DCD Kidneys Research Articles

Kidney transplantation following uncontrolled donation after circulatory death.

The identification and utilization of kidneys from uncontrolled donation after circulatory death (uDCD) donors for transplantation may increase transplantation rates markedly. This article summarizes the latest international results from successful uDCD kidney transplant programmes and considers how such programmes may impact on the transplant waiting list. The results of more than 1000 uDCD donor kidney transplants have been reported since 2007 from France and Spain. Estimates from France, Spain and Sweden suggest that effective utilization of the potential uDCD donor pool might increase donation rates by 25%. The main concern relating to uDCD kidney transplantation is the high incidence of primary nonfunction with the incidence of primary nonfunction reported as 7-8% even with careful donor selection and the use of normothermic regional perfusion at the time of organ recovery. Notwithstanding, reported 1- year graft survival figures are equivalent to those from expanded criteria donors (ECD) and 10-year graft survival of between 72 and 82% was reported in the two single-centre series with longest reported follow-up period. Uncontrolled DCD kidney transplantation has been successfully implemented in several regions in France and Spain. Wider implementation of uDCD programmes would increase substantially the number of kidneys for transplantation, while maintaining acceptable transplant outcomes.

Mesenchymal Stromal Cell Treatment of Kidneys During Normothermic Machine Perfusion is Safe and Feasible with Effective Traceability after Transplantation

Lohmann 1/M. Pool 2, K. Rozenberg 3, M. Eijken 4, U. Møldrup 5, B.K. Møller 6, J.M. Sierra Parraga 7, M. Hoogduijn 7, L. Lo Faro 3, C. Moers 2, J. Hunter 3, A.K. Keller 1, H. Leuvenink 2, C.C. Baan 7, R.J. Ploeg 3, B. Jespersen 1
 
 Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
 Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands
 Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom
 Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark
 Department of Urology, Aarhus University Hospital, Aarhus, Denmark
 Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark
 Department of Internal Medicine, Nephrology and Transplantation, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
 
 Introduction
 Marginal kidneys are increasingly being accepted to decrease waiting time for a transplant. Normothermic machine perfusion (NMP) is a technique that allows delivery of therapies that may help condition or repair the organ prior to transplantation. Mesenchymal stromal cells (MSC) may be able to ameliorate ischaemia reperfusion injury as they possess potent anti-inflammatory and regenerative properties. We investigated the safety and effect of MSCs administered during ex vivo NMP prior to transplantation in a pig auto-transplant model of donation after circulatory death.
 Methods 
 Porcine kidneys subjected to 75 min warm ischaemia were retrieved and preserved for 14h by oxygenated HMP (oxHMP) and 4h NMP and then auto-transplantation. Kidneys were randomised to three different intervention strategies (n=7 per group): following 1h NMP, either a vehicle (NMP), 10 million pig MSC (NMP+pMSC) or 10 million human MSC (NMP+hMSC) were intra-arterially infused. The NMP groups were all compared to a control group, where kidneys were only preserved with oxHMP. The pig was re-anaesthetised, the contralateral kidney was removed and the treated kidney was auto-transplanted and the animals were recovered for 14 days.
 Results
 Renal blood flow during NMP was no different between the groups (p=0.0685). Post-transplant plasma creatinine increased in all groups but there were no significant differences between the groups (p=0.517). Plasma kidney injury biomarker NGAL was significantly higher in the NMP+pMSC group compared to the NMP (p=0.003) and NMP+hMSC (p=0.017) groups at day 14. On day 14, mGFR significantly improved in the NMP group compared to the control (55 ± 3 vs 42 ± 12 ml/min, p=0.025). No differences in GFR were observed on day 14 in the other groups (NMP+pMSC, p=0.090 and NMP+hMSC, p=0.387). MSC were detectable in biopsies of MSC treated kidney after NMP and post-transplantation.
 Conclusion 
 NMP alone improved renal graft function compared to oxHMP of DCD kidneys post-transplant. The method of MSC administration during NMP proved to be safe, however in this model MSC treatment did not improve renal function. Nevertheless viable MSC remained detectable in the transplanted kidney at postoperative day 14 which may have an effect on longer term outcomes.

Comparison of Graft Outcome Between Donation After Circulatory Death and Living-Donor Kidney Transplantation

BackgroundDonation after cardiac death (DCD) and living-donor (LD) kidney transplantation are the main kidney transplantation types in China. But the outcome of DCD kidney transplantation compared with LD kidney transplantation remains unclear. MethodsIn this study, 325 DCD and 409 LD kidney transplantations were included. We retrospectively compared 3-year graft survival, death-censored graft survival, recipient survival, and graft function. All kidneys of the DCD group were procured from voluntary donation after the citizens' death by the Organ Procurement Organization (OPO) in the presence of the Red Cross, and the transplantation application was approved by the Organ Transplant Ethics Committee. ResultsThe graft function at year 3 in the DCD group was superior to that of the LD group (eGFR: 71.14±22.28 vs 64.29±16.76 mL/min/1.73 m2; P < .001). After matching donor age, there was no significant difference between the paired DCD and LD group (eGFR: 62.22±18.50 vs 66.99±17.81 mL/min/1.73 m2; P = .068). The 3-year graft survival (94.7% vs 97.4%; P = .041) and recipient survival (97.2% vs 99.5%; P = .011) were a little worse in the total DCD group. However, once the DCD kidney transplantation recipients survived more than 2 months, graft and recipient survival rates were similar between the DCD and LD groups (97.7% vs 97.4%, P = .866 and 99.5% vs 99.0%, P = .466). These results were confirmed in an age-paired groups study. Severe infection was the main cause of graft loss and recipient death in the early stage of DCD transplantation. ConclusionsMedium- and long-term graft function of DCD kidney transplantation were comparable to LD kidney transplantation. Our results supported the continued use of DCD kidneys.

Missed opportunities for DCD kidney donors: Evaluation of warm ischemic time and associated functional warm ischemic time.

Many transplant centers utilize a hard cutoff of 2hours of warm ischemic time (WIT), defined as the time from withdrawal of life-sustaining measures to cold organ flush, to exclude donation after circulatory determination of death (DCD) kidney donation. As a result, almost a quarter of withdrawals to retrieve DCD organs fail to produce kidney transplants in Ontario. In order to assess our ability to increase organ yield, we wanted to characterize WIT and functional WIT (fWIT, time from systolic blood pressure <50mmHg to cold organ flush), as well as determine the time at which potential donors eventually die in those that did not become organ donors. A retrospective review of all DCD kidney donors in Ontario was performed utilizing the Trillium Gift of Life Database from April 2013 to February 2018. Of 350 DCD kidney donors analyzed, 46.9% had <0.5hours, 51.7% between 0.5 and 2hours, and 1.4% >2hours of WIT. In each of these categories (WIT <0.5hours, 0.5-2hours and >2hours), the percentage of patients with fWIT <30minutes was 100%, 94.4%, and 100%, respectively (P=NS). There were 106 potential donors who did not end up donating due to WIT >2hours. Of these, 20.8% died between 2 and 4hours, 10.4% between 4 and 6hours, and 68.8% beyond 6hours. The percentage of donors with fWIT >30minutes did not increase with increasing WIT in DCD donors that went on to donate organs. These data support assessment of waiting up to 4hours for DCD kidney donation as long as fWIT remains low.

Donation after cardiac death kidneys are suitable for pediatric recipients.

Despite the high number of children listed for kidney transplantation and shortage of deceased organ donors, there is reluctance to utilize DCD kidneys in pediatric recipients. We examined outcomes in pediatric kidney transplant patients who received a DCD kidney allograft. UNOS database was queried to examine outcomes in all pediatric kidney transplant recipients from 1994 to 2017. Pediatric status was defined as <18years at the time of transplantation. Recipients were divided by DBD or DCD allograft status. Donor and recipient demographic data were examined. Patient and allograft survival was calculated, and Kaplan-Meier survival curves were generated. A P-value of <0.05 was considered to be significant. A total of 286 pediatric kidney transplant recipients received a DCD allograft. The donors in the DCD group were significantly younger than those in the DBD group (21.7 vs 23.3years), with a higher KDPI (26.5% vs 22.9%). In the DCD group, the average age at transplant was younger (11.6 vs 12.9years), with no difference in cold ischemia time or length of stay between the two groups. Rates of delayed graft function were higher in the DCD group, but despite this, there were no significant differences in allograft or patient survival between the groups. There is no difference in allograft survival in pediatric kidney transplant recipients who receive a DCD kidney allograft. DCD kidney allografts are suitable for transplantation in pediatric patients and can greatly expand the donor pool.

Machine perfusion preservation versus static cold storage for deceased donor kidney transplantation.

Kidney transplantation is the optimal treatment for end-stage kidney disease. Retrieval, transport and transplant of kidney grafts causes ischaemia reperfusion injury. The current accepted standard is static cold storage (SCS) whereby the kidney is stored on ice after removal from the donor and then removed from the ice box at the time of implantation. However, technology is now available to perfuse or "pump" the kidney during the transport phase or at the recipient centre. This can be done at a variety of temperatures and using different perfusates. The effectiveness of treatment is manifest clinically as delayed graft function (DGF), whereby the kidney fails to produce urine immediately after transplant. To compare hypothermic machine perfusion (HMP) and (sub)normothermic machine perfusion (NMP) with standard SCS. We searched the Cochrane Kidney and Transplant Register of Studies to 18 October 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. All randomised controlled trials (RCTs) and quasi-RCTs comparing HMP/NMP versus SCS for deceased donor kidney transplantation were eligible for inclusion. All donor types were included (donor after circulatory (DCD) and brainstem death (DBD), standard and extended/expanded criteria donors). Both paired and unpaired studies were eligible for inclusion. The results of the literature search were screened and a standard data extraction form was used to collect data. Both of these steps were performed by two independent authors. Dichotomous outcome results were expressed as risk ratio (RR) with 95% confidence intervals (CI). Continuous scales of measurement were expressed as a mean difference (MD). Random effects models were used for data analysis. The primary outcome was incidence of DGF. Secondary outcomes included: one-year graft survival, incidence of primary non-function (PNF), DGF duration, long term graft survival, economic implications, graft function, patient survival and incidence of acute rejection. No studies reported on NMP, however one ongoing study was identified.Sixteen studies (2266 participants) comparing HMP with SCS were included; 15 studies could be meta-analysed. Fourteen studies reported on requirement for dialysis in the first week post-transplant (DGF incidence); there is high-certainty evidence that HMP reduces the risk of DGF when compared to SCS (RR 0.77; 95% CI 0.67 to 0.90; P = 0.0006). HMP reduces the risk of DGF in kidneys from DCD donors (7 studies, 772 participants: RR 0.75; 95% CI 0.64 to 0.87; P = 0.0002; high certainty evidence), as well as kidneys from DBD donors (4 studies, 971 participants: RR 0.78, 95% CI 0.65 to 0.93; P = 0.006; high certainty evidence). The number of perfusions required to prevent one episode of DGF (number needed to treat, NNT) was 7.26 and 13.60 in DCD and DBD kidneys respectively. Studies performed in the last decade all used the LifePort machine and confirmed that HMP reduces the incidence of DGF in the modern era (5 studies, 1355 participants: RR 0.77, 95% CI 0.66 to 0.91; P = 0.002; high certainty evidence). Reports of economic analysis suggest that HMP can lead to cost savings in both the North American and European settings.Two studies reported HMP also improves graft survival however we were not able to meta-analyse these results. A reduction in incidence of PNF could not be demonstrated. The effect of HMP on our other outcomes (incidence of acute rejection, patient survival, hospital stay, long-term graft function, duration of DGF) remains uncertain. HMP is superior to SCS in deceased donor kidney transplantation. This is true for both DBD and DCD kidneys, and remains true in the modern era (studies performed in the last decade). As kidneys from DCD donors have a higher overall DGF rate, fewer perfusions are needed to prevent one episode of DGF (7.26 versus 13.60 in DBD kidneys).Further studies looking solely at the impact of HMP on DGF incidence are not required. Follow-up reports detailing long-term graft survival from participants of the studies already included in this review would be an efficient way to generate further long-term graft survival data.Economic analysis, based on the results of this review, would help cement HMP as the standard preservation method in deceased donor kidney transplantation.RCTs investigating (sub)NMP are required.

Predictive Score Model for Delayed Graft Function Based on Hypothermic Machine Perfusion Variables in Kidney Transplantation

Background:Hypothermic machine perfusion (HMP) is being used more often in cardiac death kidney transplantation; however, the significance of assessing organ quality and predicting delayed graft function (DGF) by HMP parameters is still controversial. Therefore, we used a readily available HMP variable to design a scoring model that can identify the highest risk of DGF and provide the guidance and advice for organ allocation and DCD kidney assessment.Methods:From September 1, 2012 to August 31, 2016, 366 qualified kidneys were randomly assigned to the development and validation cohorts in a 2:1 distribution. The HMP variables of the development cohort served as candidate univariate predictors for DGF. The independent predictors of DGF were identified by multivariate logistic regression analysis with a P < 0.05. According to the odds ratios (ORs) value, each HMP variable was assigned a weighted integer, and the sum of the integers indicated the total risk score for each kidney. The validation cohort was used to verify the accuracy and reliability of the scoring model.Results:HMP duration (OR = 1.165, 95% confidence interval [CI ]: 1.008–1.360, P = 0.043), resistance (OR = 2.190, 95% CI: 1.032–10.20, P < 0.001), and flow rate (OR = 0.931, 95% CI: 0.894–0.967, P = 0.011) were the independent predictors of identified DGF. The HMP predictive score ranged from 0 to 14, and there was a clear increase in the incidence of DGF, from the low predictive score group to the very high predictive score group. We formed four increasingly serious risk categories (scores 0–3, 4–7, 8–11, and 12–14) according to the frequency associated with the different risk scores of DGF. The HMP predictive score indicates good discriminative power with a c-statistic of 0.706 in the validation cohort, and it had significantly better prediction value for DGF compared to both terminal flow (P = 0.012) and resistance (P = 0.006).Conclusion:The HMP predictive score is a good noninvasive tool for assessing the quality of DCD kidneys, and it is potentially useful for physicians in making optimal decisions about the organs donated.

The Potential of Repairing Ischemically Damaged Human Kidneys during Acellular Warm Perfusion

Introduction In previous work we demonstrated the feasibility of resuscitating oxidative metabolism of sufficient magnitude to result in restored synthetics functions in kidney allografts with as much as 2H of warm ischemic (WI) injury during an acellular warm perfusion. The restored synthetic functions lead to modulation of both injury and repair proteins in the damaged kidneys. We now report that a longer period of ex vivo warm perfusion of human DCD kidneys results in a more extensive regeneration as revealed by the observation of actual mitosis in the repairing human kidneys by 48H of warm perfusion (Figure 1). We also evaluated whether a Mesenchymal Stem/Stromal Cell (MSC) therapy could accelerate this active reparative process in the ischemically damaged human kidneys during the ex vivo warm perfusion. We hypothesized that by administering MSC directly to the renal tissue, there would be an improved opportunity for cellular repair mediated by the increased intrarenal paracrine effects. Methods The studies were performed using the Exsanguinous Metabolic Support (EMS) platform. Paired human kidney allografts from DCD donors (mean WI of 30 min with unknown down time in 2) were studied. Kidneys were EMS perfused with or without the addition of MSC (1x10^8). The kidneys were evaluated by histological grading, cytokine/chemokine synthesis and a panel of biomarkers indicative of DNA synthesis and cytoskeletal regeneration. Results The period of warm perfusion led to a significant increase in the synthesis of ATP and growth factors resulting in normalization of metabolism and the cytoskeleton during ex vivo perfusion. The addition of a MSC treatment led to a further reduction in the synthesis of inflammatory cytokines as well as an increase in the synthesis of growth factors that are associated with renal regeneration (Table 1). Toluidine Blue staining of MSC treated kidneys demonstrated a significant increase in the number of renal cells undergoing mitosis (23%) compared to EMS perfusion alone (Figure 1). Discussion To our knowledge, our work is the first to have achieved actual cellular regeneration while ischemically damaged human kidneys are perfused ex vivo for several days. The observation of increased growth factor synthesis is significant because the polypeptides are known to potentiate kidney function and have been shown to play an important role in vivo for the recovery of function following renal damage.Conclusion The observed regeneration entails: increased synthesis of ATP, reduced inflammatory response, increased synthesis of growth factors, normalization of the cytoskeleton and mitosis. The added treatment of administering MSCs further potentiated the renal repair. The ability to regenerate renal tissue ex vivo sufficiently to result in immediate function could revolutionize transplantation by helping to address the chronic organ shortage. National Institute of Health - NIAID Grant # R43AI06362.

Urinary TIMP-2 predicts the presence and duration of delayed graft function in DCD kidney transplant recipients

Urinary TIMP-2 predicts the presence and duration of delayed graft function in DCD kidney transplant recipients

Outcomes of EC-MPS combined with low-dose tacrolimus in DCD kidney transplantation for high-risk DGF recipients

Effective use of immunosuppressive agents to avoid the occurrence of nephrotoxicity and rejection in recipients with delayed graft function (DGF) is a concern for physicians. We investigated the outcomes of treatment with enteric-coated mycophenolate sodium (EC-MPS) in combination with a low-dose of tacrolimus (Tac) in renal transplantation for recipients with a high risk of DGF. We conducted a retrospective study of 61 recipients with a high risk of DGF who were treated with EC-MPS and low-dose Tac. The recipients were separated into a no-DGF group and a DGF group, based on whether DGF actually occurred. The results showed that although EC-MPS and Tac doses were similar in both groups, the percentage of recipients whose mycophenolic acid area under the curve 0–12 h (MPA-AUC0–12 h) was below 30 (mg·h)/L was significantly higher and the Tac trough concentration significantly lower in the DGF group one week after transplantation. Notably, a higher incidence of biopsy-proven acute rejection (BPAR) was found in the DGF group and among all recipients whose MPA-AUC0–12 h was less than 30 (mg·h)/L at one week after transplantation. One-year graft survival, patient survival, allograft function, and the incidence of the most common adverse events were similar in the two groups. In conclusion, the immunosuppressive regime is applicable to Chinese kidney transplant recipients, and early low exposure to EC-MPS was related to acute rejection in the recipients at a high risk of DGF.

PD25-01 KIDNEY PRESERVATION TECHNIQUES IN CONTROLLED CIRCULATORY DEATH: NECMO AND ULTRA-RAPID RETRIEVAL

You have accessJournal of UrologyTransplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery I1 Apr 2018PD25-01 KIDNEY PRESERVATION TECHNIQUES IN CONTROLLED CIRCULATORY DEATH: NECMO AND ULTRA-RAPID RETRIEVAL Begoña Etcheverry Giadrosich, Maria Fiol Riera, Lluis Riera Canals, Sergi Beato García, José Francisco Suárez Novo, Salvador Gil-Vernet Cebrian, and Francesc Vigués Julià Begoña Etcheverry GiadrosichBegoña Etcheverry Giadrosich More articles by this author , Maria Fiol RieraMaria Fiol Riera More articles by this author , Lluis Riera CanalsLluis Riera Canals More articles by this author , Sergi Beato GarcíaSergi Beato García More articles by this author , José Francisco Suárez NovoJosé Francisco Suárez Novo More articles by this author , Salvador Gil-Vernet CebrianSalvador Gil-Vernet Cebrian More articles by this author , and Francesc Vigués JuliàFrancesc Vigués Julià More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1328AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES During the past decade, kidneys obtained after controlled circulatory death (cDCD) have significantly increased, in order to increase the number of donors. It achieved 24% of total Kidneys transplant during the last year in Spain. However, it implies warm ischemia times, resulting a greater risk for organs. Focusing on graft quality optimization, it has implemented the abdominal Normothermic Extracorporeal Membrane Oxygenation (NECMO) in order to restore blood flow before organ recovery. NECMO perfusion provides promising results for the use of liver grafts for cDCD. The aim of this study is to evaluate cDCD kidneys, obtained from NECMO technique compared with cDCD ultra-rapid retrieval. METHODS We perform a case control study of Maastricht category III DCD kidneys transplanted in one single center, Hospital Universitari de Bellvitge, Barcelona. We compared kidneys of both cDCD ultra-rapid retrieval and NECMO retrieval groups. RESULTS From 2013 to 2017, 109 kidneys transplants from Maastricht category III DCD donors were performed. Out of these, 76% (83) were retrieved from our hospital and the remaining 24% (26), came from other centers. Mean age was 63 years old (CI95%: 61-65), 42% (63) were no-EDC (extended donor criteria) We compared 2 groups: ultra-rapid retrieval versus NECMO retrieval for non-EDC Masstricht category III CDC (data is presented in table 1). From multivariable analysis, NECMO is associated with less DGF than Ultra-rapid retrieval, OR 0.19 (IC95%: 0.038-0.96, p= 0.044). CONCLUSIONS Although the Ultra-rapid retrieval is highly extended with satisfactory results, in our series kidney preservation with NECMO shows less DGF, corroborating that it could be a good way to reverse warm ischemia effects. We have better kidney function in the follow-up. However, it is a small sample, and we need more follow-up. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e545-e546 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Begoña Etcheverry Giadrosich More articles by this author Maria Fiol Riera More articles by this author Lluis Riera Canals More articles by this author Sergi Beato García More articles by this author José Francisco Suárez Novo More articles by this author Salvador Gil-Vernet Cebrian More articles by this author Francesc Vigués Julià More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Early Outcomes of the New UK Deceased Donor Kidney Fast-Track Offering Scheme.

The UK Kidney Fast-Track Scheme (KFTS) was introduced in 2012 to identify kidneys at high risk of discard and to rapidly facilitate transplantation. A retrospective analysis of kidneys transplanted through the KFTS was undertaken. UK Transplant Registry data were collected on deceased donor kidneys implanted between November 1, 2012, and April 30, 2015, (donation after brain death [DBD] donors) and March 1, 2013, and April 30, 2015 (donation after circulatory death [DCD] donors). Posttransplant outcomes included 1-year estimated glomerular filtration rate and death-censored graft survival (DCGS). Over the study period, 523 deceased donor kidneys were transplanted through the KFTS and 4174 via the standard National Kidney Allocation Scheme (NKAS). Kidneys in the KFTS were more likely to be from older diabetic donors, had a higher frequency of poor ex vivo perfusion, had longer cold ischemic times, and were transplanted into older recipients. One-year DCGS of KFTS and NKAS DBD donor kidneys was similar (94% vs 95%; P = 0.70), but for DCD donor kidneys, DCGS was lower in those allocated via the KFTS (91% versus 95%; P = 0.04). Median 1-year estimated glomerular filtration rate for DBD donor kidneys was lower in those allocated via the KFTS (49 vs 52 mL/min per 1.73 m; P = 0.01), but for DCD kidneys, there was no difference (45 vs 48 mL/min per 1.73 m; P = 0.10). Although KFTS kidneys have less favorable donor, graft, and recipient risk factors than NKAS kidneys, short-term graft and patient outcomes are acceptable. National schemes that identify and rapidly offer kidneys at high risk of discard may contribute to minimizing the unnecessary discard of organs.

The duration of asystolic ischemia determines the risk of graft failure after circulatory-dead donor kidney transplantation: A Eurotransplant cohort study.

Circulatory death donor (DCD) kidney transplantations are steadily increasing. Consensus reports recommend limiting donor warm ischemia time (DWIT) in DCD donation, although an independent effect on graft outcome has not been demonstrated. We investigated death-censored graft survival in 18065 recipients of deceased-donor kidney transplants in the Eurotransplant region: 1059 DCD and 17006 brain-dead donor (DBD) kidney recipients. DWIT was defined as time from circulatory arrest until cold flush. DCD donation was an independent risk factor for graft failure (adjusted hazard ratio [HR] 1.28, 95% CI 1.10-1.46), due to an increased risk of primary nonfunction (62/1059 vs 560/17006; P<.0001). With DWIT in the model, DCD donation was no longer a risk factor, demonstrating that DWIT explains the inferior graft survival of DCD kidneys. Indeed, DCD transplants with short DWIT have graft survival comparable to that of standard-criteria DBD transplants (P=.59). DWIT also associated with graft failure in DCDs (adjusted HR 1.20 per 10-minute increase, 95% CI 1.03-1.42). At 5years after transplantation, graft failure occurred in 14 of 133 recipients (10.5%) with DWIT <10minutes, 139 of 555 recipients (25.0%) with DWIT between 10 and 19minutes, and 117 of 371 recipients (31.5%) with DWIT ≥20minutes. These findings support the expert opinion-based guidelines to limit DWIT.

CD47 blockade reduces ischemia/reperfusion injury in donation after cardiac death rat kidney transplantation.

Modulation of nitric oxide activity through blockade of CD47 signaling has been shown to reduce ischemia-reperfusion injury (IRI) in various models of tissue ischemia. Here, we evaluate the potential effect of an antibody-mediated CD47 blockade in a syngeneic and an allogeneic DCD rat kidney transplant model. The donor organ was subjected to 1hour of warm ischemia time after circulatory cessation, then flushed with a CD47 monoclonal antibody (CD47mAb) in the treatment group, or an isotype-matched immunoglobulin in the control group. We found that CD47mAb treatment improved survival rates in both models. Serum markers of renal injury were significantly decreased in the CD47mAb-treated group compared with the control group. Histologically the CD47mAb-treated group had significantly reduced scores of acute tubular injury and acute tubular necrosis. The expression of biomarkers related to mitochondrial stress and apoptosis also were significantly lower in the CD47mAb-treated groups. Overall, the protective effects of CD47 blockade were greater in the syngeneic model. Our data show that CD47mAb blockade decreased the IRI of DCD kidneys in rat transplant models. This therapy has the potential to improve DCD kidney transplant outcomes in the human setting.

経皮的心肺補助（PCPS）装着心停止ドナーから長期間保存した献腎移植の一例

経皮的心肺補助（PCPS）装着心停止ドナーから長期間保存した献腎移植の一例

Outcome Improvement for Hypothermic Machine Perfusion Versus Cold Storage for Kidneys From Cardiac Death Donors.

Organ shortage has led to an increased use of kidneys from cardiac death donors (DCDs), but controversies about the methods of organ preservation still exist. This study aims to compare the effect of machine perfusion (MP) and cold storage (CS) in protecting kidneys harvested from DCDs. 141 kidney pairs from DCDs between July 2010 and July 2015 were included in this randomized controlled study. One kidney from each donor was randomly assigned to MP and the contralateral kidney was assigned to CS. Delayed graft function (DGF) rate, resistance index of renal arteries, early renal function, and survival rates were used to estimate the effect of preservation. The results showed that MP decreased the rate of DGF from 33.3 to 22.0% (P = 0.033). Ultrasound of the kidneys within 48 h after transplantation showed that the resistance index of renal main artery (0.673 ± 0.063 vs. 0.793 ± 0.124, P < 0.001), sub segmental artery (0.66 ± 0.062 vs. 0.764 ± 0.077, P < 0.001) and interlobular artery (0.648 ± 0.056 vs. 0.745 ± 0.111, P = 0.023) were all significantly lower in the MP group than those in the CS group. Furthermore, compared to the CS group, in the first 7 days following transplantation, the median urine volume was significantly higher (4080 mL vs. 3000 mL, P = 0.047) in kidneys sustained using MP and the median serum creatinine was remarkably lower (180 µmol/L vs. 390 µmol/L, P = 0.024). More importantly, MP group had higher 1- and 3-year graft survival rates (98% vs. 93%, P = 0.026; 93% vs. 82%, P = 0.036, respectively). Hypothermic MP improved the outcomes of DCD kidney transplantation.

Supplemental oxygen during hypothermic kidney preservation: A systematic review.

We reviewed the evidence for ex-vivo Supplemental Oxygen during Hypothermic preservation (SOH) for deceased donor kidneys. Bibliographic databases were searched for human and animal studies of SOH in kidney transplantation reporting on patient or animal survival rate, discard rate, technical complications or renal function outcomes. We make special reference to a specific subgroup: supplemental oxygen applied during cold perfusion, referred to as Hypothermic Oxygenated Perfusion (HOP). Four human and 25 animal studies were identified. The data present conflicting results but suggest that the effects of oxygen on restoring kidney function during preservation may be of value for DCD kidneys and/or kidneys that have undergone a period of hypotension, warm ischemia or poor perfusion in the donor. There is very little information available from human or animal studies. This work highlights to the transplant community that far more high quality clinical studies are required to understand this technology and its role before widespread clinical introduction.

Abdominal regional in-situ perfusion in donation after circulatory determination of death donors.

Provide an overview regarding the current state of abdominal regional perfusion (ARP) in donation after circulatory determination of death (DCD) organ transplantation, including the principles behind how ARP functions and the most recent results of its clinical application. ARP has been applied clinically in DCD at both hypothermic and normothermic temperatures. The use of hypothermic perfusion has primarily been limited to DCD kidney transplantation, whereas normothermic regional perfusion has been used to improve and assess the quality of DCD kidneys, livers, and even a handful of pancreata for transplantation. Results of recent single-center series reflect acceptable rates of early graft function and survival using grafts that might have otherwise been discarded. ARP is an important form of donor maintenance that helps improve DCD organ viability and may help expand the applicability of transplantation using organs arising through this process.

Successful Transplantation of Kidneys From Elderly Circulatory Death Donors by Using Microscopic and Macroscopic Characteristics to Guide Single or Dual Implantation

Most kidneys from potential elderly circulatory death (DCD) donors are declined. We report single center outcomes for kidneys transplanted from DCD donors over 70 years old, using preimplantation biopsy Remuzzi grading to inform implantation as single or dual transplants. Between 2009 and 2012, 43 single transplants and 12 dual transplants were performed from elderly DCD donors. Remuzzi scores were higher for dual than single implants (4.4 vs. 3.4, p < 0.001), indicating more severe baseline injury. Donor and recipient characteristics for both groups were otherwise similar. Early graft loss from renal vein thrombosis occurred in two singly implanted kidneys, and in one dual-implanted kidney; its pair continued to function satisfactorily. Death-censored graft survival at 3 years was comparable for the two groups (single 94%; dual 100%), as was 1 year eGFR. Delayed graft function occurred less frequently in the dual-implant group (25% vs. 65%, p = 0.010). Using this approach, we performed proportionally more kidney transplants from elderly DCD donors (23.4%) than the rest of the United Kingdom (7.3%, p < 0.001), with graft outcomes comparable to those achieved nationally for all deceased-donor kidney transplants. Preimplantation biopsy analysis is associated with acceptable transplant outcomes for elderly DCD kidneys and may increase transplant numbers from an underutilized donor pool.

Evolution of Renal Transplant Practice Over the Past Decade: A U.K. Center Experience

ObjectiveAs renal transplantation continues to evolve, there appears to be a change in both donor and recipient populations. Traditional markers of high-risk donor (e.g. donation after cardiac death [DCD]/expanded criteria donor [ECD]) and recipient (e.g. obese, highly sensitized) operations appear to be more common without any noticeable worsening of patient outcome. The present study aimed to compare outcome and define the change in donor and recipient populations for cadaveric transplants over a 10-year period at a large U.K. center. MethodsSingle-center analysis of all adult patients undergoing cadaveric renal transplantation between January 2004 and January 2014 (n = 754). Transplants were divided into 3 groups (early, middle, and late) depending on the era, with donor, recipient and outcomes compared. ResultsThere were considerable changes in both donor and recipient factors between the 3 eras, with a greater proportion of high-risk operations performed, as reflected by significant increases in Donor Risk Index (median: 1.11–1.16, P = .022), and the proportions of ECD (22.2%–33.9%, P = .003) and DCD kidneys (10.8%–19.4% P = .011). However, 1-year graft survival was comparable between the eras, with a decrease in the average 1-year serum creatinine between the early and late cohort (median: 161 μmol/L vs 132 μmol/L, P < .001). There was no significant increase in body mass index (BMI) in either the donor or recipient population across the eras. ConclusionImprovement in transplant outcome continues despite a greater proportion of transplants previously considered as high risk being performed. This is likely to reflect a considerable improvement in pre- and postoperative management. BMI remains a major continuing block to transplantation.