Chronic antibody-mediated rejection, caused by de novo donor-specific antibody (dnDSA) production, results in poor graft survival. To prevent dnDSA production, optimal blood levels of immunosuppressive drugs in living donor kidney transplant recipients were determined. A total of 772 recipients underwent living donor kidney transplantation between January 2008 and December 2017. Graft survival and risk factors for dnDSA production were investigated in 647 recipients. Optimal blood levels of tacrolimus (TAC) and extended-release TAC (TACER) were measured in recipients receiving steroids and mycophenolate mofetil, combined with TAC (n = 53) or TACER (n = 135). Receiver operating characteristic (ROC) curve analysis and comparisons between dnDSA-negative and dnDSA-positive recipients were carried out. The Kaplan-Meier method revealed significantly poor graft survival in dnDSA-positive recipients (P < 0.001). Cox regression models indicated calcineurin inhibitor withdrawal as a significant risk for dnDSA production (P < 0.001; hazard ratio 6.637; 95% confidence interval 2.667–6.517). Average trough levels of TAC and TACER in dnDSA-negative recipients were significantly higher than those in dnDSA-positive recipients (4.88 vs 3.69 ng TAC/ml, P = 0.023, and 4.60 vs 3.85 ng TACER/ml, P = 0.001). ROC curve analysis indicated 4.325 and 3.990 ng/ml as the best trough levels under TAC- and TACER-based regimens, respectively, to prevent dnDSA production (areas under the curve: 0.788 and 0.813, respectively). Maintenance of the trough levels of TAC > 4.325 ng/ml and TACER > 3.990 ng/ml may prevent dnDSA production.

从头引起的慢性抗体介导的排斥反应供体特异性抗体（dnDSA）的产生会导致移植物存活率降低。为了防止dnDSA的产生，确定了活体供体肾移植受者的最佳免疫抑制药物血药浓度。在2008年1月至2017年12月之间，共有772名接受活体供肾的接受者进行了移植。对647位接受者进行了移植存活和dnDSA产生的危险因素的调查。在接受类固醇和霉酚酸酯联合TAC（n = 53）或TACER（n = 135）的接受者中，测量了他克莫司（TAC）和缓释TAC（TACER）的最佳血药浓度。进行了接收者工作特征（ROC）曲线分析，并对dnDSA阴性和dnDSA阳性接受者进行了比较。Kaplan-Meier方法显示dnDSA阳性受体的移植物存活率显着降低（P  <0.001）。Cox回归模型表明，钙调神经磷酸酶抑制剂的退出是dnDSA产生的重大风险（P  <0.001；危险比6.637； 95％置信区间2.667–6.517）。dnDSA阴性接受者的TAC和TACER的平均谷值显着高于dnDSA阳性接受者的平均谷值（4.88 vs.3.69 ng TAC / ml，P  = 0.023，4.60 vs 3.85 ng TACER / ml，P  = 0.001）。ROC曲线分析表明，在基于TAC和TACER的方案下，最佳谷底水平分别为4.325和3.990 ng / ml，以防止dnDSA产生（曲线下的面积分别为0.788和0.813）。维持TAC的谷值> 4.325 ng / ml和TACER> 3.990 ng / ml可能会阻止dnDSA的产生。