 2008: patient death/graft loss or acute rejection [BPAR] or renal dysfunction). OSAKA, the first study to use this endpoint, showed donor age as the most important risk factor for reaching the individual and composite endpoints1. The present analyses investigate different thresholds of eGFR on the composite endpoint. Methods: Renal-transplant recipients were randomized to tacrolimus immediate release (BID) 0.2mg/kg, tacrolimus prolonged release (QD) 0.2mg/kg, QD 0.3mg/kg or QD 0.2mg/kg plus basiliximab. All patients received MMF, and steroids except the steroid-free arm QD 0.2mg/kg plus basiliximab. Patients who underwent primary or re-transplant, received a living or deceased-donor organ using standard and expanded kidney criteria were included. As per the original protocol, graft dysfunction was defined at 24 weeks post-transplant as eGFR < 40mL/min/1.73m2. The composite endpoint was recalculated using eGFR = < 30, < 40, < 50 or < 60 mL/min/1.73m2. Results: Treatment group demographics were well balanced with a higher proportion of organs from deceased male donors < 60 years, 50% were ECDs reflecting the European transplant population. 1198 patients provided data for the eGFR analyses. The composite endpoint, per protocol, for all patients was 45.0% (7.5% graft loss, 13.2% BPAR, 38.0% eGFR < 40) and similar across groups. Progressively raising the eGFR threshold from < 30 to < 60mL/min/1.73m2 resulted in an increasing proportion of patients contributing to the efficacy failure rate: dysfunction 18.0, 38.0, 58.9, 78.8% and composite endpoint 28.4, 45.0, 62.9, 80.9% of patients, respectively. Pair-wise comparison revealed highly significant (p< 0.0001 Chi-2 test) differences for the composite endpoint between successive thresholds of eGFR (Figure).[Figure 1]Conclusions: In a typical European transplant study population, renal dysfunction was the main driver of the composite endpoint, and the failure rate was highly dependent upon eGFR threshold. As graft function declines with increasing donor age, selection of a threshold of dysfunction that is too high, might obscure clinically significant changes in less frequently reached endpoints of survival and rejection. Moreover, study design should carefully consider donor and recipient characteristics not least donor age, expanded criteria, and mismatches to assure analysis of the properties of immunosuppressive protocols, which are representative of real-life clinical practice.