Is Machine Perfusion a Superior Method of Preserving Donor Kidneys?

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Is Machine Perfusion a Superior Method of Preserving Donor Kidneys?

Posted 02/06/2009

Robert J. Stratta, MD
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Machine Perfusion or Cold Storage in Deceased-Donor Kidney Transplantation

Moers C, Smits JM, Maathuis MH, et al
N Engl J Med. 2009;360:7-19
Summary

From November 1, 2005 through October 31, 2006, the authors performed an international (European), prospective, controlled trial of randomly assigning 1 kidney from 336 consecutive deceased donors to either machine perfusion or static cold storage preservation. Of 654 potential consecutive donors, 318 were excluded for a variety of reasons during the study period. In 25 donors (4.6%), preservation methods were switched because of aberrant vascular anatomy of the kidney assigned to machine perfusion.

Organ donors were 16 years of age or older and consisted of either donation after brain death (DBD, n = 294, 87.5%) or Maastricht category III donation after cardiac death (DCD, n = 42, 12.5%) donors. The LifePort® Kidney Transporter device (Organ Recovery Systems) was used for machine perfusion. Flow and resistance readings were not revealed to the transplant team to prevent bias in clinical decisions regarding organ discard. Kidney pairs were included only if both kidneys were actually transplanted as kidney-only transplants into 2 different recipients, and both recipients survived at least 1 week after transplantation.

There were no significant differences between the 2 groups regarding relevant baseline characteristics; mean cold ischemia times were 15.0 hours in each group. The incidence of delayed graft function (DGF), defined as the need for dialysis in the first week posttransplant, was 20.8% with machine perfusion compared to 26.5% with cold storage preservation (adjusted odds ratio = 0.57, P = .01). The incidence of functional DGF, defined as the absence of a decrease in the serum creatinine level of at least 10% per day for 3 consecutive days in the first week posttransplant, was 22.9% with machine perfusion compared to 30.1% with cold storage preservation (P = .03). The comparative incidence of primary nonfunction (2.1% machine perfusion vs 4.8% cold storage, P = .08) did not reach statistical significance but was perhaps clinically significant because of a > 50% reduction in primary nonfunction associated with machine perfusion.

If DGF developed, its duration was a mean of 3 days shorter with machine perfusion (10 days vs 13 days with cold storage, P = .04). The magnitude of the above effects was similar for DBD, DCD, and expanded criteria donors (ECD). Daily serum creatinine levels in the first 2 weeks posttransplant were significantly lower in the machine perfusion group, but 2-week creatinine clearance values were no different according to method of preservation.

The 1-year kidney graft survival rate was significantly greater in the machine perfusion group (94% vs 90% with cold storage, P = .04). Cox regression analysis revealed that in the first year after transplantation, machine perfusion significantly reduced the risk for graft failure (hazard ratio 0.52, P = .03) whereas the presence of DGF increased the risk for graft failure (hazard ratio 1.69, P < .001). No differences were noted in patient survival, length of hospital stay, acute rejection, or calcineurin inhibitor toxicity between the 2 groups.

Based on these findings, the authors concluded that machine perfusion appears to be a superior method of preservation regardless of deceased donor category, based on a lower incidence and shorter duration of DGF and improved 1-year graft survival when compared to static cold storage.
Viewpoint

The presence of DGF is an early surrogate marker of organ quality and preservation and is a manifestation of ischemia-reperfusion injury. DGF is a form of acute renal failure following kidney transplantation that results in oliguria, enhanced allograft immunogenicity, and decreased long-term graft survival.

The incidence of DGF has not changed appreciably in the past decade and typically occurs in 20% to 30% of DBD deceased donor kidney transplants. The incidence is highest in DCD, intermediate in ECD, lower in standard criteria donor , and lowest in living donor kidney transplant recipients. The major risk factors for DGF appear to be warm and cold ischemia, which account for the hierarchy of DGF among the various donor categories. It is estimated that after 12 hours of static cold storage preservation, the rate of DGF increases by 5% for each 6 additional hours of cold ischemia. Consequently, after 24 hours of cold ischemia, the rate of DGF is doubled compared to 12 hours of static cold storage preservation.

Once a deceased donor kidney is recovered, there are 2 methods of preservation: simple or static cold hypothermic storage and pulsatile machine perfusion preservation. Static cold storage preservation relies on customized solutions that contain specialized additives such as impermeants, buffers, antioxidants, and energy precursors to counteract cell swelling and minimize apoptosis. In contrast, machine perfusion involves an ex vivo, hypothermic pulsatile perfusion pump that delivers oxygen and nutrients through a specialized preservation solution to the kidney while removing waste products in an attempt to mimic the circulation, thereby preserving endothelial and parenchymal integrity and reducing vasospasm. Machine perfusion was initially developed in the 1960s by Belzer and colleagues as a more physiologic method of renal preservation. In the 1980s, with the introduction of a new hypothermic machine preservation solution, machine perfusion was touted as a superior method of organ preservation and cold ischemia times were extended to 30-40 hours and beyond without compromise in graft outcomes and attended by remarkably low rates of DGF (< 10%).

There have been numerous previous studies directly comparing static cold storage to machine perfusion preservation, particularly with standard criteria DBD donor kidneys with cold ischemia times of 24 hours or less, which suggest that neither preservation technique was associated with a clinical advantage. However, recent reports have suggested that machine perfusion may lower the risk for DGF in ECD kidneys.

The above report by Moers and colleagues represents a landmark study because it demonstrates the superiority of machine perfusion as a method of preservation in all deceased donor categories with preservation times less than 24 hours. Moreover, the paired donor kidney study design eliminates donor factors as an explanation for the subsequent differences in clinical outcomes that occurred following transplantation. It is well established that prevention of DGF may have beneficial short- and long-term consequences, and the results of this study demonstrate a significant decline in graft loss at 1 year for kidneys preserved by machine perfusion. Whether this improvement in short-term graft survival will translate into a long-term benefit is unknown.

Ultimately, understanding the factors that mitigate ischemia-reperfusion injury and longer-term follow-up are necessary to fully delineate the benefits of, and risks for, various preservation techniques in deceased donor kidney transplantation.

http://www.medscape.com/viewarticle/587500