Crane Clarkson, Mehrabli Janara, Ellington Natalie, Shayan Katayoon, Morris Gerald P, Ingulli Elizbeth
Department of Pediatrics, University of California San Diego, 3020 Children's Way MC 5137, San Diego, CA, 92123, USA.
Department of Biological Sciences, University of California San Diego, San Diego, CA, USA.
Pediatr Nephrol. 2025 Jul;40(7):2375-2382. doi: 10.1007/s00467-025-06671-y. Epub 2025 Jan 28.
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.
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.
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.
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.
小儿肾移植受者（KTR）急性排斥反应（AR）治疗不充分可导致早期移植肾失功。血清肌酐是移植肾功能的不敏感标志物，尤其是在儿科人群中，治疗后可能无法检测到持续的排斥反应。我们评估了随访活检在检测持续性炎症和未来排斥反应发作方面的效用。
我们进行了一项单中心回顾性研究，以确定经活检证实有排斥反应且随后进行了随访活检的小儿KTR，记录AR类型、班夫评分、血清肌酐以及供体特异性抗体（DSA）的存在情况。结局包括AR的缓解、估算肾小球滤过率（eGFR）的变化、DSA、持续性微血管炎症（MVI）以及未来的AR发作。
在23例KTR中，鉴定出12例细胞性（TCMR）、9例抗体介导性（AMR）和8例混合性AR病例。TCMR的缓解率为75%，显著高于AMR（22%）或混合性排斥反应（13%），p<0.01。随访活检时AR未缓解的患者更有可能出现持续性AR发作或移植肾丢失（p=0.02）。DSA和MVI的持续存在与AR未缓解相关（分别为p=0.01和p=0.001）。随访活检时有持续性MVI的患者未来发生AR事件或移植肾丢失的可能性更高，p=0.003。
评估AR治疗反应的随访活检显示，大多数TCMR病例得到了成功治疗，但AMR和混合性排斥反应预示着病程具有慢性化成分且更为复杂。持续性亚临床炎症的识别可预测未来的排斥反应发作，对移植肾存活有不利影响，并可为是否需要额外治疗提供依据。我们主张实施随访活检方案，并对与方案活检相结合的非侵入性生物标志物进行未来研究。
