Early Immunosuppressive Exposure of Enteric-Coated-Mycophenolate Sodium Plus Tacrolimus Associated with Acute Rejection in Expanded Criteria Donor Kidney Transplantation

Background: Immunosuppressive agents are still inefficient in preventing biopsy-proven acute rejection (BPAR) after expanded criteria donor (ECD) kidney transplantation. The aim of this study was to investigate the relationships between early immunosuppressive exposure and the development of BPAR. Methods: We performed a retrospective study of 58 recipients of ECD kidney transplantation treated with enteric-coated-mycophenolate sodium, tacrolimus (Tac), and prednisone. The levels of mycophenolic acid-area under the curve (MPA-AUC)_0-12h and Tac C₀were measured at the 1^st week and the 1^st month posttransplant, respectively. The correlation was assessed by multivariate logistic regression. Results: The occurrence rates of BPAR and antibody-mediated rejection were 24.1% and 10.3%, respectively. A low level of MPA-AUC_0-12hat the 1^st week posttransplant was found in BPAR recipients (38.42 ± 8.37 vs. 50.64 ± 13.22, P < 0.01). In addition, the incidence of BPAR was significantly high (P < 0.05) when the MPA-AUC_0-12hlevel was <30 mg·h^-1·L^-1 at the 1^st week (15.0% vs. 44.4%) or the Tac C₀was <4 ng/ml at the 1^st month posttransplant (33.3% vs. 21.6%). Multivariable logistic regression analysis showed that the MPA-AUC_0-12hat the 1^st week (OR: 0.842, 95% CI: 0.784-0.903) and the Tac C₀at the 1^st month (OR: 0.904, 95% CI: 0.822-0.986) had significant inverse correlation with BPAR (P < 0.05). Conclusions: Low-level exposure of MPA and Tac C₀in the early weeks posttransplant reflects an increased acute rejection risk, which suggested that MPA-AUC_0-12h <30 mg·h^-1·L^-1 and Tac C₀ <4 ng/ml should be avoided in the first few weeks after transplantation.