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在医学复杂性肾移植受者中,早期或晚期移植物功能障碍时,联合使用低剂量他克莫司维持治疗,使用贝拉西普进行抢救后预防急性排斥反应。

Prevention of acute rejection after rescue with Belatacept by association of low-dose Tacrolimus maintenance in medically complex kidney transplant recipients with early or late graft dysfunction.

机构信息

Renal Transplant Center "A. Vercellone", Nephrology, Department of Medical Sciences, Dialysis and Renal Transplant Division, "Città della Salute e della Scienza" Hospital, University of Turin, Turin, Italy.

Department of Medical Sciences, Division of Pathology, "Città della Salute e della Scienza" Hospital, University of Turin, Turin, Italy.

出版信息

PLoS One. 2020 Oct 15;15(10):e0240335. doi: 10.1371/journal.pone.0240335. eCollection 2020.

Abstract

BACKGROUND

Increased acute rejection risk in rescue protocols with Belatacept may limit its use particularly in medically complex patients where preexisting increased risk of rejection couples with CNI toxicity.

METHODS

Retrospective analysis was performed in 19 KTs shifted to a Belatacept-based immunosuppression with low-dose Tacrolimus (2-3 ng/mL) after evidence of allograft disfunction, including patients with primary non-function (PNF), chronic-active antibody-mediated rejection (cAMR), history of previous KTs and/or other concomitant transplants (liver, pancreas). Evaluation of CD28+ CD4+ effector memory T cell (TEM) before conversion was performed in 10/19.

RESULTS

Kidney function significantly improved (median eGFR 16.5 ml/min/1.73m2 before vs 25 ml/min after; p = 0.001) at a median time after conversion of 12.5 months (9.1-17.8). Overall graft and patient survival were 89.5% and 100% respectively. Definitive weaning from dialysis in 5/5 KTs with PNF was observed, whereas 7/8 patients lost their graft within first year in a control group. eGFR significantly ameliorated in re-trasplants (p = 0.001) and stabilized in KTs with other organ transplants or cAMR. No acute rejection episodes occurred, despite the significant risk suggested by high frequency of CD28+ CD4+ TEM in most patients. Opportunistic infections were limited and most common in early vs late-converted.

CONCLUSIONS

Rescue association of Belatacept with low-dose Tacrolimus in medically complex KTs is a feasible option that allows prevention of acute rejection and amelioration of graft function.

摘要

背景

贝伐珠单抗在抢救方案中急性排斥反应风险增加,可能会限制其使用,特别是在有预先存在的排斥反应风险且合并有钙调磷酸酶抑制剂毒性的医学复杂患者中。

方法

对 19 例因移植物功能障碍(包括原发性无功能、慢性活动性抗体介导的排斥反应、既往接受过肾移植和/或其他器官移植[肝、胰腺])而转换为以贝利尤单抗为基础、联合低剂量他克莫司(2-3ng/ml)的免疫抑制剂的患者进行回顾性分析。在转换前对 10/19 例患者进行了 CD28+CD4+效应记忆 T 细胞(TEM)检测。

结果

在转换后的中位数 12.5 个月(9.1-17.8)时,患者的肾功能明显改善(转换前中位数 eGFR 为 16.5ml/min/1.73m2,转换后为 25ml/min;p=0.001)。总的移植物和患者存活率分别为 89.5%和 100%。在原发性无功能的 5 例患者中,5 例均成功摆脱透析,而在对照组中,8 例患者中有 7 例在第 1 年内失功。再次移植的 eGFR 显著改善(p=0.001),在合并其他器官移植或慢性抗体介导排斥反应的患者中则保持稳定。尽管大多数患者的 CD28+CD4+TEM 频率较高,提示存在较高的急性排斥反应风险,但未发生急性排斥反应。机会性感染有限,且在早期转换组比晚期转换组更为常见。

结论

在医学复杂肾移植患者中,贝利尤单抗联合低剂量他克莫司抢救治疗是一种可行的选择,可预防急性排斥反应并改善移植物功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1029/7561183/4b2fe71855a2/pone.0240335.g001.jpg

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