Background. Due to organ shortage, many patients do not receive donor organs. The present novel thrombolytic technique utilizes organs from donors with uncontrolled donation after circulatory deaths (uDCD), with up to 4–5 h warm ischemia, without advanced cardiopulmonary resuscitation (aCPR) or extracorporeal circulation (EC) after death. Methods. The study group of pigs (n = 21) underwent simulated circulatory death. After 2 h, an ice slush was inserted into the abdomen. Kidneys were retrieved 4.5 h after death. Lys-plasminogen, antithrombin-III (ATIII), and alteplase (tPA) were injected through the renal arteries on the back table. Subsequent ex vivo perfusion at 15 °C was continued for 3 h, followed by 3 h with red blood cells (RBCs) at 32 °C. Perfusion outcome and histology were compared between uDCD kidneys, receiving no thrombolytic treatment (n = 8), and live donor kidneys (n = 7). The study kidneys were then transplanted into pigs as autologous grafts with a single functioning autologous kidney as the only renal support. uDCD control pigs (n = 8), receiving no ex vivo perfusion, served as controls. Results. Vascular resistance decreased to <200 mmHg/mL/min (P < 0.0023) and arterial flow increased to >100 mL/100 g/min (P < 0.00019) compared to controls. In total 13/21 study pigs survived for >10 days, while all uDCD control pigs died. Histology was preserved after reconditioning, and the creatinine level after 10 days was next to normal. Conclusions. Kidneys from extended uDCD, not receiving aCPR/EC, can be salvaged using thrombolytic treatment to remove fibrin thrombi while preserving histology and enabling transplantation with a clinically acceptable early function.

Large animal studies of long-term ischemia reperfusion are hampered by the use of immunosuppressive drugs to inhibit the influence of the allogeneic response. In small animals, this can be controlled by using inbred strains of the animal. For obvious reasons, this is not possible in large animals such as pigs. Since studies in pigs usually are the last step before first-in-man studies, this remains a problem trying to resemble a clinical situation. In the following short paper, we describe a novel auto kidney transplantation model that can be used for long term ischemia reperfusion studies. We also suggest a control setting to balance out the possible influence of an increased surgical trauma.

M.O. participated in the research design, wrote the article, performed the research, contributed new reagents and analytical tools, and collected and analyzed the data. D.A. participated in cowriting the article, performing the research, and collecting and analyzing the data. N.B.N. participated in the performance of the research. D.B. participated in the performance of the research, collection, and analysis of the data, G.T. participated in the performance of the research, and analyzed the data. G.U.P. performed the research and collected data. M.J. participated in data analysis. D.O., M.A.B., and O.H. participated in writing the article and data analysis. J.M.S. wrote the article and analyzed the data. All the authors provided critical feedback and helped shape the research.

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