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肾移植后阿仑单抗诱导治疗与肾小球疾病复发

Alemtuzumab induction and recurrence of glomerular disease after kidney transplantation.

作者信息

Pascual Julio, Mezrich Joshua D, Djamali Arjang, Leverson Glen, Chin L Thomas, Torrealba José, Bloom Debra, Voss Barbara, Becker Bryan N, Knechtle Stuart J, Sollinger Hans W, Pirsch John D, Samaniego Milagros D

机构信息

Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI 53713, USA.

出版信息

Transplantation. 2007 Jun 15;83(11):1429-34. doi: 10.1097/01.tp.0000264554.39645.74.

Abstract

BACKGROUND

An increase in the incidence of autoimmune diseases has been described in patients receiving alemtuzumab.

METHODS

To determine whether induction with alemtuzumab increases recurrence of glomerular disease, we performed a retrospective study in 443 patients with biopsy-proven glomerular diseases undergoing kidney transplantation. Patients receiving alemtuzumab (n=161) were compared with those receiving interleukin (IL)-2-receptor antagonists (n=217) or antithymocyte globulin (n=64).

RESULTS

Biopsy-proven glomerular disease recurrence was similar in patients induced with alemtuzumab or IL-2 receptor antagonists. Patients receiving antithymocyte antibody had a lower recurrence rate than patients treated with other induction agents, with borderline significance (hazard ratio [HR] 0.13, 95% confidence interval [95% CI] 0.02-0.98, P=0.047). Patients with systemic lupus treated with alemtuzumab had a similar re-emergence of autoreactive antibodies to patients treated with other agents. Recurrent disease increased the risk of allograft failure (HR 2.36, 95% CI 1.28-4.32, P=0.0056). The development of acute rejection and the use of deceased (vs. living) donor kidneys were also significant factors influencing graft survival. A greater risk of mortality was detected in those patients with recurrent glomerular disease (HR 3.76, 95% CI 1.37-10.35, P=0.01), whereas increased age at transplantation (HR 1.05) and the use of deceased (vs. living) donor kidneys (HR 3.20) also increased mortality. No specific induction agent significantly affected graft loss or mortality when using adjusted or unadjusted hazard ratios.

CONCLUSIONS

In this retrospective analysis, induction with alemtuzumab did not increase the rate of re-emergence of autoantibodies or biopsy-proven recurrence of glomerular disease. A slight reduction in the incidence of recurrence was observed in patients treated with thymoglobulin, yet this observation can only be validated in a prospective randomized trial.

摘要

背景

接受阿仑单抗治疗的患者中自身免疫性疾病发病率有所增加。

方法

为确定阿仑单抗诱导治疗是否会增加肾小球疾病的复发率,我们对443例经活检证实患有肾小球疾病且正在接受肾移植的患者进行了一项回顾性研究。将接受阿仑单抗治疗的患者(n = 161)与接受白细胞介素(IL)-2受体拮抗剂治疗的患者(n = 217)或抗胸腺细胞球蛋白治疗的患者(n = 64)进行比较。

结果

经活检证实,接受阿仑单抗或IL-2受体拮抗剂诱导治疗的患者肾小球疾病复发情况相似。接受抗胸腺细胞抗体治疗的患者复发率低于接受其他诱导治疗的患者,差异具有临界显著性(风险比[HR] 0.13,95%置信区间[95%CI] 0.02 - 0.98,P = 0.047)。接受阿仑单抗治疗的系统性红斑狼疮患者自身反应性抗体的再次出现情况与接受其他药物治疗的患者相似。复发性疾病增加了移植肾失功的风险(HR 2.36,95%CI 1.28 - 4.32,P = 0.0056)。急性排斥反应的发生以及使用 deceased(与 living 相对)供体肾也是影响移植肾存活的重要因素。复发性肾小球疾病患者的死亡风险更高(HR 3.76,95%CI 1.37 - 10.35,P = 0.01),而移植时年龄增加(HR 1.05)以及使用 deceased(与 living 相对)供体肾(HR 3.20)也会增加死亡率。使用调整或未调整的风险比时,没有特定的诱导药物对移植肾丢失或死亡率有显著影响。

结论

在这项回顾性分析中,阿仑单抗诱导治疗并未增加自身抗体的再次出现率或经活检证实的肾小球疾病复发率。使用胸腺球蛋白治疗的患者复发率略有降低,但这一观察结果仅在前瞻性随机试验中得到验证。

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