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致敏儿科患者肾移植术前的管理。

Management of sensitized pediatric patients prior to renal transplantation.

作者信息

Pirojsakul Kwanchai, Desai Dev, Lacelle Chantale, Seikaly Mouin G

机构信息

Children's Medical Center, Dallas, TX, USA.

Pediatric Nephrology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

出版信息

Pediatr Nephrol. 2016 Oct;31(10):1691-8. doi: 10.1007/s00467-015-3295-z. Epub 2016 Jan 22.

DOI:10.1007/s00467-015-3295-z
PMID:26801944
Abstract

BACKGROUND

Data on renal allograft outcome in sensitized children are scarce. We report the clinical courses of four children who received desensitization therapy prior to renal transplantation in our institution.

METHODS

Between 2009 and 2011, four pediatric patients with stage 5 chronic kidney disease received desensitization therapy due to: (1) positive donor-specific antibodies (DSA) and/or crossmatches with potential living donors, (2) more than three positive crossmatches with deceased donors or (3) high calculated panel-reactive antibody of >80 %. Desensitization with rituximab, intravenous immunoglobulin and bortezomib was performed in all patients. Induction therapy included combinations of plasmapheresis and/or alemtuzumab or anti-thymocyte globulin. Standard post-transplant medications included tacrolimus, mycophenolate mofetil and prednisolone.

RESULTS

Post-transplant screening revealed DSA in three patients. Biopsy showed no evidence of rejection at 1 month in two patients, one of whom developed chronic active antibody-mediated rejection 4.5 years later. One patient developed borderline acute cellular rejection at 1 month, but the serum creatinine level was stable and DSA disappeared without treatment 1 month later, with stable long-term allograft function at 3 years. Estimated or measured glomerular filtration rate of the patients ranged between 30 and 75 ml/min/1.73 m(2) after 1 to 4.5 years.

CONCLUSIONS

The four sensitized patients reported here who received desensitization therapy had successful renal transplants with a low risk of immediate post-transplant rejection. Overall, long-term allograft functions and complications from immunosuppression were encouraging.

摘要

背景

关于致敏儿童肾移植结果的数据很少。我们报告了在我们机构接受肾移植前脱敏治疗的4名儿童的临床病程。

方法

2009年至2011年期间,4例5期慢性肾病患儿因以下原因接受脱敏治疗:(1)供者特异性抗体(DSA)阳性和/或与潜在活体供者交叉配型阳性;(2)与已故供者交叉配型阳性超过3次;或(3)计算得出的群体反应性抗体(PRA)>80%。所有患者均接受了利妥昔单抗、静脉注射免疫球蛋白和硼替佐米的脱敏治疗。诱导治疗包括血浆置换和/或阿仑单抗或抗胸腺细胞球蛋白的联合应用。标准的移植后药物包括他克莫司、霉酚酸酯和泼尼松龙。

结果

移植后筛查发现3例患者有DSA。活检显示2例患者在1个月时无排斥反应证据,其中1例在4.5年后发生慢性活动性抗体介导的排斥反应。1例患者在1个月时发生临界性急性细胞排斥反应,但血清肌酐水平稳定,1个月后未经治疗DSA消失,3年时移植肾功能长期稳定。1至4.5年后,患者的估计或测量肾小球滤过率在30至75 ml/min/1.73 m²之间。

结论

本文报道的4例接受脱敏治疗的致敏患者肾移植成功,移植后立即排斥反应风险低。总体而言,移植肾功能长期良好,免疫抑制并发症情况令人鼓舞。

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本文引用的文献

1
Modern approaches to incompatible kidney transplantation.不相容肾移植的现代方法。
World J Nephrol. 2015 Jul 6;4(3):354-62. doi: 10.5527/wjn.v4.i3.354.
2
Kidney transplantation in highly sensitized patients.高致敏患者的肾移植。
Br Med Bull. 2015 Jun;114(1):113-25. doi: 10.1093/bmb/ldv013. Epub 2015 May 1.
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Bortezomib-based antibody reduction therapy: the first step to “true” desensitization?基于硼替佐米的抗体减少疗法:迈向“真正”脱敏的第一步?
回顾阿仑单抗的临床药代动力学和药效学及其在肾移植中的应用。
Clin Pharmacokinet. 2018 Feb;57(2):191-207. doi: 10.1007/s40262-017-0573-x.
4
Safety and Efficacy of Alemtuzumab Induction in Highly Sensitized Pediatric Renal Transplant Recipients.阿仑单抗诱导治疗在高敏儿科肾移植受者中的安全性和有效性。
Transplantation. 2017 Apr;101(4):883-889. doi: 10.1097/TP.0000000000001416.
Am J Transplant. 2015 Jan;15(1):10-12. doi: 10.1111/ajt.13048.
4
HLA desensitization with bortezomib in a highly sensitized pediatric patient.在一名高度致敏的儿科患者中使用硼替佐米进行HLA脱敏治疗。
Pediatr Transplant. 2014 Dec;18(8):E280-2. doi: 10.1111/petr.12347. Epub 2014 Sep 1.
5
A closer look at rituximab induction on HLA antibody rebound following HLA-incompatible kidney transplantation.深入研究利妥昔单抗诱导对HLA不相合肾移植后HLA抗体反弹的影响。
Kidney Int. 2015 Feb;87(2):409-16. doi: 10.1038/ki.2014.261. Epub 2014 Jul 23.
6
Efficacy of bortezomib for reducing donor-specific antibodies in children and adolescents on a steroid minimization regimen.硼替佐米在儿童和青少年中对采用最小化类固醇方案降低供体特异性抗体的疗效。
Pediatr Transplant. 2014 Aug;18(5):463-8. doi: 10.1111/petr.12274. Epub 2014 May 12.
7
Validation of the CKiD formulae to estimate GFR in children post renal transplant.用于评估肾移植术后儿童肾小球滤过率(GFR)的CKiD公式的验证
Pediatr Nephrol. 2014 Mar;29(3):445-51. doi: 10.1007/s00467-013-2660-z. Epub 2013 Nov 26.
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Acute antibody-mediated rejection in pediatric kidney transplants: a single center experience.小儿肾移植中的急性抗体介导排斥反应:单中心经验
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