Follow-up biopsies with microvascular inflammation and persistent donor specific antibodies identify ongoing rejection in pediatric kidney transplant recipients.

IF 2.6 3区 医学 Q1 PEDIATRICS
Clarkson Crane, Janara Mehrabli, Natalie Ellington, Katayoon Shayan, Gerald P Morris, Elizbeth Ingulli
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引用次数: 0

Abstract

Background: Inadequate treatment of acute rejection (AR) in pediatric kidney transplant recipients (KTR) can contribute to early allograft failure. Serum creatinine is an insensitive marker of allograft function, especially in the pediatric population, and may not detect ongoing rejection after treatment. We evaluated the utility of follow-up biopsies to detect persistent inflammation and future episodes of rejection.

Methods: We performed a single-center retrospective review to identify pediatric KTR with biopsy-proven rejection and a subsequent follow-up biopsy, noting type of AR, Banff scores, serum creatinine, and presence of donor specific antibodies (DSA). Outcomes included resolution of AR, change in eGFR, DSA, persistent microvascular inflammation (MVI) and future episodes of AR.

Results: Twelve cases of cellular (TCMR), 9 antibody-mediated (AMR), and 8 mixed cases of AR were identified among 23 KTR. Resolution was noted in 75% with TCMR, significantly higher than AMR (22%) or mixed rejection (13%), p < 0.01. Those without resolution of AR on follow-up biopsy were more likely to have ongoing episodes of AR or graft loss (p = 0.02). Persistence of DSA and MVI was associated with lack of AR resolution (p = 0.01 and p = 0.001, respectively). Those with persistent MVI on follow-up biopsy had higher probability of future AR events or graft loss, p = 0.003.

Conclusion: Follow-up biopsies to assess response to AR treatment revealed that most cases of TCMR were successfully treated but that AMR and mixed rejection portend a component of chronicity and more complicated course. Identification of persistent subclinical inflammation predicts future rejection episodes, has adverse effects on graft longevity, and can inform the need for additional treatment. We advocate for implementation of a follow-up biopsy protocol and future study of non-invasive biomarkers paired with protocol biopsies.

随访活检发现微血管炎症和持续存在的捐献者特异性抗体,可确定小儿肾移植受者的排斥反应仍在持续。
背景:小儿肾移植受者(KTR)急性排斥反应(AR)治疗不当会导致早期异体移植失败。血清肌酐是异体移植功能的不敏感标志物,尤其是在儿科人群中,而且可能无法检测出治疗后的持续排斥反应。我们评估了随访活检在检测持续炎症和未来排斥反应发作方面的作用:我们进行了一项单中心回顾性研究,以确定有活检证实的排斥反应和后续随访活检的小儿 KTR,并记录 AR 类型、Banff 评分、血清肌酐和是否存在供体特异性抗体 (DSA)。结果包括AR的缓解、eGFR的变化、DSA、持续性微血管炎症(MVI)和未来的AR发作:结果:在 23 例 KTR 中发现了 12 例细胞性 AR(TCMR)、9 例抗体介导型 AR(AMR)和 8 例混合型 AR。75%的TCMR患者病情得到缓解,明显高于AMR(22%)或混合排斥反应(13%):评估 AR 治疗反应的随访活组织检查显示,大多数 TCMR 病例都得到了成功治疗,但 AMR 和混合排斥反应则预示着慢性化和更复杂的病程。发现持续的亚临床炎症可预测未来的排斥反应,对移植物的寿命有不利影响,并可告知是否需要额外治疗。我们主张实施随访活检方案,并在未来研究与活检方案相配合的非侵入性生物标志物。
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来源期刊
Pediatric Nephrology
Pediatric Nephrology 医学-泌尿学与肾脏学
CiteScore
4.70
自引率
20.00%
发文量
465
审稿时长
1 months
期刊介绍: International Pediatric Nephrology Association Pediatric Nephrology publishes original clinical research related to acute and chronic diseases that affect renal function, blood pressure, and fluid and electrolyte disorders in children. Studies may involve medical, surgical, nutritional, physiologic, biochemical, genetic, pathologic or immunologic aspects of disease, imaging techniques or consequences of acute or chronic kidney disease. There are 12 issues per year that contain Editorial Commentaries, Reviews, Educational Reviews, Original Articles, Brief Reports, Rapid Communications, Clinical Quizzes, and Letters to the Editors.
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