Two prospective, randomized studies evaluated everolimus 1.5 vs. 3 mg/day with steroids and lowexposure cyclosporine (CsA) (C 2 monitoring) in de novo renal transplant patients. Everolimus dosing was adjusted to maintain a minimum trough level of 3 ng/mL. Study 1 (A2306; n = = 237) had no induction therapy; in Study 2 (A2307; n = = 256) basiliximab was administered (Days 0 and 4). The primary endpoint was renal function at 6 months. CsA C 2 target levels, initially 1200 ng/mL in Study 1 and 600 ng/mL in Study 2, were tapered over time post-transplant. Median creatinine levels in Study 1 were 133 and 132 lmol/L at 6 months in the 1.5 and 3 mg/day groups, respectively, and 130 lmol/L in both groups in Study 2. Biopsyproven acute rejection (BPAR) occurred in 25.0% and 15.2% of patients in the 1.5 and 3 mg/day groups in Study 1, and 13.7% and 15.1% in Study 2. Incidence of BPAR was significantly higher in patients with an everolimus trough < < 3 ng/mL. There were no significant between-group differences in the composite endpoint of BPAR, graft loss or death, nor any significant between-group differences in adverse events in either study. Concentration-controlled everolimus with lowexposure CsA provided effective protection against rejection with good renal function.

Cytomegalovirus infection after transplantation and living with cats increased the risk of VL in renal transplant recipients living in VL endemic areas.

Summary The proliferation signal inhibitor everolimus (Certican), has demonstrated efficacy with full‐dose cyclosporine (CsA) (Neoral®). Two multicenter randomized controlled studies were performed to compare 12‐month efficacy and safety of everolimus 1.5 and 3.0 mg/day with reduced‐dose CsA. Study 1 enrolled 237 de novo renal allograft recipients, randomizing 222 nonblack patients to either everolimus 1.5 or 3.0 mg/day, with the Neoral® dose guided by C2 (monitoring of CsA concentration 2 h after dosing). Study 2 had a similar protocol, with basiliximab included, enrolling 256 recipients and randomizing 243 nonblack patients. In Study 1, there was a lower incidence of acute rejection in nonblack patients on 3 mg/day (16.4%) compared with 1.5 mg/day (25.9%), P = 0.08. In Study 2, the inclusion of basiliximab lowered the overall incidence of acute rejection; 14.3% of nonblack patients (3 mg/day) and 13.6% of nonblack patients (1.5 mg/day) had acute rejection by 12 months (P =0.891). Renal function was preserved throughout the study, with no differences observed between groups within studies. Everolimus was well tolerated with no significant differences between doses. Everolimus, in combination with reduced‐dose Neoral®, demonstrated efficacy and was well tolerated. Basiliximab allows for utilization of lower doses of everolimus with reduced dosing of Neoral®.

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