Renal Resistance Trend During Hypothermic Machine Perfusion Is More Predictive of Postoperative Outcome Than Biopsy Score: Preliminary Experience in 35 Consecutive Kidney Transplantations

Hypothermic machine perfusion (HPM) grants a better postoperative outcome in transplantation of organs procured from extended criteria donors (ECDs) and donors after cardiac death (DCD). So far, the only available parameter for outcome prediction concerning those organs is pretransplant biopsy score. The aim of this study is to evaluate whether renal resistance (RR) trend during HPM may be used as a predictive marker for post‐transplantation outcome. From December 2015 to present, HMP has been systematically applied to all organs from ECDs and DCD. All grafts underwent pretransplantation biopsy evaluation using Karpinski's histological score. Only organs that reached RR value ≤1.0 within 3 hours of perfusion were transplanted. Single kidney transplantation (SKT) or double kidney transplantation (DKT) were performed according to biopsy score results. Sixty‐five HMPs were performed (58 from ECDs and 7 from DCD/ECMO donors). Fifteen kidneys were insufficiently reconditioned (RR > 1) and were therefore discarded. Forty‐nine kidneys were transplanted, divided between 21 SKT and 14 DKT. Overall primary nonfunction (PNF) and delayed graft function (DGF) rate were 2.9 and 17.1%, respectively. DGF were more common in kidneys from DCD (67 vs. 7%; P = 0.004). Biopsy score did not correlate with PNF/DGF rate (P = 0.870) and postoperative creatinine trend (P = 0.796). Recipients of kidneys that reached RR ≤ 1.0 within 1 hour of HMP had a lower PNF/DGF rate (11 vs. 44%; P = 0.033) and faster serum creatinine decrease (POD10 creatinine: 1.79 mg/dL vs. 4.33 mg/dL; P = 0.019). RR trend is more predictive of post‐transplantation outcome than biopsy score. Hence, RR trend should be taken into account in the pretransplantation evaluation of the organs.     

Evaluation of outcomes in renal transplantation with hypothermic machine perfusion for the preservation of kidneys from expanded criteria donors

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.     

Mechanisms of Hypothermic Machine Perfusion to Decrease Donation After Cardiac Death Graft Inflammation: Through the Pathway of Upregulating Expression of KLF2 and Inhibiting TGF‐β Signaling

Hypothermic machine perfusion (HMP) has been known as an efficient way to improve kidney graft function, but the underlying mechanisms remain unclear. Here, we adopt a rabbit reperfusion mode to investigate the upstream mechanisms of end‐ischemic HMP of kidneys from donors after cardiac death (DCD), with static cold storage (CS) as a control. Eighteen New Zealand healthy male rabbits (12 weeks old, with a weight of 3.0 ± 0.2 kg) were randomly divided into three groups: HMP group, CS group, and Normal group (n = 6). The left kidney of rabbits underwent warm ischemia for 25 min through clamping the left renal pedicle and then reperfusion for 1 h. Then the left kidneys were preserved by CS or HMP (4°C for 4 h) ex vivo respectively, after they were autotransplanted and rabbits were submitted to a right nephrectomy. Twenty‐four hours after reperfusion, all left renal specimens were collected. Finally, the expression of Krüppel‐like factor 2 (KLF2), transforming growth factor‐β (TGF‐β) and SMAD4 protein in renal cortical tissue were detected by immunoblotting, and the TGF‐β and SMAD4 expressions were further confirmed by immunohistochemistry analysis. We found that expression of KLF2 in HMP group was significantly higher than CS group (P = 0.011), while expression of TGF‐β and SMAD4 in HMP group were significantly lower than CS group (P = 0.002, P = 0.01, respectively); Compared with normal group, the expression of TGF‐β and SMAD4 in HMP and CS group significantly increased (P<0.05). Compared with CS group, TGF‐β and SMAD4 protein were equally down‐regulated in glomerular and the tubular epithelial cells in HMP group confirmed by immunohistochemistry. In conclusion, HMP may decrease DCD kidneys inflammation through the pathway of upregulating expression of KLF2 and inhibiting TGF‐β signaling after transplantation.     

LifePort保存心脏死亡器官捐献供肾的临床研究

目的:探讨采用LifePort保存心脏死亡器官捐献(DCD)供肾对移植肾功能恢复的影响。方法:分析解放军三〇三医院2012年8月~2013年10月期间30个DCD案例肾移植后受者的临床资料。根据同一供体两只供肾采用不同的保存方式,随机分入LifePort组(n=30)和普通冷藏组(n=30例),比较两组受者肾功能恢复延迟(DGF)、急性排斥反应(AR)等并发症的发生率及移植肾功能恢复等情况。结果:LifePort组受者的DGF发生率为20%(6/30),而普通冷藏组的DGF发生率为46.7%(14/30),差异有统计学意义(P0.05)。两组间AR发生率、围手术期移植肾存活率及受者存活率的差异无统计学意义(P0.05)。LifePort组受者术后出院时血清肌酐恢复优于普通冷藏组,且平均住院时间较短,差异有统计学意义(P0.05)。结论:LifePort能有效改善离体DCD供肾的保存质量,降低受者DGF发生率,有利于移植肾功能恢复。     

One‐year results of a prospective,randomized trial comparing two machine perfusion devices used for kidney preservation

Studies have shown beneficial effects of machine perfusion (MP) on early kidney function and long‐term graft survival. The aim of this study was to investigate whether the type of perfusion device could affect outcome of transplantation of deceased donor kidneys. A total of 50 kidneys retrieved from 25 donors were randomized to machine perfusion using a flow‐driven (FD) device (RM3; Waters Medical Inc) or a pressure‐driven (PD) device (LifePort; Organ Recovery Systems), 24 of these kidneys (n = 12 pairs; 48%) were procured from expanded criteria donors (ECD). The primary endpoints were kidney function after transplantation defined using the incidence of delayed graft function (DGF), the number of hemodialysis sessions required, graft function at 12 months, and analyses of biopsy. DGF was similar in both groups (32%; 8/25). Patients with DGF in the FD group required a mean of 4.66 hemodialysis sessions versus 2.65 in the PD group (P = 0.005). Overall, 1‐year graft survival was 80% (20/25) vs. 96% (24/25) in the FD and PD groups. One‐year graft survival of ECD kidneys was 66% (8/12) in the FD group versus 92% (11/12) in the PD group. Interstitial fibrosis and tubular atrophy were significantly more common in the FD group – 45% (5/11) vs. 0% (0/9) (P = 0.03) in PD group. There were no differences in creatinine levels between the groups. Machine perfusion using a pressure‐driven device generating lower pulse stress is superior to a flow‐driven device with higher pulse stress for preserving kidney function.     

Risk stratification of kidneys from donation after cardiac death donors and the utility of machine perfusion

Cantafio AW, Dick AAS, Halldorson JB, Bakthavatsalam R, Reyes JD, Perkins JD. Risk stratification of kidneys from donation after cardiac death donors and the utility of machine perfusion.
Clin Transplant 2011: 25: E530–E540. © 2011 John Wiley & Sons A/S. Abstract: There has been a dramatic increase in the utilization of kidneys from donors after cardiac death (DCD). While these organs represent an opportunity to expand the donor pool, the assessment of risk and optimal perioperative management remains unclear. Our primary aim was to identify risk factors for objective outcomes, and secondarily, we sought to determine what impact pulsatile machine perfusion (PMP) had on these outcomes. From 1993 to November 2008, 6057 DCD kidney transplants were reported to the Organ Procurement and Transplantation Network database, with complete endpoints for delayed graft function (DGF) and graft survival (GS). Risk factors were identified using a multivariable regression analysis adjusted for recipient factors. Age (50 yr) [OR 1.81, p < 0.0001] and cold ischemia time (CIT) (>30 h) [OR 3.22, p < 0.0001] were the strongest predictors of DGF. The use of PMP decreased the incidence of DGF only when donor age was >60 yr and improved long‐term graft survival when donor age was >50 yr. Donor warm ischemia time >20 min was also found to correlate with increased DGF. While the incidence of DGF in DCD kidneys is significantly higher, the only factors the transplant surgeon can control are CIT and the use of PMP. The data suggest that the use of PMP in DCD kidneys <50 yr old provides little clinical benefit and may increase CIT.     

Hypothermic Machine Perfusion Versus Static Cold Storage in Deceased Donor Kidney Transplantation: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

Static cold storage (SCS) and hypothermic machine perfusion (HMP) are two primary options for renal allograft preservation. Compared with SCS, HMP decreased the incidence of delayed graft function (DGF) and protected graft function. However, more evidence is still needed to prove the advantages of the HMP. In this study, the outcomes of kidney grafts from the two preservation methods were compared by conducting a systematic review and meta‐analysis. Randomized controlled trials (RCTs) comparing the effect of hypothermic machine perfusion and static cold storage in deceased donor kidney transplantation were identified through searches of the MEDLINE, EMBASE, and Cochrane databases between January 1, 1980 and December 30, 2017. The primary endpoints were delayed graft function and graft survival. Secondary endpoints included primary non‐function (PNF), graft renal function, duration of DGF, acute rejection, postoperative hospital stay and patient survival. Summary effects were calculated as risk ratio (RR) with 95% confidence interval (CI) or mean difference (MD) with 95% confidence intervals (CI). A total of 13 RCTs were included, including 2048 kidney transplant recipients. The results indicated that compared with SCS, HMP decreased the incidence of DGF (RR 0.78, 95% CI 0.69–0.87, P < 0.0001), and improved the graft survival at 3 years (RR 1.06, 95% CI 1.02–1.11, P = 0.009). There was no significant difference in other endpoints. HMP might be a more desirable method of preservation for kidney grafts. The long‐term outcomes of kidney allografts stored by hypothermic machine perfusion still need to be further investigated.     

Donor kidney disease and transplant outcome for kidneys donated after cardiac death

Background:

Although outcomes of kidney transplants following donation after cardiac death (DCD) and donation after brainstem death (DBD) are similar, generally only optimal younger DCD donors are considered. This study examined the impact of pre‐existing donor kidney disease on the outcome of DCD transplants.

Methods:

This retrospective study compared the outcome of all DCD kidney transplants performed during 1996–2006 with contemporaneous kidney transplants from DBD donors. Implantation biopsies were scored for glomerular, tubular, parenchymal and vascular disease (global histology score). There were 104 DCD and 104 DBD kidney transplants.

Results:

Delayed graft function (DGF) occurred more frequently in DCD than DBD kidneys (64·4 versus 28·8 per cent; P < 0·001). Long‐term graft outcome was similar. The only donor factor that influenced outcome was baseline kidney disease, which was similar in both groups, even though DCD donors were younger, with a higher predonation estimated glomerular filtration rate. The global histology score predicted DGF (odds ratio 1·85 per unit; P = 0·006) and graft failure (relative risk 1·55 per unit; P = 0·001), although there was no difference for DCD and DBD kidneys.

Conclusion:

Transplant outcomes for DCD and DBD kidneys are comparable. Baseline donor kidney disease influences DGF and graft survival but the impact is no greater for DCD kidneys. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.     

Cold Machine Perfusion Versus Static Cold Storage of Kidneys Donated After Cardiac Death: A UK Multicenter Randomized Controlled Trial

One third of deceased donor kidneys for transplantation in the UK are donated following cardiac death (DCD). Such kidneys have a high rate of delayed graft function (DGF) following transplantation. We conducted a multicenter, randomized controlled trial to determine whether kidney preservation using cold, pulsatile machine perfusion (MP) was superior to simple cold storage (CS) for DCD kidneys. One kidney from each DCD donor was randomly allocated to CS, the other to MP. A sequential trial design was used with the primary endpoint being DGF, defined as the necessity for dialysis within the first 7 days following transplant. The trial was stopped when data were available for 45 pairs of kidneys. There was no difference in the incidence of DGF between kidneys assigned to MP or CS (58% vs. 56%, respectively), in the context of an asystolic period of 15 min and median cold ischemic times of 13.9 h for MP and 14.3 h for CS kidneys. Renal function at 3 and 12 months was similar between groups, as was graft and patient survival. For kidneys from controlled DCD donors (with mean cold ischemic times around 14 h), MP offers no advantage over CS, which is cheaper and more straightforward.     

Hypothermic Machine Perfusion as an Alternative to Biopsy Assessment in Transplantation of Kidneys Donated After Cardiocirculatory Death: A Pilot Study

BackgroundTransplantation of kidneys from donation after cardiocirculatory death (DCD) donors is becoming an ever-increasing reality. So far, biopsy histologic assessment is the main parameter for evaluation of graft suitability, but it has several drawbacks and has poor reliability. The aim of this study is to verify if real-time renal resistance (RR) measurement during hypothermic machine perfusion (HMP) can be used as a reliable parameter to evaluate the quality of grafts from DCD and extracorporeal membrane oxygenation (ECMO) donors.MethodsFrom January 2015 to September 2018, HMP has been systematically applied to all organs from DCD and ECMO donors. All grafts underwent preimplantation biopsy histologic assessment with Karpinski’s score. Single kidney transplants (SKTs) or double kidney transplants (DKTs) were performed according to biopsy score results. Kidneys were considered suitable for transplant if RR reached ≤ 1.0 within 3 hours of perfusion. RR trend and postoperative outcome were analyzed considering biopsy score and donor type.ResultsA total of 30 kidneys (15 from DCD and 15 from ECMO donors) were used to perform 26 transplants (22 SKTs and 4 DKTs). Considering RR trend, all grafts were considered suitable for transplant within 1 hour of perfusion. Biopsy confirmed this result in all cases, and median score was 3 (range, 0-7). SKT score kidneys had lower starting RR than DKT ones (1.88 vs 2.88; P = .04) but identical final RR (0.58 vs 0.57; P = .76). DKT recipients had faster postoperative creatinine reduction than SKT recipients but similar postoperative day 30 value (1.42 vs 1.15 mg/dL; P = .20). No differences were found between DCD and ECMO grafts in terms of RR trend and postoperative outcome.ConclusionsHMP can be an alternative to histologic biopsy assessment for evaluation of transplant suitability of DCD and ECMO kidneys. If acceptability threshold is reached, SKT can be performed in all cases. ECMO donors should be considered like DCD donors.     

Perfusion Parameters of Donation After Cardiac Death Kidneys Predict Early Transplant Outcomes Based on Expanded Criteria Donor Designation

Background

Donation after cardiac death is the only source of the deceased donor in China at present. Hypothermic machine perfusion has been used increasingly over the years. We determined the hypothermic machine perfusion parameters associated with early transplant outcomes based on the expanded criteria donor (ECD) designation.

Experience in renal and extrarenal transplantation with donation after cardiac death donors with selective use of extracorporeal support

BACKGROUND: Most reports of donation after cardiac death (DCD) donors are exclusive to kidney transplantation and report high rates of delayed graft function (DGF). STUDY DESIGN: From April 1, 2003, to October 3, 2007, we performed 53 kidney transplantations and 4 simultaneous kidney-pancreas transplantations from DCD donors. All DCD donor kidneys were managed with pulsatile perfusion preservation, and all simultaneous kidney-pancreas transplantation donors were managed with extracorporeal support. RESULTS: Of 53 DCD kidney transplantations, 44 (83%) were from standard criteria donors (SCD) and 9 (17%) from expanded criteria donors (ECD). With a mean followup of 12 months, actual patient and kidney graft survival rates were 94% and 87%, respectively. Patient and graft survival rates were 100% in the 4 simultaneous kidney-pancreas transplantations. Incidence of DGF was 57% (60% without versus 20% with extracorporeal support, p = 0.036). Comparison of the 53 DCD donor kidney transplantations with 316 concurrent donation after brain death (DBD) donor adult kidney transplantations (178 SCD, 138 ECD) revealed no differences in demographics or outcomes, except that the DCD donor group had fewer ECDs (17% DCD versus 44% DBD; p = 0.0002), fewer 0-antigen mismatch kidney transplantations (7.5% DCD versus 19% DBD; p = 0.05), and more kidneys preserved with pulsatile perfusion (100% DCD versus 52% DBD; p < 0.0001). Incidences of DGF (57% DCD versus 19% DBD; p < 0.0001) and acute rejection (19% DCD versus 10% DBD; p = 0.10) were higher in the DCD donor group, which resulted in a longer initial length of stay (mean 11 days DCD versus 8.0 days DBD; p = 0.006). CONCLUSIONS: Despite a high incidence of DGF in the absence of extracorporeal support and greater initial resource use, comparable short-term results can be achieved with DCD and DBD donor kidney transplantations.     

Hypothermic Machine Perfusion Decreases Renal Cell Apoptosis During Ischemia/Reperfusion Injury via the Ezrin/AKT Pathway

This study aimed to explore the potential mechanisms of hypothermic machine perfusion (HMP)—a more efficient way to preserve kidneys from donors after cardiac death than static cold storage (CS), then to provide the basis for further improving donor quality. Twelve healthy male New Zealand rabbits (12 weeks old, weighing 3.0 ± 0.3 kg) were randomly divided into two groups: the HMP group and CS group (n = 6). Rabbits’ left kidney was subjected to 35 min of warm ischemic time by clamping the left renal pedicle and 1 h of reperfusion. The kidneys were then hypothermically (4–8°C) preserved in vivo for 4 h with HCA‐II solution using HMP or CS methods. Then rabbits underwent a right nephrectomy and the kidney tissues were collected after 24 h of reperfusion. TUNEL staining was performed on paraffin sections to detect apoptosis, and the expressions of cleaved caspase‐3, ezrin, AKT, and p‐AKT in frozen kidney tissues were detected by Western blotting. The ezrin expression was further confirmed by immunohistochemistry analysis. The apoptosis rate and expression of cleaved caspase‐3 in the HMP group were significantly lower than the CS group (P < 0.001 and P = 0.002), meanwhile the expression of cleaved caspase‐3 in the HMP and CS groups was significantly increased compared with the normal group (P = 0.035 and P < 0.001), and the expression of ezrin and p‐AKT in the HMP group was significantly higher than the CS group (P = 0.005, 0.014). HMP decreased the renal cell apoptosis rate during ischemia/reperfusion injury via the ezrin/AKT pathway.     

Outcomes of donation after circulatory death kidneys undergoing hypothermic machine perfusion following static cold storage: A UK population‐based cohort study

Evidence is currently lacking regarding the outcomes of kidneys undergoing hypothermic machine perfusion (HMP) in patients in the United Kingdom. Using the National Health Service Blood and Transplant database, the authors compared outcomes for recipients of single‐organ donation after circulatory death (DCD) kidneys preserved with HMP with those preserved using only static cold storage (SCS). Between 2007 and 2015, HMP was used in 19.1% (864/4,529) of kidneys. Rates of delayed graft function (DGF) were significantly lower in organs preserved with HMP than for organs preserved with SCS (34.2% vs 42.0%, P < .001), despite a slightly longer cold ischemic time (median: 14.8 vs 14.1 hours, P < .001). Multivariable analysis found the effect of preservation modality to remain significant, with HMP organs having a significantly lower rate of DGF (odds ratio 0.65, 95% confidence interval 0.53‐0.80, P < .001) and significantly shorter times to DGF resolution (average: 6.1 vs 7.4 days, P = .003) than SCS organs. The patient (P = .313) and graft (P = .263) survival rates were similar in the 2 preservation groups. HMP was associated with a marginal functional benefit in 1‐year creatinine values (P = .044), with adjusted averages of 1.36 mg/dL (HMP) versus 1.40 mg/dL (SCS). This study supports the use of HMP and aids decision‐making over its instigation, which may improve short‐term patient outcomes.     

Hypothermic Machine Perfusion Reduced Inflammatory Reaction by Downregulating the Expression of Matrix Metalloproteinase 9 in a Reperfusion Model of Donation After Cardiac Death

The exact mechanism by which hypothermic machine perfusion (HMP) improves the graft quality in kidney transplantation of donation after cardiac death (DCD) remains unclear. The aim of this study was to investigate the correlation between the expression of matrix metalloproteinase 9 (MMP‐9) and inflammatory reaction in kidney ischemia‐reperfusion (I/R) injury injury followed by cold storage (CS) or HMP model of DCD. New Zealand white rabbit kidneys were subjected to 35 min of warm ischemia and 1 h reperfusion, then preserved by either 1 h reperfusion (sham‐operated group), 4 h CS or 4 h HMP in vivo. Kidneys were reperfused 24 h followed by further analysis. No treatment was given to rabbits in the normal control group. The expression of MMP‐9, nuclear factor‐κB (NF‐κB), and MMP‐2 mRNA were detected by real‐time PCR (RT‐PCR). MMP‐9 was located by immunohistochemistry and immunofluorescence methods. Tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), myeloperoxidase (MPO), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured by kits for each groups. Compared with the CS group, the expression of MMP‐9 and NF‐κB mRNA were downregulated in HMP group (P < 0.05). In contrast, expression of MMP‐2 mRNA had no statistical significance between CS group and HMP group (P > 0.05). In normal control and sham‐operated groups, a low level of MMP‐9 expression was detected in glomeruli. However, positive signals of MMP‐9 were mostly located in the tubulointerstitium and the vascular wall of CS and HMP groups. Expression of TNF‐α, IL‐6, MDA, and activity of MPO decreased while activity of SOD in the HMP group increased in contrast to the CS group (P < 0.05). In conclusion, inflammatory cytokines mediated MMP‐9 expression through NF‐κB band to MMP‐9 promoter region, resulting in renal injury. Therefore, HMP reduced inflammatory reaction by downregulating the expression of MMP‐9, which may be the mechanism of kidney protection in I/R injury.     

MicroRNA‐21 (miR‐21) expression in hypothermic machine perfusate may be predictive of early outcomes in kidney transplantation

Hypothermic machine perfusion is effective in improving outcome following kidney transplantation. Molecular analyses of hypothermic machine perfusate (HMP) have the potential to identify biomarkers of organ viability prior to transplantation, offering significant advantages to the transplant surgeon, and leading to a potential increase in the organ donor pool. MicroRNAs are emerging as important biomarkers in the context of kidney injury and transplantation. Recent data demonstrate increased microRNA‐21 (miR‐21) expression in the kidney following acute kidney injury. This study investigated the potential of miR‐21 detected in HMP to act as a sentinel for early kidney transplant outcomes. MiR‐21 was found to be readily detectable in HMP by RT‐qPCR. Eleven ECD kidneys were maintained on a hypothermic machine perfusion system for a median 627 (range 117–1027) minutes, and evaluation of flow and resistance characteristics suggested stability on the machine from 60 min post‐perfusion. MiR‐21 quantification at 60 min post‐perfusion correlated with eGFR at 6 and 12 months post‐transplantation. These data suggest that miR‐21 expression in HMP may be predictive of early outcomes following kidney transplantation. In the era of ECD kidneys, a reliable measure of organ quality is urgently needed, and this study suggests miR‐21 may be such a marker.     

Associations of Perfusate Biomarkers and Pump Parameters With Delayed Graft Function and Deceased Donor Kidney Allograft Function

Hypothermic machine perfusion (HMP) is increasingly used in deceased donor kidney transplantation, but controversy exists regarding the value of perfusion biomarkers and pump parameters for assessing organ quality. We prospectively determined associations between perfusate biomarkers (neutrophil gelatinase–associated lipocalin [NGAL], kidney injury molecule 1, IL‐18 and liver‐type fatty acid–binding protein [L‐FABP]) and pump parameters (resistance and flow) with outcomes of delayed graft function (DGF) and 6‐mo estimated GFR (eGFR). DGF occurred in 230 of 671 (34%) recipients. Only 1‐h flow was inversely associated with DGF. Higher NGAL or L‐FABP concentrations and increased resistance were inversely associated with 6‐mo eGFR, whereas higher flow was associated with higher adjusted 6‐mo eGFR. Discarded kidneys had consistently higher median resistance and lower median flow than transplanted kidneys, but median perfusate biomarker concentrations were either lower or not significantly different in discarded compared with transplanted kidneys. Notably, most recipients of transplanted kidneys with isolated “undesirable” biomarker levels or HMP parameters experienced acceptable 6‐mo allograft function, suggesting these characteristics should not be used in isolation for discard decisions. Additional studies must confirm the utility of combining HMP measurements with other characteristics to assess kidney quality.     

The Prognostic Value of Renal Resistance During Hypothermic Machine Perfusion of Deceased Donor Kidneys

Vascular renal resistance (RR) during hypothermic machine perfusion (HMP) is frequently used in kidney graft quality assessment. However, the association between RR and outcome has never been prospectively validated. Prospectively collected RR values of 302 machine‐perfused deceased donor kidneys of all types (standard and extended criteria donor kidneys and kidneys donated after cardiac death), transplanted without prior knowledge of these RR values, were studied. In this cohort, we determined the association between RR and delayed graft function (DGF) and 1‐year graft survival. The RR (mmHg/mL/min) at the end of HMP was an independent risk factor for DGF (odds ratio 21.12 [1.03–435.0]; p = 0.048) but the predictive value of RR was low, reflected by a c‐statistic of the receiver operator characteristic curve of 0.58. The RR was also found to be an independent risk factor for 1‐year graft failure (hazard ratio 12.33 [1.11–136.85]; p = 0.004). Determinants of transplant outcome are multifactorial in nature and this study identifies RR as an additional parameter to take into account when evaluating graft quality and estimating the likelihood of successful outcome. However, RR as a stand‐alone quality assessment tool cannot be used to predict outcome with sufficient precision.     

Reconditioning by end‐ischemic hypothermic in‐house machine perfusion: A promising strategy to improve outcome in expanded criteria donors kidney transplantation

This clinical study evaluates end‐ischemic hypothermic machine perfusion (eHMP) in expanded criteria donors (ECD) kidneys. eHMP was initiated upon arrival of the kidney in our center and continued until transplantation. Between 11/2011 and 8/2014 eHMP was performed in 66 ECD kidneys for 369 (98‐912) minutes after 863 (364‐1567) minutes of cold storage (CS). In 49 of 66 cases, the contralateral kidney from the same donor was preserved by static CS only and accepted by another Eurotransplant (ET) center. Five (10.2%) of these kidneys were ultimately judged as “not transplantable” by the accepting center and discarded. After exclusion of early unrelated graft losses, 43 kidney pairs from the same donor were eligible for direct comparison of eHMP vs CS only: primary non‐function and delayed graft function (DGF) were 0% vs 9.3% (P=.04) and 11.6% vs 20.9% (P=.24). There was no statistically significant difference in 1‐year graft survival (eHMP vs CS only: 97.7% vs 88.4%, P=.089). In a multivariate analysis, eHMP was an independent factor for prevention of DGF (OR: 0.28, P=.041). Development of DGF was the strongest risk factor for 1‐year graft failure (Renal resistance: 38.2, P<.001). In summary, eHMP is a promising reconditioning technique to improve the quality and acceptance rate of suboptimal grafts.     

Subnormothermic machine perfusion for preservation of porcine kidneys in a donation after circulatory death model

Machine perfusion for preservation led to compelling success for the outcome of renal transplantation. Further refinements of methods to decrease preservation injury remain an issue of high interest. This study investigates functional and morphological aspects of kidneys preserved by subnormothermic (20 °C) machine perfusion (SNTM) compared with oxygenated hypothermic machine perfusion (HMPox) and cold storage (CS) in a donation after circulatory death (DCD) model. After 30 min of warm ischaemia, porcine kidneys were randomly assigned to preservation for 7 h by CS, HMPox or SNTM. Afterwards, kidneys were reperfused for 2 h with autologous blood in vitro for assessment of function and integrity. Application of SNTM for preservation led to significantly higher blood flow and urine output compared with both other groups. SNTM led to a twofold increased creatinine clearance compared with HMPox and 10‐fold increased creatinine clearance compared with CS. Structural integrity was best preserved by SNTM. In conclusion, this is the first study on SNTM for kidneys from DCD donors. SNTM seems to be a promising preservation method with the potential to improve functional parameters of kidneys during reperfusion.