Efficacy and safety outcomes among de novo renal transplant recipients managed by C2 monitoring of cyclosporine a microemulsion: results of a 12-month, randomized, multicenter study.

Background. The clinical benefits of C 2 monitoring of cyclosporine microemulsion have been demonstrated, but C 2 targets in renal transplant recipients during the first year require validation. Methods. MO2ART was a prospective, multicenter study of renal transplant recipients managed by C 2 monitoring of cyclosporine microemulsion with steroids and mycophenolate mofetil or azathioprine. Patients were randomized on day 3 to two groups, which were managed from month 3 with higher or lower C 2 target ranges (months 4-6, 1,0001,200 ng/mL vs. 800-1,000 ng/mL; months 7-12, 800-1,000 ng/mL vs. 600-800 ng/mL, respectively). The primary endpoint was the glomerular filtration rate (GFR) at month 12. Results. A total of 296 patients were recruited, of whom 250 remained in the study at 3 months (higher-C 2 , n=131; lower-C 2 , n=119). GFR at 12 months did not differ between the higher- and lower-C 2 groups (65±17 mL/min vs. 66±14 mL/min). When patients were regrouped according to C 2 achieved by months 8 to 12, those with the lowest C 2 (<700 ng/mL) showed the lowest GFR at month 3 and the most pronounced increase in GFR between month 3 and month 12 (P=0.04). Five episodes of biopsy-proven acute rejection occurred after month 3 (higher-C 2 group, n=2; lower-C 2 group, n=3). The overall 12-month Kaplan-Meier incidence of biopsy-proven acute rejection was 13.7%. Patient and graft survival were 93% and 89%, respectively, at 12 months. Conclusion. Both C 2 target ranges investigated showed excellent and nearly equivalent outcomes at 12 months. The decision to target the higher or lower end of these C 2 ranges should be made on an individual basis, taking into account patient and graft characteristics, and co-medication.