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 June 26, 2019.
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