C2 is superior to C0 as predictor of renal toxicity and rejection risk profile in stable heart transplant recipients

To assess whether cyclosporine A (CsA) 2-h peak (C2) is superior to trough levels (C0) for Neoral dose monitoring in heart transplantation (HT), we studied 928 C0-C2 paired determinations from 313 stable HT patients (257 male, aged 50 +/- 14 years at HT, follow-up 6.9 +/- 4 years), on a C0-based regimen. Our target C0 levels (ng/ml) were 150-400 (first 3 months), 150-300 (4-12 months), 100-250 (>12 months). Mean C0 and C2 levels were 268 +/- 80 and 1031 +/- 386, respectively (first 3 months); 230 +/- 49 and 955 +/- 239 For patients within the 157 +/- 53 and 745 +/- 236 (>12 months) (4-12 months).; target C0, the corresponding C2 were 600-1500 (first 3 months), 600-1300 (4-12 months), 400-1100 (>12 months). C2 correlated with C0 (r = 0.64, P = 0.0001). C2 correlated better with CsA dose than C0 (r = 0.41, P = 0.0001 vs. r = 0.33, P = 0.0001). Between patients, CsA dose varied by a factor of 9.3; the C/dose ratio varied by a factor of 8.5 for C2 and of 15.6 for C0. Patients with higher C2 (>740) had higher severe rejection score at 2 years (P = 0.02) than patients with lower C2. This did not apply to C0. Both C2 and C0 correlated with blood urea (r = -0.18, P = 0.0001; r = -0.12, P = 0.0002) and creatinine (r = -0.19, P = 0.0004; r = -0.19, P = 0.0001 respectively). By logistic regression higher C2 (>740) was associated with higher total severe rejection score at 2 years (P = 0.006). C2 showed better correlation with CsA dose, renal function, rejection profile and less variability between patients than C0. C2 may improve CsA-based immunosuppression in HT.