肾移植术后早发型与迟发型抗体介导排斥反应的预后分析与治疗选择

Comparison of treatments and outcomes between early and late antibody-mediated rejection after kidney transplantation

目的探讨肾移植术后早发型和迟发型抗体介导的排斥反应(antibody-mediated rejection,AMR)的治疗选择和预后。方法回顾2013年1月至2022年12月于中山大学附属第一医院行移植肾穿刺活检并依据Banff 2019标准诊断为AMR的141例受者的临床资料。根据AMR的诊断时间在术后30 d内和30 d后将其分为早发型AMR(早发型AMR组,19例)和迟发型AMR(迟发型AMR组,122例)。主要研究结局为受者和死亡删失移植肾存活率、随访估算的肾小球滤过率(estimated glomerular filtration rate,eGFR)和免疫优势供体特异性抗体强度变化。使用Wilcoxon检验评估eGFR和供体特异性抗体强度差异,Kaplan-Meier曲线和log-rank检验进行生存分析,并对受者的AMR治疗方案进行分类。结果141例受者的中位随访时间为2.6(1.2,5.2)年。早发型AMR组未见移植肾失功;迟发型AMR组有44例受者发生移植肾失功,其中因为AMR进展导致移植肾失功者34例(77.2%)。早发型AMR组受者的5年死亡删失移植肾存活率好于出现迟发型AMR受者[100%比60.1%(50.5%,71.6%),P=0.002]。早发型AMR组受者治疗后1年eGFR变化值明显优于迟发型AMR组[19.3(-2.6,38.1)比-3.3(-14.0,5.4),P=0.001]。早发型AMR组受者随访1年时的平均荧光强度为1158(401.5,3126.5),明显低于诊断时的3120.5(2392.8,9340.0)和迟发型AMR的8094(2251.5,13560.5),差异均有统计学意义(P=0.005和P<0.001)。早发型AMR组治疗采用标准方案者3例(15.8%),以利妥昔单抗和/或硼替佐米为核心的其他方案者7例(43.8%)。迟发型AMR组治疗采用标准方案者16例(13.1%),加强方案者9例(7.4%),利妥昔单抗和/或硼替佐米为核心的其他治疗方案者32例(26.2%),单用MP者21例(17.2%)。结论本研究中早发型AMR组的预后优于迟发型AMR组。对于早发型AMR,建议早期采用较强的免疫抑制方案;对于迟发型AMR,要尽早发现、及时治疗,其治疗方案也需要进行个体化选择。

ObjectiveTo explore the impact of early and late antibody-mediated rejection(AMR)on treatment options and allograft outcomes after kidney transplantation(KT).MethodsFrom January 2013 to December 2022,the study retrospectively enrolled 141 KT allograft recipients receiving allograft biopsy and diagnosed as AMR according to the Banff 2019 criteria.Recipients with a diagnosis of AMR within 30 days post-KT were classified into early AMR group(n=19)while the remainders assigned as late AMR group(n=122).The outcome endpoints included recipient survival rate,death-censored graft survival rate,follow-up estimated glomerular filtration rate(eGFR)and immunodominant donor-specific antibody(DSA)intensity.Wilcoxon's test was utilized for assessing the differences in eGFR and DSA intensity while Kaplan-Meier curve and Log-rank test were employed for evaluating graft survival impact.Treatment regimens for AMR were collected and categorized.ResultsThe median follow-up duration was 2.6(1.2,5.2)year.No graft failure was noted in early AMR group while 44 recipients in late AMR group experienced graft failure,with 34 cases(77.2%)due to AMR progression.The 5-year death-censored graft survival rate was significantly better in early AMR group than that in late AMR group[100%vs 60.1%(50.5%,71.6%),P=0.002].The one-year change in eGFR for early AMR group was significantly superior to that of late AMR group[19.3(-2.6,38.1)vs-3.3(-14.0,5.4),P=0.001].One-year mean fluorescent intensity(MFI)of early AMR group was 1158(401.5,3126.5).It was significantly lower than that when diagnosed with early AMR[3120.5(2392.8,9340.0)]and one-year MFI of late AMR group[8094(2251.5,13560.5)](P=0.005,P<0.001).Early AMR group primarily received standard treatment(3/19,15.8%)and regimens centered on rituximab and/or bortezomib(7/19,43.8%).Late AMR group mainly received standard(16/122,13.1%)or intensified regimens(9/122,7.4%)and regimens focused upon rituximab and/or bortezomib(32/122,26.2%)and MP monotherapy(21/122,17.2%).ConclusionThe outcome for early AMR is significantly better than that for late AMR.For early AMR,early and robust immunosuppression is recommended.For late AMR,early detection and timely treatment are crucial and individualized strategies should be implemented.