Analysis of machine perfusion benefits in kidney grafts: a preclinical study

<p>Abstract</p> <p>Background</p> <p>Machine perfusion (MP) has potential benefits for marginal organs such as from deceased from cardiac death donors (DCD). However, there is still no consensus on MP benefits. We aimed to determine machine perfusion benefits on kidney grafts.</p> <p>Methods</p> <p>We evaluated kidney grafts preserved in ViaspanUW or KPS solutions either by CS or MP, in a DCD pig model (60 min warm ischemia + 24 h hypothermic preservation). Endpoints were: function recovery, quality of function during follow up (3 month), inflammation, fibrosis, animal survival.</p> <p>Results</p> <p>ViaspanUW-CS animals did not recover function, while in other groups early follow up showed similar values for kidney function. Alanine peptidase and β-NAG activities in the urine were higher in CS than in MP groups. Oxydative stress was lower in KPS-MP animals. Histology was improved by MP over CS. Survival was 0% in ViaspanUW-CS and 60% in other groups. Chronic inflammation, epithelial-to-mesenchymal transition and fibrosis were lowest in KPS-MP, followed by KPS-CS and ViaspanUW-MP.</p> <p>Conclusions</p> <p>With ViaspanUW, effects of MP are obvious as only MP kidney recovered function and allowed survival. With KPS, the benefits of MP over CS are not directly obvious in the early follow up period and only histological analysis, urinary tubular enzymes and red/ox status was discriminating. Chronic follow-up was more conclusive, with a clear superiority of MP over CS, independently of the solution used. KPS was proven superior to ViaspanUW in each preservation method in terms of function and outcome. In our pre-clinical animal model of DCD transplantation, MP offers critical benefits.</p

Potential of Donation After Unexpected Circulatory Death Programs Defined by Their Demographic Characteristics

BACKGROUND. Donation after unexpected circulatory death (uDCD) donors are often suggested to increase the number of donor organs. In 2014, a uDCD protocol was implemented in three transplant centers in the Netherlands which unfortunately did not result in additional transplantations. This study was initiated to identify demographic factors influencing the potential success of uDCD programs. METHODS. Dutch resuscitation databases covering various demographic regions were analyzed for potential donors. The databases were compared with the uDCD implementation project and successful uDCD programs in Spain, France, and Russia. RESULTS. The resuscitation databases showed that 61% of all resuscitated patients were transferred to an emergency department. Age selection reduced this uDCD potential to 46% with only patients aged 18–65 years deemed eligible. Of these patients, 27% died in the emergency department. The urban region of Amsterdam showed the largest potential in absolute numbers (52 patients/y). Comparison with the uDCD implementation project showed large similarities in the percentage of potential donors; however, in absolute numbers, it showed a much smaller potential. Calculation of the potential per million persons and the extrapolation of the potential based on the international experience revealed the largest potential in urban regions. CONCLUSIONS. Implementation of a uDCD program should not only be based on the number of potential donors calculated from resuscitation databases. They show promising potential uDCD percentages for large rural regions and small urban regions; however, actual numbers per hospital are low, leading to insufficient exposure rates. It is, therefore, recommendable to limit uDCD programs to large urban regions

Improved short and long term function of DCD kidneys with oxygenated machine perfusion

ORAL SESSION 20 : Improving preservation in transplant organsInternational audienc

Preclinical Modeling of DCD class III Donation and Evaluation of the Most Adapted Preservation Protocol: Paving the Way for the Increased Use of this Challenging Donor Type

International audienceCurrent organ shortage imposes the need to expand the donor pool. Deceased after circulatory death (DCD) donors are a promising source, and in particular the Maastricht class III (arrest subsequent to cessation of life support in the hospital). While current results from class III are positive, the unavoidable expansion of inclusion criteria will severely impact organ quality and increase the complication rate. It is thus of paramount importance to study this donor type in a controlled model in order to explore preservation protocols and be ready for future challenges. We endeavored to reproduce the clinical conditions of DCD class III in the Large White pig and used this novel model to compare the performances of machine and static preservation protocols. Through a combination of: -pharmacological calcium blockers and chronotropes; -decreased ventilation; and -animal positioning; we successfully reproduced the conditions of DCD class III in a large animal, obtaining perfusion pressures and functional warm ischemia (hypoperfusion) levels on par with situations encountered in the clinic. Important functional and histological impacts were recorded. Organs from these animals were then collected and preserved through 3 protocols for 24h: static preservation (University of Wisconsin), machine preservation (Lifeport), static (20h) combined to machine (4h). Isotransplanted animals were then followed for 3 months. Preliminary findings indicate that the level of damage withstood by the organs could not be compensated by machine perfusion alone. An extended analysis will be presented and exploration of alternative preservation protocols will be discussed. This model could be invaluable to investigate new management alternative for extended criteria class III DCD donors, such as normothermic regional circulation and/or pharmacological supplementation