Challenges of calcineurin inhibitor withdrawal following combined pancreas and kidney transplantation: Results of a prospective, randomized clinical trial.
Challenges of calcineurin inhibitor withdrawal following combined pancreas and kidney transplantation: Results of a prospective, randomized clinical trial.
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DOI：
10.1111/ajt.15817
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发表时间：
2020-06
期刊：
影响因子：
--
通讯作者：
Newell KA
中科院分区：
文献类型：
--
作者：
Stock PG;Mannon RB;Armstrong B;Watson N;Ikle D;Robien MA;Morrison Y;Odorico J;Fridell J;Mehta AK;Newell KA
在美国国立卫生研究院（National Institutes of Health）申办的一项2期多中心开放标签随机试验中，将胰肾（SPK）联合移植受者随机分配至基于钙调神经磷酸酶抑制剂（CNI）的免疫抑制方案（他克莫司）（n=21）或使用低剂量CNI加共刺激阻断剂（贝拉西普）的研究组（n=22），并计划停用CNI。两组均采用兔ATG、霉酚酸钠或霉酚酸酯诱导治疗，并快速停用类固醇。在43/60例计划受试者入组后，停止入组和CNI退出。当时，两组胰腺活检证实的急性排斥反应（BPAR）发生率均较低，直到CNI停药，5例胰腺排斥反应中有4例发生在CNI停药期间或停药后。对照组（9.5%）和试验组（9.1%）的移植肾BPAR率均较低。52周时胰腺移植物存活率（定义为胰岛素非依赖性），对照组为21例（100%），研究组为19例（86%）。第52周时，两组的肾功能相似。贝拉西普的共刺激阻断不能提供足够的免疫抑制来可靠地预防接受CNI撤药的SPK移植中的胰腺排斥反应。
In a phase 2 multi-center open label randomized trial sponsored by the National Institutes of Health, simultaneous pancreas-kidney (SPK) recipients were randomized to a calcineurin inhibitor (CNI) based immunosuppressive regimen (tacrolimus) (n=21) or an investigational arm using low-dose CNI plus co-stimulation blockade (belatacept) with intended CNI withdrawal (n=22). Both arms included induction therapy with rabbit ATG, mycophenolate sodium or mycophenolate mofetil, and rapid withdrawal of steroids. Enrollment and CNI withdrawal were stopped after 43/60 planned subjects had been enrolled. At that time the rate of biopsy proven acute rejection (BPAR) of the pancreas was low in both groups until CNI was withdrawn, with four of the five pancreas rejections occurring during or after CNI withdrawal. The rate of BPAR of kidney allografts was low in both control (9.5%) and investigational (9.1%) arms. Pancreas graft survival at 52 weeks, defined by insulin independence, was 21 (100%) in the control group and 19 (86%) in the investigational arm. One subject in the investigational arm died with functioning pancreas and kidney grafts. Renal function at week 52 was similar in both arms. Costimulation blockade with belatacept did not provide sufficient immunosuppression to reliably prevent pancreas rejection in SPK transplants undergoing CNI withdrawal.
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抗Belatacept的排斥反应与CD28（+）内存CD8 T细胞有关。
DOI：
10.1111/ajt.14349
发表时间：
2017-09
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
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作者：
Mathews DV;Wakwe WC;Kim SC;Lowe MC;Breeden C;Roberts ME;Farris AB;Strobert EA;Jenkins JB;Larsen CP;Ford ML;Townsend R;Adams AB
通讯作者：
Adams AB
DOI：
10.1111/ajt.13613
发表时间：
2016-04
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
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作者：
Espinosa J;Herr F;Tharp G;Bosinger S;Song M;Farris AB 3rd;George R;Cheeseman J;Stempora L;Townsend R;Durrbach A;Kirk AD
通讯作者：
Kirk AD
影响因子：
158.5
作者：
Ekberg, Henrik;Tedesco-Silva, Helio;Halloran, Philip F.
通讯作者：
Halloran, Philip F.
影响因子：
6.2
作者：
Stratta, RJ;Alloway, RR;Hodge, E
通讯作者：
Hodge, E
DOI：
10.1038/nrneph.2016.9
发表时间：
2016-06
期刊：
Nature reviews. Nephrology
影响因子：
--
作者：
Espinosa JR;Samy KP;Kirk AD
通讯作者：
Kirk AD