1. 3. The ASCERTAIN Study

2. Source Holdaas H, Rostaing L, Serón D, et al. Conversion of long-term kidney transplant recipients from calcineurin inhibitor therapy to everolimus: a randomized, multicenter, 24-month study. Transplantation. 2011;92(4): 410–418.

3. Background Calcineurin inhibitor (CNI) therapy is known to induce nephrotoxicity in a dose-dependent manner. Nevertheless, improvements in graft function following elimination or reduction of CNI exposure in long-term kidney transplant recipients remains unclear. Furthermore, benefits of conversion from CNI to mammalian target of rapamycin inhibitor-based immunosuppression in long-term kidney transplant patients remain uncertain. The current study addressed this hypothesis.

4. Aim The ASCERTAIN study was undertaken to determine improvements in graft function in renal transplant patients with renal impairment following introduction of everolimus with elimination or minimization of CNI.

5. Methods

6. Key results Differences between CNI elimination (1.12 mL/min/1.73 m 2, 95% confidence interval [CI]: -3.51 to 5.76, P=0.63) and CNI minimization (0.59 mL/min/1.73 m 2, 95% CI: -3.88 to 5.07, P=0.79) vs controls at month 24 were non-significant. Post hoc analyses showed that patients with baseline creatinine clearance more than 50 mL/min had a significantly greater increase in measured GFR after CNI elimination vs controls. Adverse events resulted in discontinuation in 36 (28.3%) CNI elimination patients, 24 (16.7%) CNI minimization patients, and 5 (4.1%) controls (P<0.001 vs CNI elimination; P=0.020 vs CNI minimization).

7. Conclusion Conversion to everolimus with CNI elimination or minimization had no overall renal benefit and was associated with more frequent adverse events and discontinuations. Patients with a creatinine clearance of more than 50 mL/min may benefit from a change in therapy administered 6 months after renal transplantation. Conversion to everolimus with CNI elimination or minimization had no overall renal benefit.