Celik S, Doesch A O, Konstandin M H, Kristen A V, Ammon K, Sack F-U, Schnabel P, Katus H A, Dengler T J
Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
Transplant Proc. 2011 Jun;43(5):1862-7. doi: 10.1016/j.transproceed.2010.12.059.
Calcineurin inhibitor (CNI)-free immunosuppression is used increasingly after heart transplantation to avoid CNI toxicity, but in the absence of a randomized trial, concerns remain over an increased rejection risk.
We studied the incidence of graft rejection episodes among all cardiac graft recipients, beginning with the first introduction of CNI-free protocols. We compared events during CNI-free and CNI-containing immunosuppression among 231 transplant recipients of overall mean age 55.2 ± 11.8 years, from a mean 5.2 ± 5.4 years after transplantation through a mean follow-up of 3.1 ± 1.4 years. We considered as acute rejection episodes requiring treatment those of International Society for Heart and Lung Transplantation.
During the total follow-up of 685 patient years (CNI-containing, 563; CNI-free, 122), we performed 1,374 biopsies which diagnosed 78 rejection episodes. More biopsies were performed in CNI-free patients: biopsies/patient-month of CNI-containing, 0.13 versus CNI-free, 0.22 (P < .05). The incidence of rejection episodes per patient-month was significantly higher on CNI-free compared with CNI therapy, among patients switched both early and later after heart transplantation, namely, within 1 year, 0.119 versus 0.035 (P = .02); beyond 1 year, 0.011 versus 0.004 (P = .007); beyond 2 years, 0.007 versus 0.003 (P = .04); and beyond 5 years: 0.00578 versus 0.00173 (P = .04).
Rejection incidence during CNI-free immunosuppression protocols after heart transplantation was significantly increased in both early and later postoperative periods. Given the potentially long delay to rejection occurrence, patients should be monitored closely for several months after a switch to CNI-free immunosuppressive protocols.
心脏移植后，为避免钙调神经磷酸酶抑制剂（CNI）毒性，越来越多地采用无CNI免疫抑制方案，但在缺乏随机试验的情况下，人们仍担心排斥反应风险会增加。
我们研究了所有心脏移植受者中移植排斥反应发作的发生率，从首次引入无CNI方案开始。我们比较了231例平均年龄为55.2±11.8岁的移植受者在无CNI和含CNI免疫抑制期间的事件，这些受者在移植后平均5.2±5.4年，平均随访3.1±1.4年。我们将国际心肺移植学会认定的需要治疗的急性排斥反应发作视为急性排斥反应发作。
在685患者年的总随访期间（含CNI，563；无CNI，122），我们进行了1374次活检，诊断出78次排斥反应发作。无CNI患者进行的活检更多：含CNI患者每月每例活检次数为0.13，无CNI患者为0.22（P<.05）。在心脏移植后早期和晚期转换的患者中，即1年内、0.119对0.035（P=.02）；1年后、0.011对0.004（P=.007）；2年后、0.007对0.003（P=.04）；5年后：0.00578对0.00173（P=.04），无CNI时每患者月排斥反应发作的发生率显著高于CNI治疗。
心脏移植后无CNI免疫抑制方案期间，术后早期和晚期排斥反应发生率均显著增加。鉴于排斥反应发生可能有较长延迟，在转换为无CNI免疫抑制方案后，应密切监测患者数月。
