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Keywords:

  • Cardiac death donors;
  • machine preservation;
  • kidney preservation;
  • kidney transplantation

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Statement of Authors' Contributions
  8. Acknowledgments
  9. Sources of Funding
  10. Conflicts of Interest
  11. References

One third of deceased donor kidneys for transplantation in the UK are donated following cardiac death (DCD). Such kidneys have a high rate of delayed graft function (DGF) following transplantation. We conducted a multicenter, randomized controlled trial to determine whether kidney preservation using cold, pulsatile machine perfusion (MP) was superior to simple cold storage (CS) for DCD kidneys. One kidney from each DCD donor was randomly allocated to CS, the other to MP. A sequential trial design was used with the primary endpoint being DGF, defined as the necessity for dialysis within the first 7 days following transplant. The trial was stopped when data were available for 45 pairs of kidneys. There was no difference in the incidence of DGF between kidneys assigned to MP or CS (58% vs. 56%, respectively), in the context of an asystolic period of 15 min and median cold ischemic times of 13.9 h for MP and 14.3 h for CS kidneys. Renal function at 3 and 12 months was similar between groups, as was graft and patient survival. For kidneys from controlled DCD donors (with mean cold ischemic times around 14 h), MP offers no advantage over CS, which is cheaper and more straightforward.


Abbreviations: 
DBD

donation after brain death

DCD

donation after cardiac death

DD

deceased donor

DGF

delayed graft function

CCR2

creatinine reduction ratio on day 2 = (creatinine day 2 − creatinine day 1)/creatinine day 1

CCR5

creatinine reduction ratio on day 5 = (creatinine day 5 − creatinine day 0)/creatinine day 0

UW

University of Wisconsin cold storage solution (ViaSpan)

KPS-1

kidney perfusion solution − 1 (the University of Wisconsin machine perfusion solution)

Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Statement of Authors' Contributions
  8. Acknowledgments
  9. Sources of Funding
  10. Conflicts of Interest
  11. References

A majority of deceased donor (DD) kidneys for transplantation are obtained from heart-beating donors who donate after brain death (DBD). However, an increasing number of kidneys are obtained from nonheart beating donors where controlled donation after cardiac death (DCD) is performed. In the UK the number of transplants using kidneys from DCD donors has risen dramatically from only 31 in 1999 to 264 in 2008 and the rise in DCD kidneys looks set to continue as new initiatives to address the severe shortage of kidneys available for transplantation are introduced. Unlike kidneys from DBD donors, kidneys from DCD donors are subjected to a significant period (typically 10 to 45 min) of warm ischemic injury between cardiac arrest and perfusion with cold preservation solution. Whereas most (over 70%) kidneys from DBD donors function immediately, over half of kidneys from DCD donors suffer from an extended period of delayed graft function (DGF) necessitating continued dialysis until recovery occurs (1). Kidneys that fail to function immediately after transplantation appear more prone to acute rejection and poorer long-term function (2), although somewhat surprisingly the long-term survival of DBD and DCD kidneys appears broadly similar (3).

Prior to transplantation, DCD donors are traditionally stored in ice and the period of static cold storage (CS) kept to a minimum in an attempt to optimize transplant outcome. It has been suggested that the use of continuous cold pulsatile machine perfusion (MP) may be superior to CS for DCD kidneys although the evidence is inconclusive. A meta analysis of machine perfusion in 2003 identified three suitable trials for DCD kidneys of which two were underpowered and one dated from 1977, long before the introduction of modern MP technology or CS solutions (4). The data on the benefits of MP for DBD kidneys were also poor, with a paucity of properly powered studies. Subsequent to this review, a well-powered study of MP has been published, which suggests that MP is superior to CS for DBD donor kidney transplants (5). However, this study had insufficient DCD kidneys to comment fully on any effect of machine perfusion in this important subgroup.

In order to define the best preservation method for DCD kidneys, we conducted a randomized controlled trial of cold pulsatile MP versus CS to establish whether MP provided superior preservation as determined by improved early graft function.

Materials and Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Statement of Authors' Contributions
  8. Acknowledgments
  9. Sources of Funding
  10. Conflicts of Interest
  11. References

Study participants

All adult DCD donors at the five participating UK centers were eligible for the study although only controlled DCD donors, in whom further active treatment had been deemed futile and life-supporting treatment withdrawn (Maastricht category 3) (6), were entered.

The study (ISRCTN95022818) received appropriate approval from a UK Multisite Research Ethics Committee. Whereas all kidneys from DBD in the UK are allocated according to a national organ allocation scheme and commonly transported between centers, kidneys from DCD donors are not entered into the national sharing scheme and are instead nearly always transplanted at the retrieving center to minimize ischemic time. Recipients of DCD kidneys were eligible for enrollment to the study if they were aged 18 years or over, and had a negative crossmatch; recipients of a previous nonrenal organ transplant were excluded. Recruitment took place between August 2006 and October 2007.

Randomization

Upon notification of a potential DCD kidney donor at a participating center, the Duty Office at NHS Blood and Transplant randomized the donor kidneys to one of the two treatments, CS or MP. Randomization also dictated which kidney (right or left) was allocated to MP, and which kidney of the pair was to be transplanted first. The randomization sequence was generated using simple randomization based on a sequence of computer-generated random number integers from 1 to 4.

Treatments

Treatment withdrawal in the donor occurred following a decision that further treatment was futile, and comprised disconnection from the ventilator or extubation and cessation of inotropes as previously described (7). UK law prohibits premortem cannulation or heparinization.

Following certification of donor death a period of at least 5 min was observed with no intervention. Organ retrieval then proceeded with initial in situ cold perfusion of the kidneys using the University of Wisconsin (UW) cold storage solution (ViaSpan). After removal the kidney allocated to CS was immersed in UW solution and placed in crushed ice in an insulated transport box until implantation. The kidney allocated to MP was placed on the Organ Recovery Systems LifePort kidney preservation machine using kidney preservation solution 1 (KPS-1). The perfusion machines were preprogrammed to pulsatile perfusion mode, and set to flow at 30 mmHg pressure. The perfusion pressure setting was not adjusted during the preservation period, and data on resistance and flow were not used to determine whether or not a kidney should be used; all kidneys were subsequently transplanted. Where organ retrieval occurred away from the base transplant hospital the kidney randomized to MP could first undergo a period of CS during transport to the base hospital with MP being started immediately upon return. All recipients gave consent to participate in the study.

Immunosuppression at the time of transplant was the same in both treatment arms and comprised induction therapy with basiliximab (Simulect, Novartis Pharmaceuticals) and maintenance therapy with tacrolimus (Prograf, Astellas), mycophenolate sodium (Myfortic, Novartis Pharmaceuticals) and prednisolone, to start within 24 h of transplant.

Study endpoints

The primary endpoint for the study was the incidence of DGF, defined as the requirement for dialysis in the first 7 days following transplantation (8). The medical staff involved in the decision regarding the need for dialysis were not aware of the kidney preservation method used.

Secondary endpoints included primary nonfunction (defined as a graft that failed to provide 1-month dialysis-free survival excluding losses attributable to rejection or vascular thrombosis), and other measures of DGF, including creatinine reduction ratio calculated as either the change in creatinine from day 1 (the first day posttransplant) to day 2 (CCR2), or from immediately pretransplant (day 0) to day 5 (CCR5) (9,10). Other secondary endpoints included the incidence of acute rejection (biopsy-proven), patient survival (the time from transplant to death) and graft survival (the time from transplant to graft loss or return to dialysis) and graft function (glomerular filtration rate and serum creatinine).

All warm and cold ischemic times were recorded and classified according to the nomenclature of Wells et al. (11); the time period from treatment withdrawal in the donor to cardiac arrest was termed the withdrawal period.

Statistical methods

Since the primary endpoint was known 1 week after randomization, and there was an ethical requirement to minimize the number of patients in the study, a sequential design was chosen. Patients were recruited until there was sufficient evidence, based on the primary end point, to reject the null hypothesis that there was no difference in preservation treatments (12). Two previous studies of MP in DCD donor kidney transplants suggested a reduction in DGF from 78% and 85% down to 57% and 62%, respectively, although other publications have suggested a rate of 20% is possible with machine perfusion (13,14). We therefore used a triangular test with boundaries set to permit a 90% chance of detecting a change in the incidence of DGF from 80% on CS to 60% on MP, using a 5% significance level.

The design properties indicated an expected sample size of 142, with a 10% chance that more than 220 patients would be needed, if there were no treatment difference. This compares to a sample size of 209 patients for the equivalent fixed sample size study. The initial analysis took place after the recruitment of 60 patients, which we considered the minimum number of participants for the trial to have credence; further analyses took place after every subsequent 20 patients had reached the primary endpoint, since this interval was considered a satisfactory compromise between realizing the benefits of a sequential design and the logistical difficulties in monitoring the trial. The ‘Christmas tree correction’ (12) was used to adjust for the discrete monitoring, and an intention to treat analysis was used throughout. The data were analyzed using the PEST4 software program (Planning and Evaluation of Sequential Trials, University of Reading, Reading, UK).

Because of the paired nature of the design, most of the comparisons between treatments at 7 days and 3 months after transplant were undertaken using McNemar's test for categorical variables and the paired t-test for continuous variables. Comparisons based on subsets of recipients, namely time to last dialysis and creatinine reduction ratios, respectively used multiple linear regression and logistic regression adjusted for the height, weight, gender, age, ethnicity and center of the donor. At 12 months after transplant data on a small number of recipients were incomplete reducing the number of complete paired data, and so unpaired analyses were used. Survival times were compared using the log rank test. Univariate analyses were supplemented by risk-adjusted analyses based on multiple linear regression, logistic regression and Cox regression, as appropriate. Recipient age, HLA mismatch level, incidence of DGF, donor weight, height, gender and age were all adjusted for when investigating differences in the incidence of acute rejection. In addition to the above factors, recipient weight, height, gender, ethnicity, duration of dialysis pretransplant, type of dialysis, graft number, sensitization status, serum creatinine pretransplant, serum urea, serum albumin, serum calcium, use of a dopamine infusion, angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, calcium channel blocker as well as transplant center were all adjusted for when modeling differences in time to last dialysis, serum creatinine and eGFR. Adjusted p-values were broadly similar to those from the unadjusted analyses.

Role of the funding sources

Novartis Pharmaceuticals UK provided an unrestricted research grant and Organ Recovery Systems provided an unrestricted research grant in addition to discounting the costs of disposables used for MP. Neither company was involved in protocol development, study conduct, data analysis or writing and approval of the manuscript.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Statement of Authors' Contributions
  8. Acknowledgments
  9. Sources of Funding
  10. Conflicts of Interest
  11. References

As part of the sequential analysis, the first analysis of the primary endpoint (DGF) was performed after recruitment of 60 patients, at which point there was no statistical indication to stop further recruitment (Figure 1). Following analysis of data on the first 80 patients, the study was halted since there was no significant difference in the primary endpoint of DGF between the two groups. Figure 2 shows the flow diagram for the study. By the time recruitment to the study was stopped a total of 46 donors had been recruited from whom 91 kidney transplants resulted. One kidney was unusable following retrieval for anatomical reasons and discounted from subsequent analysis, as was the paired kidney, leaving 45 pairs for analysis. Details of the 90 transplant recipients and 45 donors are given in Table 1. The recipient groups were well matched for age, gender, ethnicity, type and duration of dialysis, sensitization status and HLA mismatch. Data were complete for the perioperative and 3-month time points, and for most patients at the 12-month time point.

image

Figure 1. Triangle plot of Z (a measure of treatment difference) against V (a summary of the amount of information in the data). The variable Z is a cumulative measure of the advantage of MP over CS; a positive value indicates that there is a lower incidence of DGF in patients on MP. The variable V is a measure of the amount of information about the treatment difference that is contained in Z; the more pairs are included the greater the precision with which the treatment difference can be estimated. If a plot of Z against V crosses the upper red boundary, the trial would be stopped for superiority of machine perfusion; if the lower red boundary were crossed, the trial would be stopped for inferiority of machine perfusion. Crossing the lower purple dashed boundary implies there is no significant difference between the two treatment arms under study. The green dashed boundaries are those corrected for discrete monitoring (Christmas Tree correction). The blue crosses indicate the pairs of values of Z and V obtained at each analysis time, and it can be seen that they cross the lower purple dashed boundary, implying no significant difference between treatment arms.

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image

Figure 2. Flow diagram for study group allocation.

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Table 1.  Details of the 90 kidney transplant recipients and 45 organ donors
Patient factorTransplant recipients1Organ donors (n = 45)
Machine perfusion (n = 45)Cold storage (n = 45)
  1. 1Intended treatment.

  2. 2Since any previous transplant failure.

  3. 3Defined as the presence of any defined HLA antibody specificity.

  4. 4These drugs have all been reported to affect the incidence of primary function in kidney transplantation.

Age (mean, SD)50.3 (14.2)48.6 (13.9)45.6 (14.6)
Gender31 male, 14 female33 male, 12 female29 male, 16 female
Ethnicity: proportion white91.1%84.4%97.8%
Months on dialysis pre transplant252.8 (53.8)44.4 (39.1) 
Type of dialysis
 Hemodialysis27 (60.0%)26 (57.8%) 
 Peritoneal dialysis15 (33.3%)16 (35.5%) 
 Predialysis3 (6.7%)3 (6.7%) 
No. of kidney transplants
 First graft39 (86.7%)40 (88.9%) 
 Regraft6 (13.3%)5 (11.1%) 
Sensitization status3
 Nonsensitized41 (91.1%)40 (88.9%) 
 Sensitized4 (8.9%)5 (11.1%) 
HLA mismatch (mean)
 HLA-A1.21.3 
 HLA-B1.21.0 
 HLA-DR0.70.7 
 Total number of HLA mismatches3.03.0 
Perioperative medications4
Dopamine infusion1 (2%)2 (4%) 
ACE inhibitor1 (2%)3 (7%) 
Angiotensin receptor blocker1 (2%)3 (7%) 
Calcium channel blocker10 (22%)17 (38%) 

The age of the organ donors ranged from 19 to 70 years (mean 45.6 years), and 16 (36%) met the UNOS extended criteria as suboptimal grafts (15,16).

Treatment allocation

Following randomization, 41 of the kidneys allocated to MP received the allocated treatment. Of the four that did not, one did not undergo MP due to a technical problem with the renal artery, one because of an error setting up MP, one was wrongly allocated, like its partner, to CS and in one case the reason was unknown.

The mean duration of MP was 10.1 h (range 2.5 h to 23.3 h) of the mean 14.0 h cold ischemia, which represented a mean of 69% (range 27–97%) of the cold ischemic period. There was no relationship between the proportion of the cold ischemic period the kidneys underwent MP and the incidence of DGF (Figure 3). Data were not recorded to allow separate analysis of the incidence of DGF in kidneys that were first placed in CS before being transferred to MP on return to base.

image

Figure 3. Graft function in relation to the proportion of the cold ischemic period that kidneys in the MP group were undergoing MP. The horizontal bar represents the mean value. There is no difference in the proportion of time on MP between kidneys with delayed graft function and those without.

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Of the 45 kidneys randomized to CS two did not receive the allocated treatment; one underwent MP in error, and one because of the supervising clinician's preference. The data were analyzed according to the intended treatment, but repeat analysis according to the actual treatment revealed similar results.

Early graft function

The results of the sequential analysis are depicted in Figure 1, which shows the trial boundaries, and the three points corresponding to the first 60 patients, the 80 patients that led to the decision to stop the trial, and the complete data from the 90 patients.

There was no difference in the incidence of DGF (the primary endpoint) between the two study groups on an intention-to-treat analysis. Of the 45 recipients of kidneys assigned to CS, 25 (56%) required dialysis posttransplant and of the 45 recipients of kidneys assigned to MP, 26 (58%) required dialysis (p = 0.99, see Table 2). The corresponding ratio of the odds of DGF in MP relative to CS, from Table 2, is 1.143 (95% CI: 0.38—3.49). Of all the recipients only one (in the CS group) required a single posttransplant dialysis within the first 24 h to treat hyperkalemia and their exclusion from the analysis resulted in a DGF rate of 53.3% which was not significantly different from that in the MP group (57.8%, p = 0.8). There was no difference between groups in the other surrogates of DGF including CCR2 or CCR5, the day 7 estimated GFR (MDRD equation (17)), or duration of dialysis requirement (see Table 3).

Table 2.  Incidence of delayed graft function (requirement for dialysis in the first 7 days)
  Machine perfusion
No DGFDGFTotal
  1. The table shows for each pair of kidneys from a given donor whether both kidneys behaved the same following preservation (i.e. both recipients experienced DGF or did not experience DGF) or whether the recipient of one kidney of the pair had immediate function while the other had DGF. Hence in 12 pairs neither kidney recipient had DGF, and in 8 cases the cold stored kidney recipient did not have DGF while the recipient of the machine preserved kidney did experience DGF.

Cold storageNo DGF12 820
DGF 71825
Total 192645
Table 3.  Outcomes of grafts based on intention to treat by static cold storage and machine perfusion
 Machine perfusion n = 45*Cold storage n = 45*p
  1. *n = 45 unless stated otherwise; 95% confidence intervals provided unless stated otherwise.

  2. Two kidneys never worked; one was allocated to receive machine perfusion but was actually cold stored and was lost due to venous thrombosis on day 1.

  3. Not adjusted for potential confounding variables, although the results are broadly similar after adjustment.

Asystolic period (mean, range) (= first warm time)15 minutes (4–35) 
Cold ischemic period (mean, range)13.9 h (6.7 to 24.2, n = 44)14.3 h (7.0 to 30.1, n = 44)0.77
Anastomosis period (mean, range) (= second warm time)44 minutes (18 to 85, n = 44)42 minutes (20 to 73, n = 44)0.4
Total ischemic period (mean, range)14.9 h (7.6 – 25.3) (n = 44)15.2 h (7.6–31.0) (n = 44)0.8
Primary nonfunction10 
Dialysis requirement
First 7 days (DGF)26 (57.8%)25 (55.6%)0.99
Day 2 to 726 (57.8%)24 (53.3%)0.80
Median duration of dialysis (only those requiring it)5 days (1 to 92) (n = 26)7 days (1 to 33) (n = 25)0.4
CRR2 <30% (excludes patients requiring dialysis on day 1)26/3429/340.48
CRR5 <30%33/4531/450.6
CCR5 mean9.2% (−70 to 81)7.5% (−71 to 82)0.86
eGFR (mL/min/1.73m2) mean
 At day 717.0 (4 to 50)14.9 (4 to 46)0.24
 At 3 months46.0 (17 to 73)48.9 (16 to 79)0.42
 At 12 months46.6 (15–84) (n = 38)46.2 (7–81) (n = 38)0.64
Rejection-free survival (95% CI)
 At 3 months93% (80–98)78% (63–87)0.06
 At 1 year91% (77–96)78% (63–87)0.1
Graft survival at 1 year (95% CI)93.3% (80–98)98% (85–100)0.3
Patient survival at 1 year (95% CI)93% (81–98)100%0.08

One kidney suffered primary nonfunction and another had a venous thrombosis on day 1. Both were allocated to MP although the kidney with thrombosis underwent CS. In both cases, the pair kidney functioned satisfactorily, although DGF occurred in one of these.

Acute rejection

Three patients (7%) allocated to MP developed acute rejection in the first 3 months, compared to 10 (22%) in the CS group (p = 0.06); one kidney with rejection allocated to MP underwent CS. The acute rejection rate at 1 year was 9% in the MP group and 22% in the CS group (p = 0.1). Of the 51 recipients with DGF, 10 (20%) had an acute rejection episode within 3 months compared to 3/39 (8%) recipients without DGF (p = 0.11).

Graft and patient outcomes

Graft function, as determined by eGFR, was similar in both groups at 3 and 12 months following transplantation. One year following transplantation three kidneys had failed in the MP arm and one in the CS arm, giving graft survival rates of 93.3% and 97.8%, respectively (p = 0.3). One of the three failed kidneys allocated to MP received CS.

Three patients died in the MP arm and none in the cold storage arm, giving 1-year patient survival rates of 93.3% and 100%, respectively (p = 0.08). MP was also the actual treatment for these three patients. Two of the three patients had functioning grafts at the time of death and the third patient's graft failed due to rejection.

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Statement of Authors' Contributions
  8. Acknowledgments
  9. Sources of Funding
  10. Conflicts of Interest
  11. References

The results of this multicenter randomized controlled trial demonstrate that cold pulsatile machine perfusion provides no benefit over simple cold storage for kidneys donated after cardiac death. MP did not reduce the incidence of DGF, the primary end point of the study, nor did it improve graft function up to 12 months following transplantation. The study is the largest randomized controlled trial to date to specifically address MP of kidneys from controlled (Maastricht category 3) DCD donors. The sequential design of this study deserves comment as we believe it is the first time such an approach has been used in a controlled trial of organ transplantation, although the methodology is well proven in other clinical contexts (18–20). This study lent itself particularly well to a sequential design given the uncertainty about the likely DGF rate and the fact that the primary endpoint occurred soon after randomization. When further recruitment to the study was stopped after 46 donors it was clear that the MP would not show superiority if recruitment continued: for example, if recruitment had been extended to include a further 16 donors, all of the kidneys assigned to MP would need primary function, and all the kidneys assigned to CS develop DGF for MP to be significantly superior to CS.

The findings of this study are in marked contrast to those recently reported from a large European multicenter randomized controlled trial of MP in kidneys from both DBD and DCD donors (5). The European study showed that MP reduced DGF compared to CS, although it is important to note that the majority of recipients received kidneys that were from DBD rather than DCD donors. Differences in the nature of the ischemic injury incurred prior to procurement could, in principle, explain why MP is superior to CS for kidneys from DBD but not DCD donors. Kidneys from DCD donors may not be exposed to the severe hormonal disturbances that accompany brain death (21), but instead incur a significant period of warm ischemic injury between cessation of heart beat and in situ cold perfusion, as well as a variable period of relative ischemia when, following withdrawal of inotropes and ventilatory support, the donor heart slowly fails (7). However, such differences may not explain the differing findings between this study and the European study: a recently reported extension to the European study of 82 DCD donors showed that MP reduced DGF from 70% to 54% (22).

It is notable that the DGF rate for DCD kidneys subjected to CS was lower in this study than in the European DCD extension study (DGF 56% vs. 70%) but that the DGF rates after MP were similar in the UK (58%) and European (54%) studies. A possible interpretation is that, although the mean cold ischemia times were similar in the two studies, kidneys in the European study may have incurred more warm ischemic injury before procurement. This might be reflected by a higher DGF rate, and it may be that MP in this context is of greater benefit. There are, however, other relevant differences between the two studies. In this study, immunosuppression was standardized for all centers as was the use of UW solution for CS. In the European MP study immunosuppression was not standardized and investigators were able to choose between UW solution and Histidine-Tryptophan-Ketoglutarate (HTK) solution for CS (5). Another difference between the two studies is that in the European study kidneys randomized to MP were placed on a perfusion machine at the donor center, whereas in this study those kidneys not removed at the transplanting center were transferred back to the transplant center before MP was commenced. The proportion of the cold ischemic period that a kidney was undergoing MP is likely to have been less in this study than in the European study, and use of MP throughout the cold ischemic period may be necessary to achieve a benefit.

One further observation in our study was the reduced incidence of acute rejection in the MP arm at 3 months (7% vs. 22%, p = 0.06), an effect that was lost at 12 months (9% vs. 22%, p = 0.1). It is not clear why machine perfusion might result in lower incidence of acute rejection. It is possible the observation occurred by chance since the study was not powered to look at differences in rejection incidence. It is noteworthy that no such effect was noted for acute rejection at 14 days in the European study (5).

In conclusion, the results of this study show that for kidneys from controlled DCD donors, with mean total ischemic times of 15 h, MP offers no advantage over static cold storage that is a cheaper and more straightforward alternative.

Statement of Authors' Contributions

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Statement of Authors' Contributions
  8. Acknowledgments
  9. Sources of Funding
  10. Conflicts of Interest
  11. References

Chris Watson conceived of the study, developed the protocol, secured the funding and contributed to writing the manuscript. Antonia Wells and Rebecca Roberts were involved in coordinating the study, collecting the data and writing the paper. Jacob Akoh, Murat Akyol, Francis Calder and Peter Friend were involved in refining the protocol, contributing patients to the study, and writing the manuscript. Joanne Allen, Mark Jones and Dave Collett analyzed the data, and Andrew Bradley and Dave Collett contributed to the study design, protocol development and writing the manuscript.

Acknowledgments

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Statement of Authors' Contributions
  8. Acknowledgments
  9. Sources of Funding
  10. Conflicts of Interest
  11. References

The authors are extremely grateful to all the clinicians and nurses in the participating centers for their help, and in particular to Andrew Broderick (Plymouth), Liz Waite (Edinburgh), Mary Simmonds (Oxford) and Nizam Mamode (Guys).

In addition, we are grateful to George Stanley, Derek Wallace and Marcus Arden Jones of Novartis Pharmaceuticals UK, and to Luanne Rodgers of Organ Recovery Systems for their help in setting up and running the study. We are also grateful to the Duty Office of NHS Blood and Transplant for providing the randomization service.

The study was approved by the British Transplantation Society's Clinical Trials Subcommittee.

Sources of Funding

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Statement of Authors' Contributions
  8. Acknowledgments
  9. Sources of Funding
  10. Conflicts of Interest
  11. References

The Research described was funded by a large unrestricted research grant from Novartis Pharmaceuticals UK and a smaller grant from Organ Recovery Systems.

Conflicts of Interest

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Statement of Authors' Contributions
  8. Acknowledgments
  9. Sources of Funding
  10. Conflicts of Interest
  11. References

Mr. Watson has received honoraria for attendance at Advisory Boards for Organ Recovery Systems and Novartis, and Novartis covered the costs of travel to and attendance at the American Transplant Congress in 2008. Ms. Wells has received honoraria for attendance at Advisory Boards for Organ Recovery Systems.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Statement of Authors' Contributions
  8. Acknowledgments
  9. Sources of Funding
  10. Conflicts of Interest
  11. References