Normothermic Recirculation of Non Heart Beating Donor Kidneys

Coordinators: H.G.D. (Henri) Leuvenink (h.g.d.leuvenink@chir.umcg.nl)

J.J. (Jacco) Zwaagstra (j.j.zwaagstra@chir.umcg.nl)

C. (Cyril) Moers (c.moers@chir.umcg.nl)

Most deceased donors are patients on the ICU who meet the legal criteria for brain stem death. Organ retrieval can be performed under controlled conditions, since circulation and ventilation are intact until cold systemic perfusion of the donor. Due to rising numbers of patients on the waiting list for a donor kidney, renal grafts are increasingly procured from non heart beating (NHB) donors as well. These are patients who have suffered irreversible brain injury, but do not meet legal brain death criteria. Hence, organ donation can only be initiated after withdrawal of treatment, followed by cardiac death. As a result of the inevitable time interval between cardiac arrest and start of organ retrieval, NHB kidneys are exposed to considerable warm ischemic injury. After transplantation, these renal grafts show an inferior function, compared to kidneys derived from heart beating, brain dead donors. In order to improve functional outcome of NHB donor organs, various interventions are studied by our group. One promising intervention is normothermic recirculation (NR): Directly after warm ischemic injury, the donor is artificially recirculated for a short period (1-2 hrs) with warm oxygenated blood. After NR, the organs are cooled as usual, procured and transported on ice to their respective recipient. We hypothesize that a short interval of NR, instead of immediate organ cooling, may partly restore the organ’s energy status and upregulate cytoprotective and reparative mechanisms before hypothermic organ preservation commences. To test this theory, we have designed an animal experiment in which rat kidneys are first exposed to 15 or 30 minutes of warm ischemia, and then to 1 or 2 hours of NR, versus a control group without NR. Next, the kidney is cold stored for 24 hours and transplanted into a recipient animal. Recipient rats will survive for one or 14 days. Analyses focus on characterization of kidney injury, upregulation of cytoprotective and reparative mechanisms in the renal tissue, and on kidney graft function up to 14 days after transplantation. Among the techniques we use are histology, immunohistochemistry, real-time PCR, western blot, and biochemical analyses of tissue, plasma, and urine.

The student will be involved in the experiments and analyses mentioned above. In addition, the student will have the opportunity to witness a living (human) kidney donation and transplantation in the OR, and to observe any deceased donor procurement or transplant procedure in our hospital, when applicable.