Cyclosporine Profiling With C 2 and C 0 Monitoring Improves Outcomes After Heart Transplantation

Abstract

Cyclosporine (CsA) level at 2 hours post-dose (C2) is a more sensitive marker for rejection risk than trough (C0) level. A combination of C2 and C0 monitoring may prove optimal. We compared efficacy and safety outcomes among 28 de novo heart transplant patients in whom both C2 and C0 monitoring were undertaken (Group 1), with a single CsA profile at Weeks 2 to 6, versus 28 historic controls monitored by only C0 (Group 2). Patients received anti-thymocyte globulin (ATG) induction with CsA, steroids and azathioprine maintenance therapy. The CsA microemulsion dose was significantly higher in Group 1 than Group 2 up to 3 months post-transplant. Mean C2 values in Group 1 at 3 and 12 months were 1,248 +/- 328 ng/ml and 1,039 +/- 362 ng/ml, respectively. One patient in Group 1 and 7 in Group 2 (25%) discontinued CsA, either due to CsA-related neurotoxicity or two or more episodes of early rejection. At 12 months, graft and patient survival were 100% in both groups. Six patients in Group 1 (21%) and 11 in Group 2 (39%) had at least one episode of biopsy-proven acute rejection (not significant). Over the first 12 months post-transplant, the proportion of biopsies showing Grade 3 rejection was 5% in Group 1 and 11% in Group 2 (p < 0.002). Gloerular filtration rate (GFR) was significantly lower in Group 1 than Group 2 at both 3 and 12 months. Combined use of C2 and C0 monitoring results in improved efficacy versus C0 monitoring alone. Regular measurement of C2 levels should be undertaken in de novo heart transplant recipients.