Table 1.
Experimental and clinical studies of machine perfusion of extended criteria donor kidney grafts.
| Studies | Model | Primary graft condition, N | MP time | Results and immunological aspects |
|---|---|---|---|---|
| ANIMAL STUDIES | ||||
| Treckmann et al. (40) | Porcine HMP vs. retrograde oxygen persufflation vs. SCS with autoTx | DCD; N = 7/group WIT: 1 h |
4 h | Malondialdehyde was dramatically increased in the MP kidneys on day 7, whereas levels in the other two groups were near normal values. The MP kidneys exhibited the most striking histological changes |
| Vaziri et al. (27) | Porcine HMP with Viaspan UW vs. KPS-1 vs. SCS without Tx | DCD; N = 7/group WIT: 1 h |
24 h | HMP demonstrated superiority over SCS independently of perfusion solution. Results suggested significant benefits on graft outcome, particularly evident on the chronic effects of IRI with a protection against chronic immune response, epithelial to mesenchymal transition and interstitial fibrosis and tubular atrophy |
| Thuillier et al. (41) | Porcine HMP ± hyperoxia with Tx | DCD; N = 4/group WIT: 1 h |
22 h | HMP with oxygen showed signs of higher quality and better function. Furthermore, the typical lesions of chronic graft loss were reduced, confirming improved ability to recover from the IRI |
| Stone et al. (1) | Porcine NMP without Tx |
N = 10 CIT: 2 h |
6 h | NMP initiated an inflammatory cytokine storm (especially IL-6, IFN-γ, and CXCL-8) and induced donor-derived leukocyte mobilization and removal prior to kidney Tx |
| Kasil et al. (42) | Porcine HMP ± M101 (2 g/L) ± hyperoxia with autoTx | DCD; N = 6/group WIT: 1 h |
23 h | The M101 improved the HMP effect upon kidney recovery and late graft outcome. The infiltration of mast-cell leukocyte was nearly absent, leading to reduced fibrosis level in the kidney. Excess supply of oxygen has not improved the results |
| HUMAN STUDIES | ||||
| Reznik et al. (43) | HMP vs. SCS with Tx | Uncontrolled DCD; N = 17 vs. 21 WIT: 42.7 ± 1.6 |
12 h | A considerable number of complications and the negative effects, including acute rejection, correlated with the SCS group of kidneys |
| Treckmann et al. (44) | HMP vs. SCS with Tx | ECD; N = 91/group Median age: 66 y CIT: 13 h |
n.d. | HMP preservation clearly reduced the risk of DGF and improved 1-year graft survival and function in ECD kidneys, while acute rejection rate was similar (17 vs. 16%, respectively) |
| Tozzi et al. (32) | HMP vs. SCS with Tx | Nyberg Score class C or D (donors mean age 67 ± 7 years); N = 10 vs. 13 CIT: 70 ± 25 min |
12 ± 4 h | The levels of early inflammatory cytokines (TNF-α, IL-2, and IL-1β) were decreased in HMP group in perfusion and preservation liquid; however, there was a non-significant difference comparing sICAM-1 |
| Nicholson et al. (45) | NMP vs. SCS with Tx | ECD; N = 10 vs. 47 CIT: ~11 h |
63 ± 16 min | The incidence of acute rejection was similar in both groups (27.7 vs. 23.4%), while the delayed graft function rate was significantly reduced in the NMP group (5.6 vs. 36.2%) |
| Wszola et al. (46) | HMP vs. SCS | ECD vs. standard criteria donors; N = 62 | 24 h | MP influenced gene expression related to hypoxia during reperfusion and may improve the long-term results of kidney Tx |
| Wang et al. (47) | HMP vs. SCS with Tx | DCD and ECD; N = 24/group | 5.86 ± 2.8 h | HMP reduced the incidence of DGF in DCD kidneys, and this effect is greater for ECD kidneys. Acute rejection rate was non-significantly different (4.1 vs. 8.3%, respectively) |
| Gallinat et al. (48) | End-ischemic HMP vs. SCS alone with Tx | ECD; N = 43/group Mean age: 66 vs. 67 years CIT: 13.4 vs. 12.1 years |
1.6–12.8 h | PNF and DGF were 0 vs. 9.3% and 11.6 vs. 20.9%. There was no statistically significant difference in 1-year graft survival, while rejection rate within 3 months post Tx was significantly higher in the end-ischemic HMP group (38.5 vs. 10%, respectively) |
| Weissenbacher et al. (49) | NMP without Tx | DCD and DBD; N = 11 WIT: 16.2 ± 10 CIT: ~35 h |
24 h | Demonstrated ability to maintain the condition of donor kidneys of ECD quality for long enough to carry out viability assessment and increase the feasibility to exploit this important source of donor organs |
| Ruiz-Hernández et al. (50) | Partial vs. total HMP with Tx | ECD; N = 119 vs. 74 Median age: 76.9 vs. 69.9 years CIT: 18.4 vs. 16.3 years |
>4 h | There is a trend that complete HMP reduces the risk of DGF and improves 1-year graft survival in ECD kidneys |
| Savoye et al. (51) | HMP vs. SCS with Tx | ECD; N = 801 vs. 3,515 Mean age: 63.9 vs. 62.7 years CIT: 16.9 vs. 17.4 h |
n.d. | Results confirmed the reduction in DGF occurrence among ECD kidneys preserved by HMP |
CIT, cold ischemia time; CXCL, C-X-C motif chemokine ligand; DGF, delayed graft function; ECD, extended criteria donor; DCD, donation after circulatory death; HMP, hypothermic MP; IFN, interferon; IL, interleukin; IRI, ischemia–reperfusion injury; MP, machine perfusion; NMP, normothermic MP; SCS, static cold storage; sICAM, soluble intracellular adhesion molecule; Tx, transplantation; WIT, warm ischemia time; UW, University of Wisconsin solution; PNF, primary graft nonfunction; DBD, donor after brain death.