Three‐Month Graft Survival of Kidneys Retrieved 4,5 Hours After Circulatory Death

Abstract

Background: The availability of an increased proportion of organs from donors after circulatory death (DCD) could solve the organ shortage globally. We present a model of extended uncontrolled DCD (uDCD), allowing sufficient time for the consent procedure in most countries. A novel reconditioning technique allows successful transplantation after prolonged warm ischemia of kidneys from uDCD donors. Methods: Two hours after circulatory death, ice slush was inserted into the abdomen of pigs. Donor organs were then retrieved 4.5 hour after death, and treated on the back-table by injecting Lys-plasminogen, antithrombin-III (AT-III), and alteplase (tPA) through the renal arteries. The kidneys were then perfused with an albumin-rich solution at 15 °C and 20 mmHg for 3 hours. Washed erythrocytes were added to the solution after increasing temperature to 32 °C and pressure to 30 mmHg, continuing the perfusion for another three hours. Argatroban and abciximab were added to inhibit re-thromboses. Reconditioning (study group) kidneys were transplanted into pigs using a novel auto-transplant technique with a single functioning autologous kidney and observed for three months. Sham-treated pigs underwent contra-lateral transplantation of the left kidney after removing the right kidney under the same anesthesia conditions and trauma as study group pigs. Findings: During perfusion, vascular resistance decreased to 100ml/100g/min, significantly higher (p < 0.00018) than kidneys not receiving thrombotlytic treatment. At 3 months post-transplant, 4/6 study and 4/6 control pigs survived. Serum creatinine and renal histology did not differ between the groups. Interpretation: We present a novel method to salvage kidneys from extended uDCD, enabling subsequent transplantation after ex-vivo reconditioning, in a clinically acceptable manner. Funding Information: Supported by grants from IngaBritt and Arne Lundbergs Research Foundation; LUA ALF Grant; The Gelin Foundation and Hans-Gabriel and Alice Trolle Wachtmeister Foundation for Medical Research. Declaration of Interests: MO is the inventor of several patents. None of the other authors reported any potential conflicts of interest Ethics Approval Statement: The Regional (Malmo/Lund) Animal Experiment Ethics Committee approved the study (Dnr 5.8.18‐13977/2018; Dnr 5.8.18‐09474/2019; Dnr 5.8.18‐09182/2020). All animals were housed and cared for in compliance with the “Principles of Laboratory Animal Care” formulated by the National Society for Medical Research and the “Guide for the Care and Use of Laboratory Animals” prepared by the Institute of Laboratory Resources and published by the National Institute of Health (NIH, Publication No 86‐23, revised 1996).