Novel Ex-Vivo Thrombolytic Reconditioning of Kidneys Retrieved 4 to 5 Hours After Circulatory Death

Abstract

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.

Long-term Transplant Function After Thrombolytic Treatment Ex Vivo of Donated Kidneys Retrieved 4 to 5 H After Circulatory Death

“…Thus, by removing the fibrin clots ex vivo, using Lysplasminogen and tPA, and preventing fibrin reformation, using AT-III, abciximab, and argatroban, kidneys subjected to circulatory arrest despite extensive WIT can be reconditioned during a 6-h oxygenated perfusion cycle in an ex vivo device. Despite retrieving these donor organs after warm ischemia times, which are considered unsuitable for transplantation by most active transplantation surgeons, very promising results were achieved, both functionally (creatinine and iohexol) and morphologically, with early functional recovery already after 10 d. 9 The implications of this novel technology in a clinical setting may be significant. Today, organ donation is performed at institutions in countries with highly advanced healthcare systems.…”

“…An autotransplantation model for uDCD has been developed to avoid allogeneic reactions. 9,14 Ethical Permit…”

“…The perfusion procedure has been recently described in detail. 9 See Supplemental Materials and Methods, SDC, http://links.lww.com/TP/C473. Thirteen pigs that received A-E) is seen to the left: (A) The left kidney, in green, was transplanted from the recipient (red pig) to the donor pig (blue pig) after (B) the right kidney of the donor had been removed and discarded.…”

“…the study protocol underwent autologous transplantation as previously described 9,14 and were observed for up to 3 mo. Two groups served as controls for the transplanted study group kidneys: II.…”

“…In a recent study, 9 we reported a novel method to salvage kidneys from extended uDCD. The protocol allowed the retrieval of uDCD kidneys in an ethically and clinically acceptable manner, without the need for extracorporeal circulation or rapid procurement by using a new thrombolytic treatment procedure utilizing Lys-plasminogen and tissue plasmin activator (tPA) (alteplase) ex vivo to clear the capillaries of the kidney from fibrin.…”