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. 2025 Jul;40(7):2375-2382.
doi: 10.1007/s00467-025-06671-y. Epub 2025 Jan 28.

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

Clarkson Crane  1 , Janara Mehrabli  2 , Natalie Ellington  3 , Katayoon Shayan  3 , Gerald P Morris  3 , Elizbeth Ingulli  4
Affiliations

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

Clarkson Crane et al. Pediatr Nephrol. 2025 Jul.

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.

Keywords: Acute rejection; Kidney transplant; Pediatric; Protocol biopsy.

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Conflict of interest statement

Declarations. Ethics approval: The Retrospective and Prospective Kidney Transplant Database is approved by the Institutional Review Board of the University of California San Diego and Rady Children’s Hospital. Need for consent and publication was waived due to minimal risk to participants. Competing interest: The authors declare no competing interests.

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