1 / 24

Ex Vivo Normothermic Preservation in Deceased Donor Renal Transplantation

Ex Vivo Normothermic Preservation in Deceased Donor Renal Transplantation. Richard Perez, MD Transplant Surgery UC Davis Medical Center. Deceased Donor Kidney Transplantation: A Model of Ischemia-Reperfusion Injury. Potential Deceased Donor

fpaine
Download Presentation

Ex Vivo Normothermic Preservation in Deceased Donor Renal Transplantation

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Ex Vivo Normothermic Preservation in Deceased Donor Renal Transplantation Richard Perez, MD Transplant Surgery UC Davis Medical Center

  2. Deceased Donor Kidney Transplantation: A Model of Ischemia-Reperfusion Injury Potential Deceased Donor Hypotension, shock, acute inflammation, kidney injury Brain death or DCD Ex vivo Organ preservation – Hypothermia and hypoxia Recipient Vascular anastomosis with re-perfusion injury

  3. Disadvantages of hypothermic preservation • Ongoing low level metabolism/tissue breakdown • Loss of energy stores • Predictions of ultimate viability and function limited in highest risk marginal donors • Not metabolically active so intervention for reconditioning/repair is limited • Many high risk kidneys discarded

  4. Ex vivo normothermic perfusion for organ preservation/pre-conditioning • Maintain body temperature • Oxygenation • Support aerobic metabolism • Normal physiologic function • Advantages • Restore ATP • Able to assess organ function • Minimize cold ischemia injury • Regeneration and repair initiated?

  5. Can ex vivo normothermic perfusion preservation be used to “rescue” discarded kidneys deemed “not transplantable” (2500/year)?

  6. Hosgood / Nicholson, Transplantation 2011

  7. Normothermic Perfusion System Pressure Display Pressure probe Medtronic Console Urine Collection Flow probe Heat Exchanger, 370C Venous Reservoir Oxygenator Centrifugal Pump

  8. UC Davis Pre-Clinical Ex Vivo Normothermic Renal Perfusion • April 2013 - First sheep kidney perfused • Jan 2014 - First human kidney perfused • Jan 2014 - Nov 2015 - 53 human kidneys perfused • Donor ages: 1 day – 78 years old • Perfusion times: 1 - 12 hours

  9. Ex Vivo Normothermic Perfusion to Assess and Repair Kidney Ischemia-Reperfusion Injury I Palma, Y Smolins, J Woloszyn, et al. UC Davis Medical Center Academic Surgical Congress 2015

  10. Study Design Deceased donors (n=4) presumed suitable for transplantation Met criteria for discard Paired kidneys (n=8) entered into study Whole blood EVNP to simulate clinical allograft reperfusion (n=4) Packed RBC EVNP to test optimized normothermic preservation (n=4)

  11. Donor Characteristics

  12. Human Kidney Pre-Perfusion 1 hour 2 hours 3 hours 10A- WB 10B- PRBCs

  13. Improved Hemodynamics with Optimized Normothermic Perfusion Academic Surgical Congress 2015

  14. Ex vivo normothermic perfusion increases urine production Academic Surgical Congress 2015

  15. Decreased injury biomarkers with optimized normothermic perfusion

  16. Ex vivo Normothermic Perfusion for Assessment of High Risk Deceased Donor Kidneys for Transplantation S Kabagambe, I Palma, Y Smolin, T Boyer, IP Palma, J Sageshima, Csanthanakrishnan, C Troppmann, J McVicar, R Perez UC Davis Medical Center Cutting Edge of Transplantation 2016

  17. What criteria can we use to determine if an organ is transplantable? • Retrospective review of locally discarded kidneys • Study period: June 2014 – Oct 2015 • Kidneys provisionally accepted for transplant but turned down due to biopsy and/or hypothermic perfusion parameters • Placed on EVNP research protocol • Assessment of gross appearance, blood flow, and urine output

  18. n=6 Globally pink and well perfused High blood flow Good urine output Probably transplantable with Low Risk n=2 Pink, well perfused but patchy High blood flow Low urine output Possibly transplantable with Moderate Risk n=1 Pink and patchy Low blood flow No urine output Deemed not transplantable

  19. Prospective clinical study of ex vivo normothermic perfusion in high risk deceased donor renal transplantation • Purpose • Demonstrate safety and feasibility of EVNP • Comparison of standard of care hypothermic machine perfusion versus hypothermic perfusion + short additional period (2-4 hrs) of ex vivo normothermic perfusion prior to transplantation • Establish a normothermic platform for further studies

  20. Clinical trial of ex vivo normothermic perfusion in renal transplantation • Inclusion criteria: Paired kidneys from donors with increased risk for DGF • Donors with acute renal injury (Creat > 2.0) • Donation after circulatory death • Prolonged cold ischemia time (>36hrs) • Donors with KDPI >70%

  21. Clinical trial of ex vivo normothermic perfusion in renal transplantation • Clinical protocol • Standard hypothermic machine perfusion preservation to paired kidneys from high risk donors • Control kidney transplanted after cold machine perfusion • Study kidney to have additional 2-4 hours of normothermic perfusion just prior to implantation of organ

  22. Ex Vivo Normothermic Perfusion: Future Directions • Routine assessment of high risk/marginal organs • Normothermic perfusion as a means to intervene and optimize organ function pre-transplant • Pharmacologic • Gene therapy • Stem cells • Development of “Organ Repair Centers”

  23. Participating OPOs • One Legacy • Sierra Donor Services • Donor Network of Arizona • LifeShare • Gift of Life Philadelphia • Gift of Hope Illinois • Life Link of Florida • Life Share Oklahoma • Life Center Northwest • LifeNet Health • Midwest Transplant Network • Southwest Transplant

More Related