Pii: s0041-1345(02)02935-4

A Paired Study Comparing the Efficacy of Renal Preservation by
Normothermic Autologous Blood Perfusion and Hypothermic
Pulsatile Perfusion

M.S. Metcalfe, J.R. Waller, S.A. Hosgood, M. Shaw, W. Hassanein, and M.L. Nicholson THEREDUCTIONinmetabolicrateeffectedbyhypo- thermia constitutes the central tenet of traditional organ preservation.The antithesis of this approach is to provide for metabolic demand during normothermic pres- ervation. This latter strategy has two potential benefits.
First, if metabolic requirements are met during preserva- tion, then longer preservation with better posttransplant function may be achieved than for an organ suffering prolonged cold ischemia. Second, normothermic perfusion may allow ex vivo organ function to be restored and therefore assessed prior to transplantation. This may pro- vide a basis for viability assessment, thus reducing the risks of primary nonfunction of allografts. POPS (pulsatile organ The perfusion apparatus systems. (a) The POPS circuit.
perfusion system) (Transmedics, Boston, Mass, USA) is a (b) POPS control and monitoring and (c) the kidney in the organ new warm perfusion system for organs, using blood as the chamber. (d) kidneys on the RM3 system.
principle component of the perfusate. The aim of this study was to compare the efficacy of preservation of porcine kidneys by normothermic autologous blood perfusion and 2 and 4% CO2, the latter for pH homeostasis. The perfusate was supplemented by infusions of nutrients and colloid to replace hypothermic machine perfusion (RM3 system, Waters, urinary losses. The warm oxygenated blood prefused the kidney through the cannulated renal artery and drained back into a venousreservoir through a cannulated renal vein. The ureter was cannu- lated and urine drained away from the circuit (see Six large white pigs weighing 80 to 100 kg were sacrificed after electrical stunning followed by ex-sanguination, collecting theblood into 25,000 units of heparin. The kidneys were retrieved The RM3 system drives an acellular perfusate, Belzer’s machine through an anterior abdominal approach; the retrieval commenced perfusion solution (MPS), with a mean pressure of 40 mm Hg, immediately when the cardiac output ceased. Once retrieved the through a countercurrent cooling unit with the water reservoir kept kidneys were immediately perfused with cold (4°C) hyperosmolar cold with ice, maintaining a perfusate temperature of 3 to 8°C. The citrate solution and stored on ice for the 2 hours necessary to renal artery was cannulated for perfusion, with the renal vein transfer to the laboratory for perfusion.
effluent allowed to drain through the organ chamber back into aperfusate reservoir (see For both perfusion methods, the duration of perfusion was 16 hours, at the end of which their functions were assessed and One of each pair was perfused on the POPS system and the other compared. Cefuroxime (750 mg/L) was added to both perfusates to reduce the risk of microbial contamination.
From the Transplant Division, Faculty of Medical and Biolog- The POPS perfusion pressure was provided by an atraumatic ical Sciences, University of Leicester (M.S.M., J.R.W., S.A.H., pump, causing minimal erythrocyte lysis; the mean perfusate M.S., M.L.N.), Leicester, UK, and Transmedics Inc, Boston pressure was adjusted to 50 mm Hg. The perfusate was pumped through a heat exchanger, with the water bath set to maintain a This study was funded in part by Transmedics Inc.
perfusate temperature of 37°C, and a gas exchange unit, which Address reprint requests to Prof M.L. Nicholson, Department maintained the pO2 at 500 to 700 mm Hg. The gas for exchange was of Surgery, Leicester General Hospital, Leicester LE5 4PW, UK.
655 Avenue of the Americas, New York, NY 10010 Transplantation Proceedings, 34, 1473–1474 (2002) Table 1. Comparison Between the Kidneys Used in Both
At the end of the preservation period the kidneys were removedfrom their machines and perfused with cold (4°C) hyperosmolarcitrate solution. Then each was transferred to a POPS apparatusand perfused as above for 2 hours. During this assessment period,the ex vivo function of the kidneys was made by measuring urineoutput, perfusate flow rate and pressure, and urine and perfusateconcentrations of sodium, creatinine, protein, and glucose. From Results: (a) creatinine concentration ratios (b) creatinine these the intrarenal vascular resistance and urine-to-plasma con- clearances (c) sodium concentration ratios (d) glycosuria (e) centration ratios of sodium and creatinine were calculated. The proteinuria (f) intra-renal vascular resistance.
creatinine clearance was also calculated by multiplying the creati-nine concentration ratio by the urine output (mL/min).
crease oxygen carriage for renal preservation. They report improved renal transplant function of ischemically dam- aged organs (simulating non-heart-beating donors) com- Results are median (range) and statistical comparison was per- pared with conventional hypothermic perfusion.
formed using the Mann-Whitney U test. Significance is taken at the Hassanein et alreport encouraging results using the POPS for ex vivo preservation of porcine hearts and the ex vivo measurement of cardiac function.
Imber et alused autologous blood perfusion to preserve The warm ischemic times (from death to organ flushing) porcine livers, again with improved ex vivo measurements and cold ischemic times and kidney weights for both groups of function (bile secretion) compared with conventional are compared in There are no significant differ- Normothermic organ preservation may have the advan- The sodium and creatinine ratios, creatinine clearances, tages of improving the preservation itself and allowing proteinuria, glycosuria, and intrarenal vascular resistances pretransplant evaluation of function. These attributes were compared between the groups. The ability of kidneys would be particularly useful for organs procured from to concentrate creatinine and conserve sodium were signif- non-heart-beating donors, as these already suffer inevitable icantly better in the POPS-preserved kidneys than in the warm ischemic damage prior to retrieval and so tolerate RM3-preserved kidneys (P ϭ .03 for both) additional damage due to poor preservation.Also because Creatinine clearance was higher; vascular resistance, pro- of the warm ischemic insult they suffer, there is a pressing teinuria, and glycosuria were lower in the POPS-preserved need for reliable objective preoperative viability testing.
kidneys, although for these parameters the differences While the results are very encouraging, transplant exper- between the groups did not reach significance (P ϭ .7, .3, .3, iments are required to confirm that the ex vivo measure- ments of function correlate with posttransplant in vivo function. Autotransplant experiments similar to those de- scribed by Brasile would be ideal, as any alloimmune The POPS-preserved kidneys performed better than the response could be eliminated as a cause for posttransplant RM3-preserved organs, as measured by ex vivo indices of function. For creatinine and sodium concentration ratios The study used paired kidneys so that the groups were closely comparable. Larger groups may determine whether 2. Matsuno N, Sakurai E, Tamaki I, et al: Transplantation the other parameters measured were significantly different.
Hypothermic pulsatile perfusion preservation is thought to 3. Brasile L, Green E, Haisch C: Transplant Proc 29:3422, 1997 be superior to static cold storage, particularly for kidneys 4. Hassanein WH, Zellos L, Tyrrell TA, et al: J Thorac Cardio- retrieved from non-heart-beating donors.
5. St Peter SD, Imber CJ, Lopez I, et al: Br J Surg 89:609, 2002 Brasile et alhave used warm perfusion with an acellular 6. Tesi RJ, Elkhammas EA, Davies EA, et al: Clin Transplant perfusate containing perfluorochemical emulsion to in-

Source: http://transmedics.net/pdf/MetcalfKidneyManuscript.pdf

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