Rutger Ploeg - The Netherlands - Tuesday 29 -Experience in DCD Programs logistics, legal and ethical aspects
1. Nuffield Department of Surgical Sciences Oxford Transplant Centre United Kingdom DCD as the last Resource … Can we make Untransplantable Transplantable ? Rutger J. Ploeg MD PhD FRCS
2. DCD: Are we running in the right direction … ? … And if so, can we protect the donor organs ? And also: Are we allowed to repair ?
5. Effects of Cerebral Injury and Brain Death Decrease of function Inflammation with upregulation selectins & EC Pro-coagulatory activation Von Willebrand Factor
10. Complement Activation & Inhibition BD and Kidney Tx Model in the Rat Damman, Seelen & Hoeger, Yard; Transpl Immunology 2011
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13. How Effective is the Wash-out? Temperature & Rate Pig kidney: Systemic cold flush with aortic canulation Human kidney temp. Human liver temp.
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15. Machine Preservation Trial MP vs. CS in Kidney Transplantation in collaboration with Eurotransplant The European Multicenter Trial on Kidney Preservation Machine Perfusion versus Cold Storage 3 Parts: Overall Study, DCD Study & ECD Study Overall Study: NEJM 2009; DCD Study: Ann Surg 2010; ECD Study: Transpl Int 2011
16. Cold Storage vs. Machine Perfusion Donor Recipient 1 Recipient 2 November 1, 2005 – August 17, 2007
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18. Results: Logistic regression (DGF) Jochmans et al. Ann Surg 2010 Variable Odds Ratio (95% CI) p-value MP vs. CS Cold Ischemia Time HLA MM Recent PRA Recipient age Donor age Re-/ first Tx Length preTx dialysis 0.476 (0.239 - 0.949) 1.118 (1.028- 1.215) 1.073 (0.761- 1.514) 1.032 (0.992- 1.074) 1.031 (1.000- 1.062 ) 1.025 (0.997- 1.055) 1.051 (0.497- 2.225) 1.085 (0.927-1.271) 0.035 0.009 0.688 0.123 0.048 0.083 0.897 0.310
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20. Temperature ? Oxygen ? Liver and Kidney Machine Perfusion G MPs Prototype: Van der Plaats ‘ t Hart Test Pig Model: Maathuis - Minor, Bonn - Fondevilla, Barcelona
21. Leipzig 2007 * Folds to Control Regenerative capability DCD Pig Model with Extended Cold Ischemia: Kidney Tx HMP with & without Oxygen After 60 min Warm Ischaemia
22. Serum Creatinine (µmol/L) * * * * DCD Pig Model with Extended Cold Ischemia: Kidney Tx HMP with & without Oxygen After 60 min Warm Ischaemia INSERM, Poitiers – Thierry Hauet
29. EPO & TNF: Counteracting Cytokines Courtesy Dr. A. Cerami
30. Unilateral warm ischemia for 45 min followed by reperfusion. Sampling catheter in ureter. ARA 290 10 nmol/kg (~ 10ug/kg; via jugular vein) at 0, 2, 4, and 6 h. N=4 each group ARA 290 improves Kidney Function after Ischemia in the Pig Ploeg & Leuvenink, 2009
Human donors: Significant C3 induction as a direct result of brain death with no additional C3 gene expression due to injury caused by cold ischemia or reperfusion. (confirming our rat data)
Background: C3 is the central component of the complement system on which all activation pathways (Classical, alternative and lectin) converge. Mice knock-out C3 kidneys have significant better survival rates after transplantation compared to wild-type kidneys. (allograft model: 100 days vs 10 days) Significant upregulation of complement C3 gene expression in the rat brain death model after 4 h of brain death.
