Outcomes of paediatric kidney transplant recipients using the updated 2013/2017 Banff histopathological classification for antibody-mediated rejection

Preka, Evgenia; Sekar, Thivya; Garcia, Sergio Camilo Lopez; Shaw, Olivia; Kessaris, Nicos; Mamode, Nizam; Stojanović, Jelena; Sebire, Neil J.; Kim, Jon Jin; Marks, Stephen D.

doi:10.1007/s00467-021-05103-x

Cited by 3 publications

(1 citation statement)

References 26 publications

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“…Secondly, Banff diagnostic criteria and categories are adjusted based on antecedent literature, and as they arise as a synthesis of several different studies, rarely fully align with literature on which they are based. Conversely, outcomes of AMR diagnoses according to their strict definitions in the Banff Classification have rarely been investigated for either their association with outcome, or their success in delineating which patients are eligible for a specific therapy; where this has been done, results show improved prediction of outcome with the 2013 version compared to the 2003/2007 Classification, and with the 2013 version compared to the 2017 Classification ( 25 , 26 ). Instead, researchers often use slightly different definitions for the categories, with bespoke combinations of components and cut-offs for defining AMR, instead of the strict definitions last proposed by Banff.…”

Section: Amr and Allograft Outcomementioning

confidence: 99%

Proposed Definitions of Antibody-Mediated Rejection for Use as a Clinical Trial Endpoint in Kidney Transplantation

Roufosse

Becker

Rabant³

et al. 2022

Transpl Int

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Antibody-mediated rejection (AMR) is caused by antibodies that recognize donor human leukocyte antigen (HLA) or other targets. As knowledge of AMR pathophysiology has increased, a combination of factors is necessary to confirm the diagnosis and phenotype. However, frequent modifications to the AMR definition have made it difficult to compare data and evaluate associations between AMR and graft outcome. The present paper was developed following a Broad Scientific Advice request from the European Society for Organ Transplantation (ESOT) to the European Medicines Agency (EMA), which explored whether updating guidelines on clinical trial endpoints would encourage innovations in kidney transplantation research. ESOT considers that an AMR diagnosis must be based on a combination of histopathological factors and presence of donor-specific HLA antibodies in the recipient. Evidence for associations between individual features of AMR and impaired graft outcome is noted for microvascular inflammation scores ≥2 and glomerular basement membrane splitting of >10% of the entire tuft in the most severely affected glomerulus. Together, these should form the basis for AMR-related endpoints in clinical trials of kidney transplantation, although modifications and restrictions to the Banff diagnostic definition of AMR are proposed for this purpose. The EMA provided recommendations based on this Broad Scientific Advice request in December 2020; further discussion, and consensus on the restricted definition of the AMR endpoint, is required.

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Section: Amr and Allograft Outcomementioning

confidence: 99%

Proposed Definitions of Antibody-Mediated Rejection for Use as a Clinical Trial Endpoint in Kidney Transplantation

Roufosse

Becker

Rabant³

et al. 2022

Transpl Int

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How to Manage Children with Chronic Kidney Allograft Dysfunction

Garcia-Nicoletti

Baker

Marks

2023

Pediatric Solid Organ Transplantation

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miR-155 Derived from Bone Marrow Mesenchymal Stem Cell-Secreted Exosomes Reduces Kidney Rejection in Rat Allogeneic Transplantation Model via SDF-1/CXCR4

Hong-mei

Quan

Xiao

et al. 2022

j biomater tissue eng

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Aberrantly expressed miR-155 is associated with renal rejection after allogeneic transplantation. This study mainly explored the mechanism of miR-155 derived from bone marrow mesenchymal stem cell-secreted exosomes (BMSC-exo) in renal rejection after allogeneic transplantation. Thirty Fischer rats and 40 Lewis rats were used as donors and recipients, respectively. The Lewis rats were randomized into 4 groups (10 rats per group): Control group, miR-155 group, positive control group and CXCR4 agonist group. The following indicators were monitored in BMSC-exo: miR-155 expression, serum creatinine level, renal histopathological changes, CADI score, number of cells that were positive for TGF-β, Smad3 and α-SMA, as well as the protein levels of Smad3, TGF-β, CXCR4 and SDF-1. miR-155 expression in BMSC-exo was significantly higher than that in HKb-20 cells. On the 7th day after surgery, the serum creatinine levels of rats in the miR-155 group and positive control group reduced significantly, while decreasing slowly in the control group and CXCR4 agonist group. The CADI scores of rats in the miR-155 group and positive control group were significantly higher than those in the control group and CXCR4 agonist group (P < 0.05). No significant difference was found either between the miR-155 group and positive control group, or between the control group and CXCR4 agonist group (P > 0.05). Rats in the control group and CXCR4 agonist group had more cells that were positive for TGF-β, Smad3 and α-SMA, while those in the miR-155 group and positive control group showed less. The Smad3, TGF-β, CXCR4 and SDF-1 proteins were weakly expressed in the miR-155 group and positive control group, but strongly expressed in the control group and CXCR4 agonist group. No significant difference in the protein levels was found either between the miR-155 group and positive control group, or between the control group and CXCR4 agonist group (P > 0.05). miR-155 derived from BMSC-exo is protective against allogeneic kidney transplantation. Specifically, BMSC-exo-derived miR-155 blocked the activity of SDF-1/CXCR4 and TGF-β/Smad3 pathways, thereby downregulating the expression of α-SMA. As a result, it ameliorated renal fibrosis and alleviated renal dysfunction, ultimately leading to the prevention and reduction of renal rejection following allograft transplantation.

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Outcomes of paediatric kidney transplant recipients using the updated 2013/2017 Banff histopathological classification for antibody-mediated rejection

Cited by 3 publications

References 26 publications

Proposed Definitions of Antibody-Mediated Rejection for Use as a Clinical Trial Endpoint in Kidney Transplantation

Proposed Definitions of Antibody-Mediated Rejection for Use as a Clinical Trial Endpoint in Kidney Transplantation

How to Manage Children with Chronic Kidney Allograft Dysfunction

miR-155 Derived from Bone Marrow Mesenchymal Stem Cell-Secreted Exosomes Reduces Kidney Rejection in Rat Allogeneic Transplantation Model via SDF-1/CXCR4

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