Editor's Choice - European Society for Vascular Surgery (ESVS) 2019 Clinical Practice Guidelines on the Management of Abdominal Aorto-iliac Artery Aneurysms.

BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.)

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Machine Perfusion or Cold Storage in Deceased-Donor Kidney Transplantation

BackgroundMore than 80% of donor lungs are potentially injured and therefore not considered suitable for transplantation. With the use of normothermic ex vivo lung perfusion (EVLP), the retrieved donor lung can be perfused in an ex vivo circuit, providing an opportunity to reassess its function before transplantation. In this study, we examined the feasibility of transplanting high-risk donor lungs that have undergone EVLP. MethodsIn this prospective, nonrandomized clinical trial, we subjected lungs considered to be high risk for transplantation to 4 hours of EVLP. High-risk donor lungs were defined by specific criteria, including pulmonary edema and a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PO2:FIO2) less than 300 mm Hg. Lungs with acceptable function were subsequently transplanted. Lungs that were transplanted without EVLP during the same period were used as controls. The primary end point was primary graft dysfunction 72 hours after transplantation. Secondar...

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Normothermic Ex Vivo Lung Perfusion in Clinical Lung Transplantation

The definitive treatment for end-stage organ failure is orthotopic transplantation. However, the demand for transplantation far exceeds the number of available donor organs. A promising tissue-engineering/regenerative-medicine approach for functional organ replacement has emerged in recent years. Decellularization of donor organs such as heart, liver, and lung can provide an acellular, naturally occurring three-dimensional biologic scaffold material that can then be seeded with selected cell populations. Preliminary studies in animal models have provided encouraging results for the proof of concept. However, significant challenges for three-dimensional organ engineering approach remain. This manuscript describes the fundamental concepts of whole-organ engineering, including characterization of the extracellular matrix as a scaffold, methods for decellularization of vascular organs, potential cells to reseed such a scaffold, techniques for the recellularization process and important aspects regarding biore...

https://www.annualreviews.org/doi/pdf/10.1146/annurev-bioeng-071910-124743

Whole-Organ Tissue Engineering: Decellularization and Recellularization of Three-Dimensional Matrix Scaffolds

The definitive treatment for end-stage organ failure is orthotopic transplantation. However, the demand for transplantation far exceeds the number of available donor organs. A promising tissue-engineering/regenerativemedicine approach for functional organ replacement has emerged in recent years. Decellularization of donor organs such as heart, liver, and lung can provide an acellular, naturally occurring three-dimensional biologic scaffold material that can then be seeded with selected cell populations. Preliminary studies in animal models have provided encouraging results for the proof of concept. However, significant challenges for three-dimensional organ engineering approach remain. This manuscript describes the fundamental concepts of whole-organ engineering, including characterization of the extracellular matrix as a scaffold, methods for decellularization of vascular organs, potential cells to reseed such a scaffold, techniques for the recellularization process and important aspects regarding bioreactor design to support this approach. Critical challenges and future directions are also discussed.

Whole-Organ Tissue Engineering: Decellularization and Recellularization of Three-Dimensional

Categories of non-heart-beating donors.

The asystolic, or non-heartbeating, donor.

Background. The ability to effectively utilize kidneys damaged by severe (2 hr) warm ischemia (WI) could provide increased numbers of kidneys for transplantation. The present study was designed to examine the effect of restoring renal metabolism after severe WI insult during ex vivo warm perfusion using an acellular technology. After warm perfusion for 18 hr, kidneys were reimplanted and evaluated for graft function. Methods. Using a canine autotransplant model, kidneys were exposed to 120 min of WI. They were then either reimplanted immediately, hypothermically machine perfused (4°C) for 18 hr with Belzer’s solution, or transitioned to 18 hr of warm perfusion (32°C) with an acellular perfusate before implantation. Results. Warm perfused kidneys with 120 min of WI provided life-sustaining function after transplantation, whereas the control kidneys immediately reimplanted or with hypothermic machine perfusion did not. The mean peak serum creatinine in the warm perfused kidneys was 3.7 mg/dl, with the mean peak occurring on day 2 and normalizing on day 9 posttransplant. Conclusions. These results indicate that 18 hr of ex vivo warm perfusion of kidneys is feasible. Furthermore, recovery of renal function during warm perfusion is demonstrated, resulting in immediate function after transplantation. The use of ex vivo warm perfusion to recover function in severe ischemically damaged kidneys could provide the basis for increasing the number of transplantable kidneys. For the past decades the organ donor pool has consisted largely of the ICU-based, heart-beating, cadaver donor, which represents a limited pool of potential donors. Despite concerted efforts, the number of organs available for transplantation has remained stagnant over the past 10 years (1, 2). Recent attempts to provide more kidneys have focused on using non-heart-beating (NHB) donors with limited warm ischemia (30 min). Unfortunately the posttransplant outcomes with these kidneys are characterized by a high incidence of both delayed graft function and primary nonfunction, thereby hampering effective use of the NHB donor kidney. The major obstacle preventing any substantial expansion of the donor pool is warm ischemia (WI) combined with cold preservation (3). Although it has been proposed that the kidney can tolerate as much as 2 hr of WI before the damage becomes irreversible, the added cold ischemia used to preserve the kidney during the period of tissue typing, matching, and transportation has made WI of greater than 30 min an insurmountable obstacle in transplantation today. Although the WI insult is unavoidable in using kidneys from the NHB donor, an alternative to traditional hypothermic inhibition of metabolism may be feasible. Our hypothesis was that an acellular warm perfusion after WI could reestablish metabolism, restore vascular integrity, and re-institute cell volume regulation ex vivo sufficiently to render severely damaged kidneys capable of providing life-sustaining function when reimplanted. To test this hypothesis, a canine autotransplant model consisting of an initial WI insult of 120 min was employed. Exsanguinous metabolic support (EMS) technology was used for ex vivo warm perfusion (32°C) for 18 hr.

Overcoming severe renal ischemia: the role of ex vivo warm perfusion.

Given the shortage of donor kidneys for transplantation, we have focused on the use of non heart-beating (NHB) donor kidneys since 1982. The major drawback for the use of NHB donor kidneys is the inherent possibility of severe ischaemic damage leading to primary non function. Thus viability assessment of ischaemically damaged kidneys is crucial, and, therefore, a machine perfusion programme was reinstituted in 1993. Machine perfusion (MP) enables viability assessment through analysis of perfusion characteristics and measurement of enzyme release into the perfusate. Of the last 100 consecutive MP NHB donor kidneys, 71 kidneys were transplanted and 29 kidneys were discarded. Nine kidneys started functioning immediately, 51 kidneys showed delayed function and 11 kidneys never functioned. When analysing in retrospect different parameters for viability assessment, only alpha-GST, an enzyme specific for damage of proximal tubular cells within the kidney, could discriminate between functioning and non-functioning kidneys. With this promising viability assessment, the large NHB donor potential and the good transplant results, we recommend the use of these donors.

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The non heart-beating donor

One of the ways to fight the growing organ shortage in transplantation is by procuring organs from non-heart-beating (NHB) donors. In order to determine the NHB kidney donor pool and evaluate its significance for renal transplantation, the potential is estimated in this study by retrospective death chart review. All 200 in-hospital deaths aged 3-65 yr reported at the University Hospital Maastricht in 1994, including 25 deaths at the Emergency Department (ED), were analyzed. After exclusion of deaths by computerized ICD-9-CM codes, 109 charts were abstracted and reviewed by experts. As a result a potential of eight brain dead, heart-beating (HB) donors and 56 NHB donors were identified. Medical suitability and logistic availability were scored in an attempt to quantify the likelihood of the donation to proceed towards successful organ procurement. These scores resulted in a range of potential NHB donors from 4.5 to 9.2 per 100 in-hospital deaths. Including rates of refusal to consent, as well as rates of technical failures, 24.0-49.6 kidneys were calculated to be realistically available annually, 2-4.5 times the projected number of kidneys from HB donors. With this increase of available grafts, at least growth of the renal waiting list would be prevented. This estimate shows that the potential of NHB kidney donors is large, and its impact on organ shortage would be considerable. Since 68% of potential NHB kidney donors, and also 70% of the medically most suitable donors, were found in ED, ICU, and CCU, focusing on these hospital units for implementation of routine procurement of kidneys from NHB donors is probably most effective. We therefore plead for the introduction of NHB kidney procurement protocols in EDs, ICUs, and CCUs.

Gauke Kootstra

Papers

Categories of non-heart-beating donors.

The asystolic, or non-heartbeating, donor.

Overcoming severe renal ischemia: the role of ex vivo warm perfusion.

The non heart-beating donor

The potential pool of non-heart-beating kidney donors.