A Novel Ex Vivo Normothermic Perfusion Model of Human Antibody Mediated Rejection
1Transplantation, Guy's and St Thomas Hospitals NHS Trust and King's College London, London, United Kingdom, 2Transplantation and CTL Laboratory, Guy's and St Thomas Hospitals NHS Trust and King's College London, London, United Kingdom, 3Haematology and Thrombosis, Guy's and St Thomas Hospitals NHS Trust, London, United Kingdom, 4Histopathology, Guy's and St Thomas Hospitals NHS Trust, London, United Kingdom, 5Haematology and Thrombosis, Guy's and St Thomas Hospitals NHS Trust and King's College London, London, United Kingdom, 6Interface Physics, University of Bristol, London, United Kingdom, 7Inflammation, Thrombosis and Repair and Transplantation, Guy's and St Thomas Hospitals NHS Trust and King's College London, London, United Kingdom
Meeting: 2019 American Transplant Congress
Abstract number: A15
Keywords: Endothelial activation, Renal thrombosis
Session Information
Session Name: Poster Session A: Acute Rejection
Session Type: Poster Session
Date: Saturday, June 1, 2019
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall C & D
*Purpose: Currently, no human experimental model of antibody-mediated rejection (AMR) exists, making the assessment of therapeutic interventions difficult hence the aim of our work is to establish the first human kidney model of AMR using ex-vivo normothermic perfusion (EVNP).
*Methods: We developed AMR models caused by HLA (HLAi) and ABO antibodies (ABOi). 9 discarded human kidneys were used (including 3 pairs). All kidneys underwent standard pre-experimental EVNP stabilization. For each experiment, we either injected FFP (source of complement/coagulation factors) & 6mg/ml of w6/32 anti-class 1 antibody (for HLAi) or (pre-tested) high blood group antibody-titre FFP alone (for ABOi). EVNP renal blood flow index (RBFi ml/min/100g), C3 desArge and prothrombin 1+2 levels were taken with tissue biopsies. Our endpoints were: haemodynamic change, thrombosis, biopsy proven complement fixation.
*Results: A total of: 3 HLAi, 4 controls and 2 ABOi experiments were performed. Between 30-45 minutes post-antibody injection, all HLAi and one high-titre ABOi kidney showed a catastrophic reduction in RBFi with perfusion time (Fig.1) (change in RBFi ranging from 0 to -122 ml/min/100g and 0 to -93.6 ml/min/100g for HLAi and ABOi kidneys, respectively) compared to controls. C3 desAge activation (% change from baseline) ranged from +32% to +180% (HLAi); +60% to +433 (controls); +80% to +127% (ABOi). PT 1+2 activation (% change from baseline) ranged from +423% to +862% (HLAi); +218% to +2759% (controls); +835% to +1578% (ABOi). All HLAi kidneys fixed C4d, but controls and ABOi kidneys did not. Microvascular thrombi were present in 2 kidneys (HLAI/ABOi).
*Conclusions: Our work suggests an experimentally-induced antibody effect in this human kidney model system utilizing EVNP. This clinically relevant, original model may have future implications for shifting the paradigm towards investigating localized therapeutic renal cyto-protection and experimental models of accommodation.
To cite this abstract in AMA style:
Chandak P, Phillips BL, Uwechue R, Callaghan CJ, Shaw O, Maggs T, Woodford L, Veniard D, Perera R, Parmar K, Hunt B, Bennett D, Kessaris N, Dorling A, Mamode N. A Novel Ex Vivo Normothermic Perfusion Model of Human Antibody Mediated Rejection [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/a-novel-ex-vivo-normothermic-perfusion-model-of-human-antibody-mediated-rejection/. Accessed May 18, 2025.« Back to 2019 American Transplant Congress