Machine Perfusion or Cold Storage in Deceased-Donor Kidney Transplantation

Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
New England Journal of Medicine (Impact Factor: 54.42). 02/2009; 360(1):7-19. DOI: 10.1056/NEJMoa0802289
Source: PubMed

ABSTRACT Static cold storage is generally used to preserve kidney allografts from deceased donors. Hypothermic machine perfusion may improve outcomes after transplantation, but few sufficiently powered prospective studies have addressed this possibility.
In this international randomized, controlled trial, we randomly assigned one kidney from 336 consecutive deceased donors to machine perfusion and the other to cold storage. All 672 recipients were followed for 1 year. The primary end point was delayed graft function (requiring dialysis in the first week after transplantation). Secondary end points were the duration of delayed graft function, delayed graft function defined by the rate of the decrease in the serum creatinine level, primary nonfunction, the serum creatinine level and clearance, acute rejection, toxicity of the calcineurin inhibitor, the length of hospital stay, and allograft and patient survival.
Machine perfusion significantly reduced the risk of delayed graft function. Delayed graft function developed in 70 patients in the machine-perfusion group versus 89 in the cold-storage group (adjusted odds ratio, 0.57; P=0.01). Machine perfusion also significantly improved the rate of the decrease in the serum creatinine level and reduced the duration of delayed graft function. Machine perfusion was associated with lower serum creatinine levels during the first 2 weeks after transplantation and a reduced risk of graft failure (hazard ratio, 0.52; P=0.03). One-year allograft survival was superior in the machine-perfusion group (94% vs. 90%, P=0.04). No significant differences were observed for the other secondary end points. No serious adverse events were directly attributable to machine perfusion.
Hypothermic machine perfusion was associated with a reduced risk of delayed graft function and improved graft survival in the first year after transplantation. (Current Controlled Trials number, ISRCTN83876362.)

Download full-text


Available from: Jean-Paul Squifflet, Jul 08, 2015
1 Follower
  • Source
    • "Prolonged cold static storage of organs for transplantation leads to tissue damage and dysfunction of the primary graft (Lima et al. 2006), as well as inferior survival of long-term grafts (Salahudeen 2004). A technological improvement of this technique, involving continuous perfusion of the graft with preservative solution using a perfusion pump, has been shown to improve cold-storage time and initial function of the graft after kidney transplant (Moers et al. 2009), but applications to other solid organs including ex-vivo perfusion of the lung have entered clinical practice, especially driven by the expansion of extended-criteria donors and by donation of organs after cardiac death (Roman et al. 2013). All forms of therapeutic cooling operate on the same unifying principle—hypothermia leads to a reduction in metabolic rate—a highly desirable response during periods of diminished supply. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Supply and demand relationships govern survival of animals in the wild and are also key determinants of clinical outcomes in critically ill patients. Most animals' survival strategies focus on the supply side of the equation by pursuing territory and resources, but hibernators are able to anticipate declining availability of nutrients by reducing their energetic needs through the seasonal use of torpor, a reversible state of suppressed metabolic demand and decreased body temperature. Similarly, in clinical medicine the majority of therapeutic interventions to care for critically ill or trauma patients remain focused on elevating physiologic supply above critical thresholds by increasing the main determinants of delivery of oxygen to the tissues (cardiac output, perfusion pressure, hemoglobin concentrations, and oxygen saturation), as well as increasing nutritional support, maintaining euthermia, and other general supportive measures. Techniques, such as induced hypothermia and preconditioning, aimed at diminishing a patient's physiologic requirements as a short-term strategy to match reduced supply and to stabilize their condition, are few and underutilized in clinical settings. Consequently, comparative approaches to understand the mechanistic adaptations that suppress metabolic demand and alter metabolic use of fuel as well as the application of concepts gleaned from studies of hibernation, to the care of critically ill and injured patients could create novel opportunities to improve outcomes in intensive care and perioperative medicine.
    Integrative and Comparative Biology 05/2014; 54(3). DOI:10.1093/icb/icu047 · 2.97 Impact Factor
  • Source
    • "The advancement of allotransplantation over the past half century has stimulated the development of techniques for whole organ preservation, especially in the face of common logistical challenges inherent in the delivery of the therapy (such as the need for transportation and coordination of operating times). In addition to preserving the function and viability of cadaveric organs accepted via standard criteria, improved organ preservation has the potential to increase the fraction of marginal organs used for transplant [60] [90]. It is generally believed that improved preservation techniques should contribute to improved maintenance of organ quality, minimize ischemia–reperfusion injury and result in more successful transplant outcomes, which has led to substantial research effort to optimize organ preservation protocols. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Improved preservation techniques have the potential to improve transplant outcomes by better maintaining donor organ quality and by making more organs available for allotransplantation. Persufflation, (PSF, gaseous oxygen perfusion) is potentially one such technique that has been studied for over a century in a variety of tissues, but has yet to gain wide acceptance for a number of reasons. A principal barrier is the perception that ex vivo PSF will cause in vivo embolization post-transplant. This review summarizes the extensive published work on heart, liver, kidney, small intestine and pancreas PSF, discusses the differences between anterograde and retrograde PSF, and between PSF and other conventional methods of organ preservation (static cold storage, hypothermic machine perfusion). Prospective implications of PSF within the broader field of organ transplantation, and in the specific application with pancreatic islet isolation and transplant are also discussed. Finally, key issues that need to be addressed before PSF becomes a more widely utilized preservation strategy are summarized and discussed.
    Cryobiology 01/2012; 64(3):125-43. DOI:10.1016/j.cryobiol.2012.01.007 · 1.64 Impact Factor
  • Source
    • "These kidneys must undergo cold preservation before transplantation. The preferred method of organ preservation in the United States is cold storage (CS), which is used in approximately 80% of transplantation cases (Maathuis et al., 2007; Moers et al., 2009). CS slows down metabolic reactions to preserve organ quality while allowing time for recipient selection and transport . "
    [Show abstract] [Hide abstract]
    ABSTRACT: The majority of kidneys used for transplantation are obtained from deceased donors. These kidneys must undergo cold preservation/storage before transplantation to preserve tissue quality and allow time for recipient selection and transport. However, cold storage (CS) can result in tissue injury, kidney discardment, or long-term renal dysfunction after transplantation. We have previously determined mitochondrial superoxide and other downstream oxidants to be important signaling molecules that contribute to CS plus rewarming (RW) injury of rat renal proximal tubular cells. Thus, this study's purpose was to determine whether adding mitoquinone (MitoQ), a mitochondria-targeted antioxidant, to University of Wisconsin (UW) preservation solution could offer protection against CS injury. CS was initiated by placing renal cells or isolated rat kidneys in UW solution alone (4 h at 4°C) or UW solution containing MitoQ or its control compound, decyltriphenylphosphonium bromide (DecylTPP) (1 μM in vitro; 100 μM ex vivo). Oxidant production, mitochondrial function, cell viability, and alterations in renal morphology were assessed after CS exposure. CS induced a 2- to 3-fold increase in mitochondrial superoxide generation and tyrosine nitration, partial inactivation of mitochondrial complexes, and a significant increase in cell death and/or renal damage. MitoQ treatment decreased oxidant production ~2-fold, completely prevented mitochondrial dysfunction, and significantly improved cell viability and/or renal morphology, whereas DecylTPP treatment did not offer any protection. These findings implicate that MitoQ could potentially be of therapeutic use for reducing organ preservation damage and kidney discardment and/or possibly improving renal function after transplantation.
    Journal of Pharmacology and Experimental Therapeutics 03/2011; 336(3):682-92. DOI:10.1124/jpet.110.176743 · 3.86 Impact Factor