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 1st week and the 1st 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-AUC0-12h at the 1st 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-AUC0-12hlevel was <30 mg·h-1·L-1 at the 1st week (15.0% vs. 44.4%) or the Tac C0was <4 ng/ml at the 1st month posttransplant (33.3% vs. 21.6%). Multivariable logistic regression analysis showed that the MPA-AUC0-12h at the 1st week (OR: 0.842, 95% CI: 0.784-0.903) and the Tac C0at the 1st 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-AUC0-12h <30 mg·h-1·L-1 and Tac C0 <4 ng/ml should be avoided in the first few weeks after transplantation.
扩大标准的供肾肾移植术后早期免疫抑制剂暴露与急性排斥反应的相关性研究摘要背景：在扩大标准的供体（expanded criteria donor, ECD）肾移植术后如何有效的应用免疫抑制剂预防活检证实的急性排斥反应（biopsy-proven acute rejection, BPAR）仍然存在争议。因此，本研究的目的是探讨早期免疫抑制剂暴露与BPAR发生之间的关系，以期为肾移植术后早期免疫抑制剂的应用提供依据。 方法：我们回顾性分析了58例ECD肾移植受体早期免疫抑制剂暴露与BPAR的相关性，58例受体的免疫抑制剂方案为麦考酚钠肠溶片（enteric-coated mycophenolate sodium, EC-MPS）、他克莫司（tacrolimus, Tac）和强的松（prednisone, pred）。MPA-AUC 0-12h 和 Tac C0分别在术后1周和1月应用酶联免疫法进行检测。并采用多元logistic回归分析评估其与BPAR的相关性。 结果：BPAR和抗体介导排斥反应（antibody-mediated rejection, AMR）的发生率分别为24.1%和10.3%。术后1周发生BPAR的受体MPA-AUC 0-12h水平显著低于未发生BPAR的受体（p<0.01）。并且，在术后1周受体MPA-AUC 0-12h水平小于30mg·h-1∙L-1或术后1月受体Tac C0 水平小于4 ng/ml时BPAR发生率显著增加（p<0.05）。多因素Logistic回归分析显示，在术后1周时受体MPA-AUC 0-12h和术后1月受体Tac C0与BPAR呈负相关性（p<0.05）。 结论：肾移植术后早期免疫抑制剂MPA-AUC 0-12h 和 Tac C0低暴露增加BPAR的风险。在肾移植术后早期应避免MPA-AUC 0-12h水平小于30mg h/L和Tac C0 水平小于4 ng/ml。.
Keywords: Acute Rejection; Enteric-Coated-Mycophenolate Sodium; Expanded Criteria Donor; Kidney Transplantation; Tacrolimus.