New Perspective for Expanding Donor’s Pool - Resuscitation Kidney In Uncontrolled Donors by Normothermic Perfusion “In Situ” with Oxygenation and Leucocyte Depletion Saint-Petersburg, Russia State Research Institute for Emergency, ISODP-2011 Buenos-Aires, Argentina O.Reznik, A. Skvortsov, A.Reznik, Y.Moysyuk, S.Bagnenko, and S.Gautier

The authors don’t have the conflict of interests The design of this study, protocols of perfusion, and procurement and transplantation procedures were approved by the Scientific Board and Ethics Committee of the Saint Petersburg State Research Institute for Emergency (Decision 7/0615/09) and authorized for clinical application by the Federal Advisory Service of the Health Ministry of the Russian Federation (Resolution N2010/299)

In the US, the number of potential uncontrolled donors after cardiac death was estimated at 22,000 per year in 2006 IOM: Organ Donation: Opportunities for Action. Washington, DC: National Academies Press; 2006 Hanto DW, Veatch RM. Uncontrolled Donation after Circulatory Determination of Death (UDCDD) and the Definition of Death. Am J Transplant 2011; 11(7): Hoogland ERP, et al. Kidney Transplantation from Donors after Cardiac Death: Uncontrolled versus Controlled Donation. AJT 2011; 11(7): Wall SP, et al. Derivation of the Uncontrolled Donation after Circulatory Determination of Death Protocol for New York City. Am J Transplant 2011; 11(7): Introduction

background number of patients died form irreversible sudden asystole was 173 in 2009 The number of patients died form irreversible sudden asystole was 173 in 2009 in Saint Petersburg in Saint Petersburg Most of potential grafts from uDCD are lost due to irreversible ischemic damage during warm ischemic time The main task our work was the development procurement protocol which would lead to the organ resuscitation after ischemical damage and due to this expanding the donor pool

“Compilation approach” Sanchez-Fructuoso A.I.,et al. Non-heart beating donors: experience from the Hospital Clinico of Madrid, J. Nephrol;2003;16(3); Steen S., Ingemansson R. et. al. First Human Transplantation of Nonacceptable donor lung after reconditioning ex vivo Ann of Thor Surgery,2007,83(6), Talbot D. et al. How to improve the quality of kidneys from non- heart-beating donors: a randomized controlled trial of thrombolysis in non-heart-beating donors,Transplantation,2003,76(12), Jamieson R. W., Friend P. J. Normothermic organ preservation, Tr Rev,2006,Vol. 20,P Nicholson M. L., Simon J. F., Harper L.W. et. al. The Effect of Warm Ischemic Time on Renal Function and Injury in the Isolated Hemoperfused Kidney,Transplantation,2008,86(3), Fondevila C., et al., Am J Tr 2007;7;1849 Liver transplant using donors after unexpected cardiac death: novel preservation protocol and acceptance criteria

Sergei S. Brukhonenko, «Soviet Experiments in the Revival of Whole Organisms and Isolated Dog Head» 1927 Konstantinov I.E., Alexi-Meskishvili V.V. Sergei s. Brukhonenko: the Development of the First Heart-Lung Machine for Total Body Perfusion Ann. Thorac. Surg. – Vol P. 962 – 966. Probert W.R., Melrouse D.G. An Early Russian Heart-Lung Machine BMJ, 1960 April Р.104

material & methods material & methods New logistic procurement model Extracorporal perfusion circuit Perfusat (modificated donor’s blood) 17 uncontrolled donors, recipients of kidney from uDCD

Material and Methods: New Uncontrolled Donation Logistics Chain Warm Ischemic Time minutes

surgical femoral vessels access and three - lumen double balloon catheterization of abdominal region

Scheme of isolated abdominal perfusion procedure

Composition of perfusat Modificated donor blood (27°-32°C) U heparin 1,5 mln U streptokinase 400 ml perfluorocarbonic emulsion for primary filling of perfusion circuit is used the HTK-solution

Characteristic Value (percentage) (N = 17) Age, years43.6 ± 2.2 Gender: Male Female 14 (82.4%) 3 (17.6%) Cause of death: Brain injury Cerebrovascular disease 11 (64.7%) 6 (35.3%) Dopmine dose, mkg/kg/min6.82 ± 0.65 Creatinine, mg/dL1.48 ± 0.11 Diuresis during the last hour,0.35 ± 0.06 Warm ischemia, min68 ± 4 Donors characteristics

Donors’ Perfusion procedure data VariableValue (N = 17) Hemoglobin, g/L33.6 ± 3.75 Hematocrit0.32 ± 0.02 рН of perfusate7.0–7.37.0–7.3 Perfusion flow, initial, ml/min500 Perfusion flow, final, ml/min3500 Oxygen supply initial, ml/min150 Final oxygen supply, ml/min350 Average рО 2 * in perfusate, mmHg297.8 ± 27.5 Average рСО 2 ** in perfusate, mmHg99.8 ± 7.4 Duration NECP and LD***, min152.1 ± 6.9 Leukocyte count in perfusion contour, initial 16.4 ± 1.2 Leukocyte count in perfusion contour, final 0.77 ± 0.13 *рО 2 : partial pressure of oxygen **рСО 2 : partial pressure of carbon dioxide ***NECP and LD: normothermic extracorporeal perfusion and leukocyte depletion

Recipients characteristics CharacteristicValue (percentage) (N = 34) Age, years51.4 ± 1.3 Type of dialysis: Hemodialysis Peritoneal dialysis Mixed dialysis 28 (82.4%) 6 (17.6%) - Years on dialysis prior to transplant3.32 ± 0.33 Cause of end-stage renal disease: Glomerulonephritis Pyelonephritis Polycystic kidney 31 (91.2%) 1 (2.9%) 2 (5.9%) Cold ischemic time before transplantation, hrs 14.8 ± 0.67 Graft function: IGF DGF 11 (32.4%) 23 (67.6%) Number of dialysis/1 month for DGF group5.8 ± 0.96 Creatinine at 90 days, mg/dL2.4 ± 0.02 Creatinine at 1 year, mg/dL 1.81 ± 0.05 cGFR 3, ml/min/1.73 m ± 2.18 Acute rejection kidney/90 days2 (5.8%) Surgical complications1 (2.9%)

Conclusion The results of the 1-year follow-up of our initial clinical experience with this procedure provide evidence that transplantation of organs that are “ resuscitated ” using this method are satisfactory and meet the generally accepted criteria for graft survival and functioning. The implementation of NECP with oxygenation and leukocyte depletion allows expanding the donor pool due to inclusion of the resource of donors with unexpected cardiac death

Sergei Brukhonenko THANK YOU FOR YOUR ATTENTION