Search

Deceased after circulatory death (DCD) donors offer a viable solution to the current organ shortage, particularly the Maastricht Class III (arrest subsequent to cessation of life support in the hospital). Although current results from these donors are very satisfactory, the number of included donors is too low and future expansion of inclusion criteria will likely decrease organ quality, with negative consequences on the complication rate. This donor type thus represents a priority in terms of scientific exploration, so as to study it in controlled settings and prepare for future challenges. Hence, we mimicked the DCD Class III clinical conditions a Large White pig model. Herein, we detail the different strategies attempted to attain our objectives, including technical approaches such as animal positioning and ventilator settings, as well as pharmacological intervention to modulate blood pressure and heart rate. We highlight the best combination of factors to successfully reproduce DCD Class III conditions, with perfusion pressures and functional warm ischemia (hypoperfusion) closely resembling clinical situations. Finally, we detail the functional and histological impacts of these conditions. Such a model could be of critical value to explore novel management alternative for these donors, presenting a uniquely adapted platform for such therapeutics as normothermic regional circulation and/or pharmacological intervention., Competing Interests: The authors declare that there are no conflict of interest regarding the publication of this paper., (Copyright © 2019 David Soussi et al.)

In 2012, an expert working group from the French Transplant Health Authority recommended the use of hypothermic machine perfusion (HMP) to improve kidney preservation and transplant outcomes from expanded criteria donors, deceased after brain death. This study compares HMP and cold storage (CS) effects on delayed graft function (DGF) and transplant outcomes. We identified 4,316 kidney transplants from expanded criteria donors (2011-2014) in France through the French Transplant Registry. DGF occurrence was analyzed with a logistic regression, excluding preemptive transplants. One-year graft failure was analyzed with a Cox regression. A subpopulation of 66 paired kidneys was identified: one preserved by HMP and the other by CS from the same donor. Kidneys preserved by HMP (801) vs CS (3515) were associated with more frequent recipient comorbidities and older donors and recipients. HMP had a protective effect against DGF (24% in HMP group and 38% in CS group, OR = 0.49 [0.40-0.60]). Results were similar in the paired kidneys (OR = 0.23 [0.04-0.57]). HMP use decreased risk for 1-year graft failure (HR = 0.77 [0.60-0.99]). Initial hospital stays were shorter in the HMP group (P < 0.001). Our results confirm the reduction in DGF occurrence among expanded criteria donors kidneys preserved by HMP., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Kidneys from donation after circulatory death (DCD) are highly sensitive to ischemia-reperfusion injury and thus require careful reconditioning, such as normothermic regional perfusion (NRP). However, the optimal NRP protocol remains to be characterized. NRP was modeled in a DCD porcine model (30 minutes of cardiac arrest) for 2, 4, or 6 hours compared to a control group (No-NRP); kidneys were machine-preserved and allotransplanted. NRP appeared to permit recovery from warm ischemia, possibly due to an increased expression of HIF1α-dependent survival pathway. At 2 hours, blood levels of ischemic injury biomarkers increased: creatinine, lactate/pyruvate ratio, LDH, AST, NGAL, KIM-1, CD40 ligand, and soluble-tissue-factor. All these markers then decreased with time; however, AST, NGAL, and KIM-1 increased again at 6 hours. Hemoglobin and platelets decreased at 6 hours, after which the procedure became difficult to maintain. Regarding inflammation, active tissue-factor, cleaved PAR-2 and MCP-1 increased by 4-6 hours, but not TNF-α and iNOS. Compared to No-NRP, NRP kidneys showed lower resistance during hypothermic machine perfusion (HMP), likely associated with pe-NRP eNOS activation. Kidneys transplanted after 4 and 6 hours of NRP showed better function and outcome, compared to No-NRP. In conclusion, our results confirm the mechanistic benefits of NRP and highlight 4 hours as its optimal duration, after which injury markers appear., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Donation after circulatory death (DCD) donors provides an invaluable source for kidneys for transplantation. Over the last decade, we have observed a substantial increase in the number of DCD kidneys, particularly within Europe. We provide an overview of risk factors associated with DCD kidney function and survival and formulate recommendations from the sixth international conference on organ donation in Paris, for best-practice guidelines. A systematic review of the literature was performed using Ovid Medline, Embase and Cochrane databases. Topics are discussed, including donor selection, organ procurement, organ preservation, recipient selection and transplant management., (© 2015 Steunstichting ESOT.)

Background: Deceased after cardiac death donors (DCDs) represent a valuable source of organs; however, preventing poor outcome is difficult, even with the use of machine perfusion (MP). It is of paramount importance to improve this method. We proposed to evaluate the benefits of active oxygenation during kidney graft hypothermic MP using a novel perfusion machine: Kidney Assist (KA)., Methods: We used a pig model of DCD transplantation in Large White pigs. Cold preservation was performed by conventional non-oxygenated MP (KAnoO2) or oxygenated MP (KA)., Results: In the first 2 wk post-transplant, KA grafts displayed a lower serum creatinine peak and a faster return to normal levels compared with KAnoO2 animals, translating into a smaller area under the curve. Urinary neutrophil gelatinase-associated lipocalin levels and serum aspartate amino transferase levels were lower in KA animals compared with the non-oxygenated group. These correlated with better chronic function. Longer follow-up of the animals (3 mo) permitted evaluation of chronic outcome lesions. Interstitial fibrosis was reduced in the KA group, and these kidneys also displayed significantly lower levels of vimentin staining. Further histologic investigation also showed a trend toward decreased chronic inflammation in kidneys preserved with oxygen., Conclusions: This new MP system is efficient in preserving DCD kidneys, greatly enhancing the capacity of the graft to withstand preservation stress and improving outcome. Oxygen delivery during preservation is thus valuable for highly damaged organs and offers an important therapeutic tool for transplant teams faced with decreased quality of donor organs., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose of Review: The purpose of the present review is to describe the methods using an extracorporeal membranous oxygenation (ECMO) circuit in donors after cardiac death and to evaluate their impact on the outcome of renal transplantation., Recent Findings: ECMO can be used either in hypothermic conditions for total body cooling or in normothermic conditions and limited to the abdomen in a first phase, before subsequent in-situ cooling. In both cases, oxygen is added to the perfusion, as compared with the usual and simple cold in-situ perfusion. There is a strong experimental rationale to use ECMO in normothermic conditions. The clinical studies in renal transplantation are still few, retrospective with small cohorts (level 3 or 4, according to the Oxford Centre for Evidence-Based Medicine). However, they all reach consistent conclusions with better kidney transplant outcome, both in uncontrolled (type I and II) and controlled (type III) donors, according to the Maastricht classification., Summary: The use of ECMO in donors after cardio-circulatory death should be encouraged and further developed. Experimental work is in progress to better define the optimal conditions of the technique, which will help to limit or even repair the injuries, induced by warm ischaemia.

Organ donation after cardiac death has been used for kidney and liver procurement in France since 2006. Until recently, most teams relied on in situ cold perfusion to prepare the donor before organ retrieval. Our team has used since 2007 normothermic abdominal recirculation. While this technique is presumed to be more difficult to implement, it also ensures a lower rate of primary nonfunction when compared to in situ cold perfusion. We present the efficiency results of our organ donation after cardiac death program. After 3 years, we have been able to establish a program in which we use normothermic abdominal recirculation in 97% of donors after cardiac death. The yearly efficiency of this program is comparable to the national efficiency of organ procurement from conventional deceased donors in France., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The organ shortage has led to extend the procurement to kidneys from 'marginal' donors. As a result, an increasing number of kidneys are discarded, but an extended analysis of the validity of the clinical decision to accept or decline a marginal graft remains to be determined. We have retrospectively analyzed the outcome of 170 kidney transplantations, performed in eight renal transplantation centers between 1992 and 1998. Study group included transplantation from donors accepted after refusal for poor donor or graft quality by at least two centers. Control group included 170 paired recipients from kidneys unanimously accepted by all centers. Main causes of kidney refusal included impaired donor hemodynamics (28%), abnormal pre-harvesting serum creatinine (22%), advanced age in donors (15%), and donor atheroma (14%). The 5-year patient survival (88.2% in the study group and 88.9% in controls) and graft survival (70.4% in the study group and 76.7% in controls, P=0.129) were not significantly different. Delayed graft function occurred significantly more often in the study group patients than in controls patients (63 vs 32%, P<0.0001). Primary non-functioning kidneys were significantly more frequently observed in study patients than in controls (7.7 vs 1.8%, P=0.01). Mean creatinine clearance was significantly lower in the study group patients compared with controls during the post-transplant course. Our results suggest that these initially discarded kidneys provide satisfactory survival rates despite their impaired early functional recovery and poorer long-term renal function, and therefore might be considered acceptable for transplantation in the context of organ shortage.

Objective: To evaluate the quality of the postoperative course after conventional organ donation nephrectomy., Patients and Methods: Over the last 29 months, 29 organ donation nephrectomies were performed in our hospital. Thirteen donors were non-residents. This series consisted of twenty organ donations between siblings, two organ donations from children to parents and seven organ donations from parents to children. The mean age of the donors was 42 years (range: 21 to 53). Ten pairs were HLA identical, 18 were semi-identical and one pair had only one A identity in common. The mean plasma creatinine on admission was 81 +/- 23 mumol/l., Results: Twenty three left kidneys and 3 right kidneys were harvested, with the last two right kidneys removed via a right anterior subcostal incision. Among the 23 left lumbotomies, the 11th rib was preserved in 21 cases in order to decrease postoperative pain. The mean operating time for patients operated by lumbotomy was 90 +/- 11 minutes. The mean postoperative stay (MPS) was 4.56 days (range: 3 to 8 days). The mean morphine consumption during hospitalisation was 40 mg per patient (range: 0 to 105 mg). Only one complication was observed: pneumothorax requiring postoperative drainage for 48 hours with no subsequent sequelae. No donor was transfused intraoperatively or postoperatively and no wound sequelae were observed. The mean plasma creatinine on discharge was 113 +/- 23 mumol/l., Conclusion: These results in terms of analgesic consumption, complications, and mean postoperative stay appear to compare favourably with those obtained by other teams, particularly when organ harvesting is performed laparoscopically (MPS: 4.5 days vs 3 days).

Although the mouse spleen dendritic cell (DC) is perhaps the most intensively studied DC type, little has been published concerning its human equivalent. In this report, rare event flow cytometry and in situ immunofluorescence were used to study the surface phenotype and distribution of HLA-DR(+) CD3(-)14(-)16(-)19(-) human spleen DC. Spleens from organ donors with different clinical histories were used. Most (81% +/- 9%; n = 14) spleen DCs expressed high levels of the integrin CD11c. CD11c(+) DCs were distributed in 3 distinct regions-the peri-arteriolar T-cell zones, the B-cell zones, and the marginal zone, where they formed a ring of cells surrounding the white pulp, just inside a ring of CD14(+) red pulp macrophages, apparently more regularly organized than the previously described marginating DC population in the mouse spleen. The T-cell zones contained CD86(+) DCs, among which a subpopulation expressed CD83. These mature/activated CD86(+) DCs represented a minority (12% +/- 8%) of total spleen DCs in most organ donors: most spleen DCs are immature. In 3 of 18 (17%) donors, however, most (54%-81%) of spleen DCs were CD86(+), suggesting that in vivo DC activation had occurred. In one donor, a radical shift in DC distribution from the marginal zone to the T-cell zones was also observed. This activation of spleen DCs in vivo was reminiscent of the effects of experimental microbial product injection in mice, and it seemed to correlate with bacterial infection or multiple trauma. (Blood. 2001;97:3470-3477)

Background: Diabetes insipidus is common among brain-dead donors and may lead to decreased graft function. The use of desmopressin to limit the consequences of diabetes insipidus is controversial. We assessed the effects of desmopressin administered to brain-dead donors on early and long-term graft function in kidney recipients., Methods: In a randomised controlled study, 97 brain-dead donors received desmopressin as 1 microg bolus every 2 h when diuresis was more than 300 mL/h (desmopressin group n=49) or no desmopressin (control group n=48). In 175 kidney recipients (controls n=89, desmopressin group n=86) we measured serum concentrations of creatinine and haemodialysis requirements to assess early renal function in the first 15 days after transplantation. We assessed long-term results of transplantation (median time 45 months) for a homogeneous subgroup of 95 recipients (48 in the desmopressin group)., Findings: We found no significant differences between the two groups of brain-dead donors, except for final diuresis, which was lower in the desmopressin group than among controls. Haemodialysis requirement in controls and the desmopressin group (20 vs 23%, p=0.63) and serum creatinine concentrations (decrease from 903 micromol/L to 206 micromol/L vs 814 micromol/L to 193 micromol/L, p=0.14) did not differ significantly in the first 15 days after transplantation. Long-term graft survival was similar in the two groups (88 vs 87%)., Interpretation: Desmopressin can be given to brain-dead donors to limit the harmful effects of diabetes insipidus without any substantial effects to graft function in recipients.