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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Inserm U927, Poitiers, Poitiers F-86021, France.
Nader
N
Vaziri
Raphaël
R
Thuillier
Frederic D
FD
Favreau
Michel
M
Eugene
Serge
S
Milin
Nicolas P
NP
Chatauret
Thierry
T
Hauet
Benoit
B
Barrou
D000818:Animals; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D005355:Fibrosis / Q000209:etiology; D007111:Immunity, Cellular / Q000502:physiology; D007668:Kidney / Q000502:physiology; D016030:Kidney Transplantation / Q000379:methods; D008297:Male; D009926:Organ Preservation / Q000295:instrumentation* / Q000379:methods*; D010477:Perfusion / Q000295:instrumentation* / Q000379:methods*; D020127:Recovery of Function / Q000502:physiology; D018570:Risk Assessment; D013552:Swine; D014019:Tissue Donors; D014022:Tissue Survival / Q000502:physiology; D014181:Transplantation Immunology
Ann Transplant. 2004;9(2):31-2
15478913
Transpl Int. 2010 Jun;23(6):561-70
20074082
Am J Physiol Renal Physiol. 2009 Jul;297(1):F177-90
19386723
J Urol. 2008 Jul;180(1):19-30
18485395
J Clin Invest. 2003 Dec;112(12):1776-84
14679171
Am J Transplant. 2010 Jan;10(1):30-9
19958330
Transplantation. 2005 May 27;79(10):1358-61
15912104
Transplantation. 2010 Sep 27;90(6):612-21
20865816
Transplantation. 1985 Dec;40(6):659-61
3907039
Transplantation. 2010 Apr 15;89(7):830-7
20098357
Clin Transplant. 2003 Aug;17(4):293-307
12868986
Ann Surg. 2010 Nov;252(5):756-64
21037431
Transplantation. 2002 Dec 27;74(12):1715-20
12499887
Surgery. 2009 Oct;146(4):686-94; discussion 694-5
19789028
Transplant Proc. 2008 May;40(4):1023-6
18555105
Cryobiology. 2009 Aug;59(1):19-23
19345683
Transplantation. 1997 Apr 15;63(7):917-21
9112339
Transplantation. 2006 Mar 15;81(5):643-54
16534463
Circ Shock. 1989 Sep;29(1):27-39
2791216
Am J Transplant. 2010 Sep;10(9):1991-9
20883534
Semin Nephrol. 2007 May;27(3):250-9
17533004
Transplantation. 2004 Aug 15;78(3):333-7
15316359
Arch Environ Contam Toxicol. 1986 Jul;15(4):343-7
2874775
Am J Transplant. 2005 Mar;5(3):500-9
15707404
Nephrol Dial Transplant. 2010 Jun;25(6):1980-6
20167568
Artif Organs. 2009 Jul;33(7):565-70
19566736
N Engl J Med. 2009 Jan 1;360(1):7-19
19118301
Transplant Proc. 2001 Feb-Mar;33(1-2):847
11267094
JAMA. 1984 Nov 2;252(17):2432-4
6148429
Pediatr Nephrol. 2009 Aug;24(8):1465-71
18584214
Transplant Proc. 2007 Jun;39(5):1323-5
17580131
Transplantation. 2005 May 15;79(9):1195-9
15880069
Am J Kidney Dis. 2009 Sep;54(3):410-2
19560851
Cryobiology. 2010 Jul;60(3 Suppl):S20-35
19857479
Am J Physiol Renal Physiol. 2004 Aug;287(2):F181-7
15271685
Am J Transplant. 2009 Sep;9(9):2004-11
19624569
Am J Transplant. 2004 Sep;4(9):1490-4
15307836
J Investig Med. 2004 Jul;52(5):299-309
15551652
Am J Physiol Renal Physiol. 2002 Jun;282(6):F1140-9
11997331
Transplant Proc. 2005 Jan-Feb;37(1):348-9
15808639
N Engl J Med. 2009 Jan 1;360(1):78-80
19118308
Am J Physiol Renal Physiol. 2007 Mar;292(3):F1082-93
17341718
Transplant Rev (Orlando). 2008 Jan;22(1):1-5
18631853
Br J Surg. 2010 Mar;97(3):349-58
20095019
Transplantation. 1988 Apr;45(4):673-6
3282347
J Appl Physiol (1985). 1992 Oct;73(4):1467-73
1332933
Lancet. 1992 Jul 18;340(8812):129-37
1352564
J Surg Res. 2011 Nov;171(1):283-90
20421113
Am J Transplant. 2009 Mar;9(3):527-35
19191769
J Am Soc Nephrol. 2003 Jun;14(6):1662-8
12761269
Transplantation. 2003 Jul 15;76(1):37-43
12865783
Transplantation. 2000 Mar 15;69(5):842-6
10755537
Am J Transplant. 2005 Jun;5(6):1367-74
15888043
Am J Transplant. 2010 Sep;10(9):1955-6
20883530
Am J Transplant. 2007 Aug;7(8):1942-7
17617857
Cell Biochem Biophys. 2008;52(3):125-38
18982455
Int J Artif Organs. 2009 Oct;32(10):728-38
19943234
Ann Transplant. 2009 Jan-Mar;14(1):14-7
19289991
Transplantation. 2007 May 27;83(10):1289-98
17519776
Transplant Proc. 1997 Dec;29(8):3489
9414806