Objectives: The logistics of deceased-donor renal transplants are largely affected by cold ischemia time. However, to attain successful outcomes, other issues must be considered. Extending cold ischemia time to accommodate these issues would be valuable. We investigated the role of hypothermic machine perfusion to extend cold ischaemia time.

Materials and Methods: Deceased-donor kidneys were allocated to a storage method, depending on predicted time to operation. Kidneys to be transplanted from 8:00 AM to 8:00 PM in the transplant room remained in static cold storage. If predicted operating time was out of hours, the kidney was transferred to hypothermic machine perfusion and transplanted at the earliest opportunity on the dedicated transplant list.

Results: There were 74 kidneys transplanted from hypothermic machine perfusion and 101 kidneys from static cold storage. Median cold ischemia time was 23.85 hours in the hypothermic machine perfusion group, compared with 13 hours in the static cold storage group (P ≤ .0001). There were 20 kidneys (27%) from hypothermic machine perfusion that had delayed graft function, compared with 47 kidneys (47%) in the static cold storage group (P = .012). There were no other significant differences in graft or postoperative complications.

Conclusions: This study demonstrated that improved early graft outcomes can be achieved following longer cold ischemia time by using hypothermic machine perfusion rather than static cold storage. This effect is likely multifactorial including the inherent effects of hypothermic machine perfusion, improved recipient preparation, and possibly better perioperative conditions.

Key words : Kidney transplant, Organ preservation, Delayed graft function

Introduction

Cold ischemia time (CIT) is a major factor affecting early posttransplant graft function.^1-5 Nevertheless, many other factors must be considered and optimized to achieve the best outcomes in renal transplant, particularly when deceased-donor renal transplant is increasingly complex.

Most transplant units acknowledge that more deceased-donor kidneys that become available for transplant are marginal.^6,7 More extended criteria donor (ECD) kidneys are being used and these, along with donation after cardiac death (DCD) kidneys, are associated with a higher risk of delayed graft function (DGF) than standard criteria donor kidneys.^8-11

The recipient population of deceased-donor kidneys has become more challenging. Recipients are frequently older with significant comorbidity – these patients have previously been considered inappro-priate for transplant.^10,12,13 This is exacerbated by the observation that many patients with less comorbidity receive early, living-donor transplants. In conse-quence, it now is common experience that patients waiting for deceased-donor transplants have no living-donor option, and these patients have long histories of dialysis with its associated complications. Patients may also deteriorate between listing and admission for transplant.¹⁴ Optimizing all these patients during emergency admission for renal transplant can be problematic, and CIT may be prolonged because of the need for new investigations or interventions.

Deceased-donor organ transplant is frequently undertaken outside of normal working hours in an attempt to minimize CIT. In this time-critical situation, recipient issues may receive less attention than is optimal. Furthermore, in an attempt to minimize CIT, transplants may be performed on emergency operating lists staffed by general teams with limited experience in treating the specific needs of patients who have renal failure.^15,16 Such compromise carries the inherent risk that the care may fall below a level of excellence.

The fact that logistics and timing of deceased-donor renal transplant have largely been affected by CIT is one of the enduring tenets of transplant. Often CIT will override most other considerations. However, to achieve successful outcomes in increasingly complex donor-recipient combinations, recipient and logistic issues require equal consideration with CIT. Therefore, methods to extend CIT acceptably without affecting early graft function would be of value.

We have investigated the role of hypothermic machine perfusion (HMP) as a tool to extend CIT.

Materials and Methods

This study was performed in a large teaching hospital that provides a regional transplant service to a mixed demographic population of > 6 million (190 kidney transplants annually, including 120 transplants from deceased donors). The study objective was to evaluate whether graft function could be maintained or improved during long CIT using HMP, while simultaneously acquiring the benefits of an optimized recipient with improved use of logistics and expertise.

After procurement, deceased-donor kidneys arrived at the unit in static cold storage (SCS). Emergency operating theater space was available on a competitive basis with other specialties; therefore, it was not possible always to ensure a short CIT. Furthermore, emergency teams often consisted of staff members who did not regularly treat renal failure patients. Incoming transplant recipients had multifaceted medical problems and may have been treated at peripheral dialysis units. Accordingly, they often needed much preoperative reevaluation and preparation, including perioperative dialysis.

As a compromise to 24-hour operating theater availability, the unit had a dedicated renal transplant theater team available between 8:00 AM and 8:00 PM. When possible, such complex renal cases were directed toward this resource. In this study, as in normal departmental practice, the decision to transfer to HMP was based on donor-recipient readiness and theater availability. If the predicted time to theater was within elective hours (8:00 AM to 8:00 PM), the kidney was transplanted from SCS. If the predicted time to theater was outside these hours (8:00 PM to 8:00 AM), the kidney was transferred to HMP and transplanted at the earliest opportunity during elective hours on the dedicated transplant list. Data were collected prospectively for all deceased-donor kidneys accepted for transplant and included donor and recipient demographics, CIT, operative factors, and postoperative outcomes. Protocols conformed with the ethical guidelines of the 1975 Helsinki Declaration and were approved by the institutional ethics committee.

All HMP kidneys were preserved with a transporter (LifePort Kidney Transporter 1.0, Organ Recovery Systems, Chicago, IL, USA). Perfusion pressure was set at 30 mm Hg. All kidneys were perfused with 1 L cold perfusion solution (KPS-1 Kidney Perfusion Solution, Organ Recovery Systems). Temperature, perfusion pressure, flow, and resistance were monitored during perfusion time.

Outcome measures
The primary outcome measure was DGF, which was defined as the requirement for dialysis within postoperative week 1 following kidney transplant. Secondary outcomes were CIT, timing of surgery, HMP parameters, complications, length of hospital stay, and postoperative creatinine levels.

Statistical analyses
Data were analyzed with software (GraphPad Prism 6.0c, GraphPad Software, La Jolla, CA, USA) (IBM SPSS for Windows, Version 19.0, IBM Corp., Armonk, NY, USA). Continuous variables were expressed as arithmetic or geometric mean with 95% confidence interval or median and interquartile range. Comparisons of demographics and complication rates between HMP and SCS kidneys were made using Mann-Whitney test for continuous data or Fisher exact test for categorical data. The trends over time in resistance and creatinine levels were assessed using repeated measures analysis of variance, and the dependent variables were logarithm-transformed (base 10) where necessary. Values of P < .05 were considered indicative of statistical significance.

Results

During the observation period (January 2012 to December 2013 inclusive), 196 deceased-donor kidneys were accepted to the unit for transplant. Kidneys transplanted as part of a combined heart or liver transplant procedure were excluded (n = 5). There were 3 kidneys discarded due to severe atherosclerosis with an adverse donor history, small cystic kidney, and inadequate flush at organ recovery. No kidneys were discarded based on machine parameters. Pediatric cases also were excluded (n = 13). Of the 175 kidneys included in the study, 74 kidneys (42%) underwent HMP and 101 kidneys (58%) were transplanted from SCS.

Donors and recipients
Donor and recipient demographics showed that the 2 groups were well matched (Table 1). The HMP group had significantly lower frequency of DCD kidneys (Table 1).

Delayed graft function
The most frequently occurring graft complication was DGF, with 67 transplant recipients (38%) requiring dialysis within the first week (DGF: 20 HMP kidneys [27%]; 47 SCS kidneys [47%]; P = .012). For donation after brain death (DBD) kidneys only, 15 of 65 kidneys (23%) in the HMP group developed DGF compared with 30 of 75 kidneys (40%) in the SCS group (P = .046).

For DCD kidneys only, 5 of 9 kidneys (56%) in the HMP group developed DGF compared with 17 of 26 kidneys (65%) in the SCS group (P = .698).The median duration of DGF (time from operation to the last dialysis session) was 5 days for both storage groups (interquartile range: HMP, 2.25 to 6.75 d; SCS, 2.00 to 8.50 d; P = .628).

Cold ischemia time and timing of surgery
The median CIT in the HMP group was 23.85 hours (interquartile range, 19.30 to 26.62 h), significantly longer than the 13.00 hours (11.79 to 15.36 h) in the SCS group (P ≤ .0001). For DBD kidneys only, the median CIT in the HMP group was 24.18 hours (interquartile range, 20.73 to 26.93 h) compared with 13.32 hours (10.66 to 16.13 h) in the SCS group (P ≤ .0001).

For DCD kidneys only, the median CIT in the HMP group was 16.60 hours (interquartile range, 13.27 to 26.53 h) compared with 12.72 hours (12.00 to 14.04 h) in the SCS group (P ≤ .007) (Figure 1). In the HMP group, 58 of 74 kidneys (78%) were transplanted during elective hours (8:00 AM to 8:00 PM), significantly more than the 58 of 101 kidneys (57%) in the SCS group (P = .006).

Hypothermic machine perfusion parameters
Overall, kidneys had median 58% (interquartile range, 48% to 64%) of total CIT undergoing HMP. The median time of HMP during CIT was 14.50 hours (9.75 to 15.75 h). Perfusion pressure was constant at 30 mm Hg. Temperature remained ≤ 4°C. Changes in flow and resistance during machine perfusion mostly occurred within the first 60 minutes (Figure 2). Overall, flow increased from median 53 mL/min (interquartile range, 39.50 to 76.00 mL/min) to 100 mL/min (81.00 to 128.50 mL/min). Resistance decreased from median 0.48 mm Hg/mL/min (0.33 to 0.66 mm Hg/mL/min) to 0.22 mm Hg/mL/min (0.18 to 0.29 mm Hg/mL/min).

Repeated measures analysis of variance showed that, although the change in resistance over time was significant (P < .001), reflecting the large decline in resistance during the first hour, there was no significant difference in resistance between kidneys with immediate graft function or DGF (P = .827). The interaction term in the model was not significant (P = .841), and there was no evidence that the effect of resistance over time was related to DGF (Figure 3).

Complications and length of stay
There was 1 recipient death in the HMP group due to a cardiac event. There were 2 of 175 patients who developed primary nonfunction (PNF), 1 of which had the graft removed; these were both in the SCS group. There were 10 patients overall who had graft loss (HMP, 5 patients; SCS, 5 patients), caused by vessel thrombosis (n = 7), renal vein tear (n = 1), PNF (n = 1), and graft failure of unknown cause (n = 1). Other inpatient complications most commonly included respiratory infection, diarrhea/ileus, and bleeding (Table 2). Median inpatient length of stay was 9 days in both groups (interquartile range: HMP, 7 to 12 d; SCS, 8 to 14 d; P = .310).

Postoperative creatinine
Geometric mean creatinine levels for HMP kidneys at 3, 6 and 12 months were 134 μmol/L, 144 μmol/L, and 154 μmol/L, compared with 136 μmol/L, 136 μmol/L, and 138 μmol/L in the SCS group (Figure 4). Repeated measures analysis of variance showed that that these values did not differ between the groups (P = .717) or over time (P = .594), and the absence of significance over time was common to both groups (interaction: P = .489).

Discussion

Deceased-donor renal transplant is a process with many variables relating to the donor kidney, recipient, and hospital environment. Although CIT traditionally has been regarded as the most impor-tant factor affecting posttransplant outcome, the growing complexity of deceased-donor transplant mandates that other factors should be given equal consideration.

Growing transplant waiting lists have driven the increased use of ECD and DCD organs, despite their greater risk of poor initial graft function than standard criteria donor kidneys.^9-12 Similarly, recipients have become more complex, with living-donor transplant selecting patients with less comorbid conditions and patients who receive preemptive grafts or have shorter periods of time on dialysis. The higher-risk patients typically remain on the deceased-donor waiting list.

It can be challenging to ensure that complex recipients of deceased-donor kidneys are suitable for surgery. These recipients often require reevaluation and additional preparation on admission to ensure safe surgery. The combined responsibility of attending to increasingly intricate kidney and recipient factors may prolong CIT, and may extend into out-of-hours operating time. This compounds an already apparent paradox; living-donor recipients, with lower levels of comorbidity, are transplanted on elective lists with the highest level of expertise, whereas more complex deceased-donor recipients are treated outside normal working hours by emergency teams with variable experience in the anesthetic and operative treatment of complex renal failure patients. The National Confidential Enquiry into Perioperative Deaths reports have demonstrated that patients undergoing surgery under the latter circumstances experience a less favorable out-come.^17,18

Accordingly, it would appear evident that, to achieve the highest standards of care, either the level of expertise in out-of-hours surgery must be upgraded to equal that provided for living-donor recipients, or deceased-donor renal transplant must become an in-hours procedure. The former is difficult; providing the highest level of expertise around the clock, 365 days/year poses a problem due to the finite limitations on human and financial resources. Moving renal transplant into elective hours would reconcile some of the logistic issues but would only be acceptable if CIT could be prolonged without detriment to the kidney.

In this study, a dedicated renal transplant theater and team were available from 8:00 AM to 8:00 PM. However, ensuring that surgery proceeded on this list would prolong CIT. To address this, HMP was used to bridge longer CIT in the anticipation that this would minimize the effect of CIT on graft function.The HMP is an increasingly recognized alternative form of kidney preservation to SCS. During HMP, cold preservation solution is pumped continuously through the renal vasculature during storage.¹⁹ Improved graft outcomes have been achieved using HMP, but the exact mechanism by which this occurs remains unclear. Studies have reported both reduced DGF and improved graft survival using HMP to preserve deceased-donor kidneys.^20-29

Others studies have suggested that HMP may permit longer CIT without increasing DGF rates.^23,30 The present study supports this concept. Despite the significantly longer CITs in the HMP group, less DGF was experienced than in kidneys stored for shorter periods using SCS. The reduction in DGF was statistically significant overall and for DBD kidneys only. In the DCD group, CITs were significantly longer but the reduction in DGF failed to reach statistical significance. However, the DCD numbers were small.

The overall rate of DGF in our study population was 38%. Comparing rates of DGF across different studies is difficult due to inconsistencies in the definition of DGF and differences in donor demo-
graphics. Rates have been reported from 2% to 50%.31 The DGF rates in our study may initially appear high. However, patients receiving dialysis for any reason postoperatively were included, and there were significant numbers of ECD and DCD kidneys that have a higher risk of DGF.

The study also demonstrated that longer storage periods can be used to resolve assessment and logistic issues, permitting more transplants to be performed during daytime hours. The reduced number of cardiorespiratory problems in the HMP group may reflect the specialist anesthetic and recovery care available during elective hours, although these numbers were small. The effects of HMP during organ storage, increased time for preparation, and improved perioperative conditions may have all contributed to the improved outcomes.Creatinine levels following transplant were similar in both groups. Longer-term follow-up of graft function in the 2 groups is necessary; however, if 1-year creatinine level is accepted as a surrogate marker of future outcome, then HMP-treated kidneys would appear to have similar potential as SCS kidneys, despite longer CITs at transplant.

Kidneys showing the best functional outcome during HMP typically have reduced intrarenal resistance during the perfusion process, implying that the machine process improves renal microvascular circulation.³² Several studies have cautioned about the dangers of using resistance values to determine whether a kidney should be discarded; although resistance has been demonstrated as an independent predictor of DGF, its predictive value is poor.^33-36 In this study, there was no significant difference in resistance or change in resistance between the kidneys with DGF or immediate graft function, and no kidneys were discarded based on these measurements.

A limitation of this study was the small sample size and low number of DCD kidneys. The increased number of DCD kidneys in the SCS group may have caused a bias to transplant DCD kidneys more expeditiously, despite some studies that have suggested that this group most likely may benefit most from HMP.^20,37 The increased number of DCD donors in the SCS group may bias the results in favor of HMP; however, if DBD kidneys alone are analyzed, then the beneficial results of HMP on graft function still are significant.

In the United Kingdom, deceased-donor kidneys usually arrive at the transplant center in SCS.

Consequently, in this study and according to departmental guidelines, the decision was made to take kidneys from SCS and place them on HMP. This decision was based upon the prediction of CIT, which was based on a consideration of other logistic factors. Therefore, allocation of storage type was not randomized. Although this introduced a selection bias, the purpose of this study was not to prove the superiority of HMP over SCS; this has been demonstrated in larger multicenter trials.²⁰ Our aim was to investigate how HMP could be implemented to improve our current practice.

Dedicated perfusion therapists were not required to place and monitor kidneys on HMP. At this time, our unit has a renal surgery registrar on call 24 hours/day. Support and training was provided by the manufacturer (Organ Recovery Systems). The transporter (LifePort Kidney Transporter 1.0) was very simple to use and not as labor intensive as warm perfusion systems. Transplant centers with less support staff might find implementing such a system more difficult.

There is an initial cost associated with purchasing the HMP machine and disposable equipment. This has led some workers to question the cost effec-tiveness of HMP compared with SCS.³⁸ However, with evidence of reduced DGF rates and a subsequent reduction in dialysis requirements and hospital stay, HMP use could offset perfusion cost.³²

In this study, despite unit guidelines, not all HMP kidneys were transplanted during elective hours as planned, and several SCS kidneys also were transplanted out of hours. These breaches of guidelines were most often due to predicted theater times becoming unavailable due to delays with recipient preparation, theater team unavailability, or previously unexpected competing emergency cases. The complex logistics associated with offers of multiple kidneys occasionally resulted in HMP kidneys, originally designated to elective lists, to be transplanted in emergency theater time. Such unpredictability is inherent to a busy hospital and largely unavoidable. It could be argued that if all kidneys had been placed on HMP upon arrival to the unit, they would have been preemptively protected against most reasonable eventualities. Furthermore, since evidence suggests that the effect of HMP on DGF is heightened when perfusion is commenced immediately after procurement it would seem even more reasonable to commence all deceased-donor kidneys on HMP at source rather than at the implanting unit.^20,39 This would maximize the benefit of HMP on DGF and permit a reasonable prolon-gation of CIT, allowing for improved assessment of recipients and more flexible operating logistics to ensure the highest level of available expertise.

Traditional concerns about CIT have dictated that surgery be expedited, perhaps at the cost of other factors. However, these patients require careful assessment and sometimes intervention on the day of transplant. This study demonstrates that com-parable outcomes can be achieved with longer CITs by using HMP storage rather than traditional SCS. This effect is likely multifactorial including the inherent effects of HMP, improved recipient preparation, and possibly better perioperative conditions. Additional larger studies of subgroups and long-term outcomes would be beneficial in further defining the utility of HMP.

References:

1. Peters TG, Shaver TR, Ames JE 4th, Santiago-Delpin EA, Jones KW, Blanton JW. Cold ischemia and outcome in 17,937 cadaveric kidney transplants. Transplantation. 1995;59(2):191-196.
   CrossRef - PubMed
2. Ojo AO, Wolfe RA, Held PJ, Port FK, Schmouder RL. Delayed graft function: risk factors and implications for renal allograft survival. Transplantation. 1997;63(7):968-974.
   CrossRef - PubMed
3. Koning OH, Ploeg RJ, van Bockel JH, et al. Risk factors for delayed graft function in cadaveric kidney transplantation: a prospective study of renal function and graft survival after preservation with University of Wisconsin solution in multi-organ donors. European Multicenter Study Group. Transplantation. 1997;63(11):1620-1628.
   CrossRef - PubMed
4. Lee CM, Carter JT, Randall HB, et al. The effect of age and prolonged cold ischemia times on the national allocation of cadaveric renal allografts. J Surg Res. 2000;91(1):83-88.
   CrossRef - PubMed
5. Irish WD, McCollum DA, Tesi RJ, et al. Nomogram for predicting the likelihood of delayed graft function in adult cadaveric renal transplant recipients. J Am Soc Nephrol. 2003;14(11):2967-2974.
   CrossRef - PubMed
6. Cohen B, D'Amaro J, De Meester J, Persijn GG. Changing patterns in organ donation in Eurotransplant, 1990-1994. Transpl Int. 1997;10(1):1-6.
   CrossRef - PubMed
7. Cohen B, Smits JM, Haase B, Persijn G, Vanrenterghem Y, Frei U. Expanding the donor pool to increase renal transplantation. Nephrol Dial Transplant. 2005;20(1):34-41.
   CrossRef - PubMed
8. Audard V, Matignon M, Dahan K, Lang P, Grimbert P. Renal transplantation from extended criteria cadaveric donors: problems and perspectives overview. Transpl Int. 2008;21(1):11-17.
   PubMed
9. Metzger RA, Delmonico FL, Feng S, Port FK, Wynn JJ, Merion RM. Expanded criteria donors for kidney transplantation. Am J Transplant. 2003;3(suppl 4):114-125.
   CrossRef - PubMed
10. Ojo AO, Hanson JA, Meier-Kriesche H, et al. Survival in recipients of marginal cadaveric donor kidneys compared with other recipients and wait-listed transplant candidates. J Am Soc Nephrol. 2001;12(3):589-597.
    PubMed
11. Port FK, Bragg-Gresham JL, Metzger RA, et al. Donor characteristics associated with reduced graft survival: an approach to expanding the pool of kidney donors. Transplantation. 2002;74(9):1281-1286.
    CrossRef - PubMed
12. Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients (OPTN/SRTR), 2006. 2006 OPTN/SRTR Annual Report. The U.S. Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients Web site. http://optn.transplant.hrsa.gov. Accessed March 6, 2007.
13. Forsythe JL. Transplantation: Companion to Specialist Surgical Practice. Edinburgh: Elsevier Health Sciences; 2013.
14. Danovitch GM, Hariharan S, Pirsch JD, et al. Management of the waiting list for cadaveric kidney transplants: report of a survey and recommendations by the Clinical Practice Guidelines Committee of the American Society of Transplantation. J Am Soc Nephrol. 2002;13(2):528-535.
    PubMed
15. Shaw TM, Lonze BE, Feyssa EL, et al. Operative start times and complications after kidney transplantation. Clin Transplant. 2012;26(3):E177-E183.
    CrossRef - PubMed
16. Seow YY, Riad H, Dyer P. Impact of changing trend in cold ischaemic time on operating times in renal transplantation. Ann R Coll Surg Engl. 2006;88(7):667-671.
    CrossRef - PubMed
17. Campling EA, Devlin H, Hoile R. Who Operates When? A Report by the National Confidential Enquiry into Perioperative Deaths (1 April 1995 to 31 March 1996). London: National Confidential Enquiry into Perioperative Deaths; 1997.
18. Cullinane M, Gray AJG, Hargreaves CMK, Lansdown M, Martin IC, SchubertM. Who Operates When? II: The 2003 Report by the National Confidential Enquiry into Perioperative Deaths. London: National Confidential Enquiry into Perioperative Deaths; 2003.
19. St. Peter SD, Imber CJ, Friend PJ. Liver and kidney preservation by perfusion. Lancet. 2002;359(9306):604-613.
    CrossRef - PubMed
20. Moers C, Smits JM, Maathuis MH, et al. Machine perfusion or cold storage in deceased-donor kidney transplantation. N Engl J Med. 2009;360(1):7-19.
    CrossRef - PubMed
21. Moers C, Pirenne J, Paul A, Ploeg R, Machine Preservation Trial Study Group. Correspondence: Machine perfusion or cold storage in deceased-donor kidney transplantation. N Engl J Med. 2012;366(8):770-771.
    CrossRef - PubMed
22. Lodhi SA, Lamb KE, Uddin I, Meier-Kriesche HU. Pulsatile pump decreases risk of delayed graft function in kidneys donated after cardiac death. Am J Transplant. 2012;12(10):2774-2780.
    CrossRef - PubMed
23. Schold JD, Kaplan B, Howard RJ, Reed AI, Foley DP, Meier-Kriesche HU. Are we frozen in time? Analysis of the utilization and efficacy of pulsatile perfusion in renal transplantation. Am J Transplant. 2005;5(7):1681-1688.
    CrossRef - PubMed
24. Wight JP, Chilcott JB, Holmes MW, Brewer N. Pulsatile machine perfusion vs. cold storage of kidneys for transplantation: a rapid and systematic review. Clin Transplant. 2003;17(4):293-307.
    CrossRef - PubMed
25. Kwiatkowski A, Wszola M, Kosieradzki M, et al. Machine perfusion preservation improves renal allograft survival. Am J Transplant. 2007;7(8):1942-1947.
    CrossRef - PubMed
26. Matsuoka L, Shah T, Aswad S, et al. Pulsatile perfusion reduces the incidence of delayed graft function in expanded criteria donor kidney transplantation. Am J Transplant. 2006;6(6):1473-1478.
    CrossRef - PubMed
27. Stratta RJ, Moore PS, Farney AC, et al. Influence of pulsatile perfusion preservation on outcomes in kidney transplantation from expanded criteria donors. J Am Coll Surg. 2007;204(5):873-884.
    CrossRef - PubMed
28. Shah AP, Milgrom DP, Mangus RS, Powelson JA, Goggins WC, Milgrom ML. Comparison of pulsatile perfusion and cold storage for paired kidney allografts. Transplantation. 2008;86(7):1006-1009.
    CrossRef - PubMed
29. Cannon RM, Brock GN, Garrison RN, Smith JW, Marvin MR, Franklin GA. To pump or not to pump: a comparison of machine perfusion vs cold storage for deceased donor kidney transplantation. J Am Coll Surg. 2013;216(4):625-634.
    CrossRef - PubMed
30. Ciancio G, Gaynor JJ, Sageshima J, et al. Favorable outcomes with machine perfusion and longer pump times in kidney transplantation: a single-center, observational study. Transplantation. 2010;90(8):882-890.
    CrossRef - PubMed
31. Perico N, Cattaneo D, Sayegh MH, Remuzzi G. Delayed graft function in kidney transplantation. Lancet. 2004;364(9447):1814-1827.
    CrossRef - PubMed
32. Wight J, Chilcott J, Holmes M, Brewer N. The clinical and cost-effectiveness of pulsatile machine perfusion versus cold storage of kidneys for transplantation retrieved from heart-beating and non-heart-beating donors. Health Technol Assess. 2003;7(25):1-94.
    CrossRef - PubMed
33. Jochmans I, Pirenne J. Graft quality assessment in kidney transplantation: not an exact science yet! Curr Opin Organ Transplant. 2011;16(2):174-179.
    CrossRef - PubMed
34. Jochmans I, Moers C, Smits JM, et al. The prognostic value of renal resistance during hypothermic machine perfusion of deceased donor kidneys. Am J Transpl. 2011;11(10):2214-2220.
    CrossRef - PubMed
35. de Vries EE, Hoogland ER, Winkens B, Snoeijs MG, van Heurn LW. Renovascular resistance of machine-perfused DCD kidneys is associated with primary nonfunction. Am J Transpl. 2011;11(12):2685-2691.
    CrossRef - PubMed
36. Sonnenday CJ, Cooper M, Kraus E, Gage F, Handley C, Montgomery RA. The hazards of basing acceptance of cadaveric renal allografts on pulsatile perfusion parameters alone. Transplantation. 2003;75(12):2029-2033.
    CrossRef - PubMed
37. Jochmans I, Moers C, Smits JM, et al. Machine perfusion versus cold storage for the preservation of kidneys donated after cardiac death: a multicenter, randomized, controlled trial. Ann Surg. 2010;252(5):756-764.
    CrossRef - PubMed
38. Bond M, Pitt M, Akoh J, Moxham T, Hoyle M, Anderson R. The effectiveness and cost-effectiveness of methods of storing donated kidneys from deceased donors: a systematic review and economic model. Health Technol Assess. 2009;13(38):iii-iv, xi-xiv, 1-156.
    CrossRef - PubMed
39. Watson CJ, Wells AC, Roberts RJ, et al. Cold machine perfusion versus static cold storage of kidneys donated after cardiac death: a UK multicenter randomized controlled trial. Am J Transplant. 2010;10(9):1991-1999.
    CrossRef - PubMed