48 research outputs found

    Non-heart beating organ donation: overview and future perspectives.

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    New indications for organ transplantation combined with a stagnating number of available donor grafts have severely lengthened the waiting list for almost all types of transplantations. This has led to a renewed interest in non-heart beating (NHB) donation, as a possible solution to bridge the gap between supply and demand. In this review, we present an overview of current NHB donation practice, outcome, existing problems and future perspectives. We focus on possible improvements in donor management, recipient care and new methods of organ preservation that may be better suited for these marginal organs. Successful institution of NHB protocols depends on adapting current transplantation practice at all levels, which is one of the greatest challenges for researchers and professionals in this interesting re-emerging field

    Perspectives in organ preservation.

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    Maintaining organ viability after donation until transplantation is critically important for optimal graft function and survival. To date, static cold storage is the most widely used form of preservation in every day clinical practice. Although simple and effective, it is questionable whether this method is able to prevent deterioration of organ quality in the present era with increasing numbers of organs retrieved from older, more marginal, and even non-heart-beating donors. This review describes principles involved in effective preservation and focuses on some basic components and methods of abdominal organ preservation in clinical and experimental transplantation. Concepts and developments to reduce ischemia related injury are discussed, including hypothermic machine perfusion. Despite the fact that hypothermic machine perfusion might be superior to static cold storage preservation, organs are still exposed to hypothermia induced damage. Therefore, recently some groups have pointed at the beneficial effects of normothermic machine perfusion as a new perspective in organ preservation and transplantation

    The influence of deceased donor age and old-for-old allocation on kidney transplant outcome.

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    BACKGROUND: Transplantation of older deceased donor kidneys is gaining wide acceptance in most countries. Many previous studies have concluded that advanced donor age negatively impacts posttransplant outcome, but detailed data on the extent to which a few years increase in donor age will influence early graft function and graft survival are scarce. METHODS: We used the Organ Procurement and Transplantation Network database (cohort 1994-2006, n=99,860 recipients) to evaluate the effect of deceased donor age on posttransplant results and to obtain regression models which are relevant to guide clinical organ allocation policies. In addition, we simulated the effect that old-for-old allocation would have on transplant outcome. RESULTS: In the context of other risk factors, donor age increased the risk of delayed graft function and graft failure with odds and hazard ratios of 1.02 and 1.01, respectively. Absolute delayed graft function risk increased by 0.35% to 0.37%, and graft survival decreased with each year increase in donor age. Kidney discard rates in the United States increased with donor age, up to 66.9% for 65 years and older donors. In our simulation, we found that old-for-old kidney allocation would have no large impact on overall renal transplant outcome. CONCLUSIONS: This study shows that donor age strongly influences posttransplant outcome, not only in the upper extremes but also for the whole range of donor ages more than or equal to 11 years. Implementation of old-for-old kidney allocation is likely to be safe. Such a policy could reduce waiting time for aged candidates, but it will not necessarily improve overall kidney transplant outcome

    [A successful transplant begins with organ preservation]

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    Organ preservation is a critical link in the chain of donation and transplantation and has a significant effect on post-transplant graft function and graft survival. Clinically, the most widely used form of preservation is static cold storage, which is based on the reduction of cellular metabolism by hypothermia. Although static cold storage is simple and effective, it is questionable whether it still meets present day requirements. Due to the persistent shortage of donors, increasing numbers of organs are being accepted from older and non-heart-beating donors. Organs from such donors may benefit from a more dynamic method of preservation: hypothermic machine perfusion

    How important is the duration of the brain death period for the outcome in kidney transplantation?

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    In kidney transplantation, graft survival using grafts from donation after brain death (DBD) donors is inferior to results after living donation. However, little is known about the effect of the duration of brain death (BDdur) on outcome after transplantation. This is a retrospective Organ Procurement and Transplant Network analysis using kidney donor and recipient data from 1994 to 2006. BDdur was calculated as the period between brain death declaration and aortic cross clamp. Effects of BDdur on delayed graft function (DGF), acute rejection and graft failure were calculated using binary logistic regression and Cox regression models. Median BDdur was 23.8 h. Longer BDdur decreased the risk for DGF and 1- and 3-year graft failure slightly, but not for acute rejection. In multivariate analysis, donor age and acute rejection were confounders. However, in a multivariate subgroup analysis of donors aged ≤ 55 years BDdur independently predicted DGF; each hour of BDdur decreasing the risk of DGF with 0.4% (P = 0.008). Longer BDdur is not detrimental and in fact slightly beneficial in DBD donors ≤ 55 years of age, reducing the chance of DGF in the recipient. This finding may have an impact on organ retrieval procedures, as no rush but rather an improved donor management prior to retrieval will benefit donor kidney viability

    Activation of hemostasis in brain dead organ donors: an observational study.

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    BACKGROUND: Brain death is associated with a systemic inflammatory response resulting in diminished organ function in individuals transplanted with organs from brain dead donors. As inflammation is accompanied by activation of coagulation, we hypothesized that activation of hemostasis occurs in brain dead organ donors. OBJECTIVES: To assess the hemostatic status in brain dead organ donors. PATIENTS AND METHODS: In this study, we systematically assessed the hemostatic system in samples taken from 30 brain dead donors. As controls, blood samples from 30 living kidney donors were included. RESULTS AND CONCLUSIONS: Compared with the living donors, brain dead donors showed significant platelet activation (assessed by glycocalicin plasma levels), and a profound dysbalance in the von Willebrand factor/ADAMTS13 axis, which is key in platelet attachment to damaged vasculature. Furthermore, compared with the living donors, brain dead donors showed a significantly increased activation of secondary hemostasis with formation of fibrin (assessed by plasma levels of prothrombin fragment 1 + 2, fibrinopeptide A and D-dimer). Finally, brain dead donors showed profound hypofibrinolysis as assessed by a global clot lysis assay, which was attributed to substantially elevated plasma levels of plasminogen activator inhibitor type 1. Collectively, our results show activation of hemostasis and dysregulated fibrinolysis in brain dead organ donors. This prothrombotic state may contribute to formation of microthrombi in transplantable organs, which potentially contributes to deterioration of organ function

    Deterioration of endothelial and smooth muscle cell function in DCD kidneys after static cold storage in IGL-1 or UW.

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    BACKGROUND: Kidneys obtained from donors after cardiac death are damaged by the combination of warm and cold ischemia. Although the parenchymal damage of these kidneys is well studied, little is known about the functional effects of warm and cold ischemia on the renal vascular bed. We compared kidney preservation using the new extracellular-type cold storage solution from Institut Georges Lopez (IGL-1) with the University of Wisconsin solution (UW) and focused on vasomotor functions. METHODS: The influence of warm and cold ischemia on vasomotor functions was studied in an isolated perfused kidney model. Six groups of donation after cardiac death donor kidneys were studied with warm ischemia of 0, 15, and 30 min followed by 0 or 24 h cold storage preservation in IGL-1 or UW at 4 degrees C. Endothelial dependent vasodilation was studied using acetylcholine, smooth muscle cell (SMC) constriction was assessed using phenylephrine, and finally endothelial independent relaxation was tested using papaverine-sulfate. RESULTS: SMCs were significantly affected by cold ischemia showing a 50% reduction of phenylephrine mediated constriction after preservation. Additional warm ischemia did not affect SMCs. After UW preservation endothelial dependent vasodilation was only significantly reduced when the combination of warm and cold ischemia was present. IGL-1 preserved kidneys showed a reduction in endothelial dependent vasodilation after isolated warm ischemia. Both preservation solutions rendered equal results after 24 h preservation. CONCLUSION: Vasomotor functions are negatively influenced by the combination of warm and cold ischemia. Both IGL-1 and UW performed equally in preserving vasomotor functions. The interesting finding of the rapid decline of SMC function might point at the first step toward intimal hyperplasia as seen in late transplant dysfunction

    Kidney grafts from brain dead donors: Inferior quality or opportunity for improvement?

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    Major improvements in immunosuppressive treatment, surgical techniques, and treatment of post-transplant complications have contributed considerably to improved outcome in renal transplantation over the past decades. Yet, these accomplishments have not led to similar improvements in transplant outcome when the results of living and deceased donors are compared. The enormous demand for donor kidneys has allowed for the increase in acceptance of suboptimal donors. The use of brain dead patients as organ donors has had a tremendous positive influence on the number of renal transplants. Unfortunately, the physiologically abnormal state of brain death has a negative effect on transplant outcome. The fact that transplanted kidneys derived from brain dead donors have a decreased viability indicates that potential grafts are already damaged before retrieval and preservation. In this review, we present an overview of the current knowledge of (patho)-physiological effects of brain death and its relevance for renal transplant outcome. In addition, several options for therapeutic intervention during brain death in the donor with the goal to improve organ viability and transplant outcome are discussed
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