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 18 065 recipients of deceased‐donor kidney transplants in the Eurotransplant region: 1059 DCD and 17 006 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 560/17 006; 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 5 years after transplantation, graft failure occurred in 14 of 133 recipients (10.5%) with DWIT <10 minutes, 139 of 555 recipients (25.0%) with DWIT between 10 and 19 minutes, and 117 of 371 recipients (31.5%) with DWIT ≥20 minutes. These findings support the expert opinion–based guidelines to limit DWIT.     

Transplanting kidneys from donation after cardiac death donors with acute kidney injury

Donation after cardiac death (DCD) and acute kidney injury (AKI) donors have historically been considered independent risk factors for delayed graft function (DGF), allograft failure, and inferior outcomes. With growing experience, updated analyses have shown good outcomes. There continues to be limited data, however, on outcomes specific to DCD donors who have AKI. Primary outcomes for this study were post–kidney transplant patient and allograft survival comparing two donor groups: DCD AKIN stage 2‐3 and DBD AKIN stage 2‐3. In comparing these groups, there were no short‐ or long‐term differences in patient (hazard ratio [HR] 1.07, 95% confidence interval [CI] 0.54‐1.93, P = .83) or allograft survival (HR 1.47, 95% CI 0.64‐2.97, P = .32). In multivariate models, the DCD/DBD status had no significant impact on the estimated GFR (eGFR) at 1 (P = .38), 2 (P = .60), and 3 years (P = .52). DGF (57.9% vs 67.9%, P = .09), rejection (12.1% vs 13.9%, P = .12), and progression of interstitial fibrosis/tubular atrophy (IFTA) on protocol biopsy (P = .16) were similar between the two groups. With careful selection, good outcomes can be achieved utilizing severe AKI DCD kidneys. Historic concerns regarding primary nonfunction, DGF resulting in interstitial fibrosis and rejection, and inferior outcomes were not observed. Given the ongoing organ shortage, increased effort should be undertaken to further utilize these donors.     

Kidneys from uncontrolled donors after cardiac death: which kidneys do worse?

Kidneys from uncontrolled donors after cardiac death (DCD) expand the donor pool, but are associated with more primary nonfunction (PNF) and delayed graft function (DGF) compared with more conventional donor kidneys. It remains unclear, which factors influence outcome of uncontrolled donation. Therefore, we studied which donor, graft, and recipient characteristics are associated with PNF in a large cohort study. The association between different characteristics and short‐term graft function was analyzed for kidneys procured in the Maastricht region from 1 January 1981 to 1 July 2009. Patients were followed until 7 January 2010. A total of 135 uncontrolled donor kidneys were included in this study. The incidence of PNF and DGF was 22% and 61%, respectively. Increasing donor age is an independent risk factor for graft failure in a univariate analysis (OR 1.035, 95% CI 1.004–1.068, P = 0.028). Donor age remains strongly associated with PNF in a multivariate analysis (OR 1.064, 95% CI 1.013–1.118, P = 0.014). However, the predictive value of donor age alone is poor (AURC 0.640, 95% CI 0.553–0.721). Increasing donor age of uncontrolled DCD donors is a major risk factor for PNF. Other clinically relevant variables were not associated with PNF. Donor age is strongly associated with PNF and remains an important parameter in donor selection.     

Kidney transplant from uncontrolled donation after circulatory death donors maintained by nECMO has long‐term outcomes comparable to standard criteria donation after brain death

Uncontrolled donation after circulatory death (uDCD) increases organ availability for kidney transplant (KT) with short‐term outcomes similar to those obtained from donation after brain death (DBD) donors. However, heterogeneous results in the long term have been reported. We compared 10‐year outcomes between 237 KT recipients from uDCD donors maintained by normothermic extracorporeal membrane oxygenation (nECMO) and 237 patients undergoing KT from standard criteria DBD donors during the same period at our institution. We further analyzed risk factors for death‐censored graft survival in the uDCD group. Delayed graft function (DGF) was more common in the uDCD group (73.4% vs 46.4%; P < .01), although glomerular filtration rates at the end of follow‐up were similar in the 2 groups. uDCD and DBD groups had similar rates for 10‐year death‐censored graft (82.1% vs 80.4%; P = .623) and recipient survival (86.2% vs 87.6%; P = .454). Donor age >50 years was associated with graft loss in the uDCD group (hazard ratio: 1.91; P = .058), whereas the occurrence of DGF showed no significant effect. uDCD KT under nECMO support resulted in similar graft function and long‐term outcomes compared with KT from standard criteria DBD donors. Increased donor age could negatively affect graft survival after uDCD donation.     

Effect of delayed graft function on longer-term outcomes after kidney transplantation from donation after circulatory death donors in the United Kingdom: A national cohort study

Kidneys from donation after circulatory death (DCD) donors are utilized variably worldwide, in part due to high rates of delayed graft function (DGF) and putative associations with adverse longer-term outcomes. We aimed to determine whether the presence of DGF and its duration were associated with poor longer-term outcomes after kidney transplantation from DCD donors. Using the UK transplant registry, we identified 4714 kidney-only transplants from controlled DCD donors to adult recipients between 2006 and 2016; 2832 recipients (60·1%) had immediate graft function and 1882 (39·9%) had DGF. Of the 1847 recipients with DGF duration recorded, 926 (50·1%) had DGF < 7 days, 576 (31·2%) had DGF 7–14 days, and 345 (18·7%) had DGF >14 days. After risk adjustment, the presence of DGF was not associated with inferior long-term graft or patient survivals. However, DGF duration of >14 days was associated with an increased risk of death-censored graft failure (hazard ratio 1·7, p = ·001) and recipient death (hazard ratio 1·8, p < ·001) compared to grafts with immediate function. This study suggests that shorter periods of DGF have no adverse influence on graft or patient survival after DCD donor kidney transplantation and that DGF >14 days is a novel early biomarker for significantly worse longer-term outcomes.     

Predictor parameters of liver viability during porcine normothermic ex situ liver perfusion in a model of liver transplantation with marginal grafts

Normothermic ex situ liver perfusion (NEsLP) offers the opportunity to assess biomarkers of graft function and injury. We investigated NEsLP parameters (biomarkers and markers) for the assessment of liver viability in a porcine transplantation model. Grafts from heart‐beating donors (HBD), and from donors with 30 minutes (donation after cardiac death [DCD]30′), 70 minutes (DCD70′), and 120 minutes (DCD120′) of warm ischemia were studied. The HBD, DCD30′, and DCD70′‐groups had 100% survival. In contrast, 70% developed primary nonfunction (PNF) and died in the DCD120′‐group. Hepatocellular function during NEsLP showed low lactate (≤1.1 mmol/L) in all the groups except the DCD120′‐group (>2 mmol/L) at 4 hours of perfusion (P = .04). The fold‐urea increase was significantly lower in the DCD120′‐group (≤0.4) compared to the other groups (≥0.65) (P = .01). As for cholangiocyte function, bile/perfusate glucose ratio was significantly lower (<0.6) in all the groups except the DCD120′‐group (≥0.9) after 3 hours of perfusion (<0.01). Bile/perfusate Na+ ratio was significantly higher (≥1.2) after 3 hours of perfusion in all the groups except for the DCD120′‐group (≤1) (P < .01). Three hours after transplantation, the DCD120′‐group had a significantly higher international normalized ratio (>5) compared to the rest of the groups (≤1.9) (P = .02). Rocuronium levels were higher at all the time‐points in the animals that developed PNF during NEsLP and after transplantation. This study demonstrates that biomarkers and markers of hepatocellular and cholangiocyte function during NEsLP correlate with the degree of ischemic injury and posttransplant function.     

Duration of delayed graft function and outcomes after kidney transplantation from controlled donation after circulatory death donors: a retrospective study

The impact of the duration of delayed graft function (DGF) on graft survival is poorly characterized in controlled donation after circulatory death (DCD) donor kidney transplantation. A retrospective analysis was performed on 225 DCD donor kidney transplants between 2011 and 2016. When patients with primary nonfunction were excluded (n = 9), 141 recipients (65%) had DGF, with median (IQR) duration of dialysis dependency of 6 (2–11.75) days. Longer duration of dialysis dependency was associated with lower estimated glomerular filtration rate at 1 year, and a higher rate of acute rejection. On Kaplan–Meier analysis, the presence of DGF was associated with lower graft survival (log‐rank test P = 0.034), though duration of DGF was not (P = 0.723). However, multivariable Cox regression analysis found that only acute rejection was independently associated with lower graft survival [HR (95% CI) 4.302 (1.617–11.450); P = 0.003], whereas the presence of DGF and DGF duration were not. In controlled DCD kidney transplantation, DGF duration itself may not be independently associated with graft survival; rather, it may be that acute rejection associated with prolonged DGF is the poor prognostic factor.     

In situ normothermic perfusion of livers in controlled circulatory death donation may prevent ischemic cholangiopathy and improve graft survival

Livers from controlled donation after circulatory death (DCD) donors suffer a higher incidence of nonfunction, poor function, and ischemic cholangiopathy. In situ normothermic regional perfusion (NRP) restores a blood supply to the abdominal organs after death using an extracorporeal circulation for a limited period before organ recovery. We undertook a retrospective analysis to evaluate whether NRP was associated with improved outcomes of livers from DCD donors. NRP was performed on 70 DCD donors from whom 43 livers were transplanted. These were compared with 187 non‐NRP DCD donor livers transplanted at the same two UK centers in the same period. The use of NRP was associated with a reduction in early allograft dysfunction (12% for NRP vs. 32% for non‐NRP livers, P = .0076), 30‐day graft loss (2% NRP livers vs. 12% non‐NRP livers, P = .0559), freedom from ischemic cholangiopathy (0% vs. 27% for non‐NRP livers, P < .0001), and fewer anastomotic strictures (7% vs. 27% non‐NRP, P = .0041). After adjusting for other factors in a multivariable analysis, NRP remained significantly associated with freedom from ischemic cholangiopathy (P < .0001). These data suggest that NRP during organ recovery from DCD donors leads to superior liver outcomes compared to conventional organ recovery.     

Urinary metabolites predict prolonged duration of delayed graft function in DCD kidney transplant recipients

Extending kidney donor criteria, including donation after circulatory death (DCD), has resulted in increased rates of delayed graft function (DGF) and primary nonfunction. Here, we used Nuclear Magnetic Resonance (NMR) spectroscopy to analyze the urinary metabolome of DCD transplant recipients at multiple time points (days 10, 42, 180, and 360 after transplantation). The aim was to identify markers that predict prolonged duration of functional DGF (fDGF). Forty‐seven metabolites were quantified and their levels were evaluated in relation to fDGF. Samples obtained at day 10 had a different profile than samples obtained at the other time points. Furthermore, at day 10 there was a statistically significant increase in eight metabolites and a decrease in six metabolites in the group with fDGF (N = 53) vis‐à‐vis the group without fDGF (N = 22). In those with prolonged fDGF (≥21 days) (N = 17) urine lactate was significantly higher and pyroglutamate lower than in those with limited fDGF (<21 days) (N = 36). In order to further distinguish prolonged fDGF from limited fDGF, the ratios of all metabolites were analyzed. In a logistic regression analysis, the sum of branched‐chain amino acids (BCAAs) over pyroglutamate and lactate over fumarate, predicted prolonged fDGF with an AUC of 0.85. In conclusion, kidney transplant recipients with fDGF can be identified based on their altered urinary metabolome. Furthermore, two ratios of urinary metabolites, lactate/fumarate and BCAAs/pyroglutamate, adequately predict prolonged duration of fDGF.     

Uncontrolled donation after circulatory death: A cohort study of data from a long‐standing deceased‐donor kidney transplantation program

Despite good long‐term outcomes of kidney transplants from controlled donation after circulatory death (DCD) donors, there are few uncontrolled DCD (uDCD) programs. This longitudinal study compares outcomes for all uDCD (N = 774) and all donation after brain death (DBD) (N = 613) kidney transplants performed from 1996 to 2015 at our center. DBD transplants were divided into those from standard‐criteria (SCD) (N = 366) and expanded‐criteria (N = 247) brain‐dead donors (ECD). One‐, 5‐, and 10‐year graft survival rates were 91.7%, 85.7%, and 80.6% for SCD; 86.0%, 75.8%, and 61.4% for ECD; and 85.1%, 78.1%, and 72.2% for uDCD, respectively. Graft survival was worse in recipients of uDCD kidneys than of SCD (P = .004) but better than in transplants from ECD (P = .021). The main cause of graft loss in the uDCD transplants was primary nonfunction. Through logistic regression, donor death due to pulmonary embolism (OR 4.31, 95% CI 1.65‐11.23), extrahospital CPR time ≥75 minutes (OR1.94, 95%CI 1.18‐3.22), and in‐hospital CPR time ≥50 minutes (OR 1.79, 95% CI 1.09‐2.93) emerged as predictive factors of primary nonunction. According to the outcomes of our long‐standing kidney transplantation program, uDCD could help expand the kidney donor pool.     

Mitochondrial membrane potential and delayed graft function following kidney transplantation

Delayed graft function (DGF) complicates 20%‐40% of deceased‐donor kidney transplants and is associated with increased length of stay and subsequent allograft failure. Accurate prediction of DGF risk for a particular allograft could influence organ allocation, patient counseling, and postoperative planning. Mitochondrial dysfunction, a reported surrogate of tissue health in ischemia‐perfusion injury, might also be a surrogate for tissue health after organ transplantation. To understand the potential of mitochondrial membrane potential (MMP) in clinical decision‐making, we analyzed whether lower MMP, a measure of mitochondrial dysfunction, was associated with DGF. In a prospective, single‐center proof‐of‐concept study, we measured pretransplant MMP in 28 deceased donor kidneys and analyzed the association between MMP and DGF. We used hybrid registry‐augmented regression to adjust for donor and recipient characteristics, minimizing overfitting by leveraging Scientific Registry of Transplant Recipients data. The range of MMP levels was 964‐28 333 units. Low‐MMP kidneys (MMP<4000) were more likely from female donors (75% vs 10%, P = .002) and donation after cardiac death donors (75% vs 12%, P = .004). For every 10% decrease in MMP levels, there were 38% higher odds of DGF (adjusted odds ratio = _1.081.38_1.78, P = .01). In summary, MMP might be a promising pretransplant surrogate for tissue health in kidney transplantation and, after further validation, could improve clinical decision‐making through its independent association with DGF.     

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.     

Delayed kidney graft function in simultaneous pancreas‐kidney transplant recipients is associated with early pancreas allograft failure

Delayed graft function (DGF) is a common complication associated with significant untoward effects in kidney‐alone transplantation. The incidence and outcomes following kidney delayed graft function (K‐DGF) among patients undergoing simultaneous pancreas‐kidney (SPK) transplantation are less certain. We analyzed SPK recipients transplanted at our center between January 1994 and December 2017. A total of 632 recipients fulfilled the selection criteria, including 69 (11%) with K‐DGF and 563 without. The incidence of K‐DGF was significantly higher in recipients of organs from older donors and donation after circulatory death (DCD). The presence of K‐DGF was significantly associated with an increased risk of pancreas graft failure during the first 90 days (n = 9, incidence rate [IR] 2.45/100 person‐months), but not with late pancreas failure (n = 32, IR 0.84/100 person‐months), kidney graft failure, or patient death. Although DCD was associated with K‐DGF, it was not associated with either pancreas (hazard ratio [HR] 0.91, 95% CI 0.58‐1.44, P = .69) or kidney (HR 1.09, 95% CI 0.66‐1.82, P = .74) graft failure after adjustment for potential confounders. We found K‐DGF to be a significant risk factor for pancreas graft failure but not kidney graft failure, with the major risk period being early (<90 days) posttransplant, and the major donor risk factor being older donor age.     

Impact of the kidney allocation system on young pediatric recipients

The kidney allocation system (KAS) altered pediatric candidate prioritization. We determined KAS's impact on pediatric kidney recipients by examining delayed graft function (DGF) rates from 2010 to 2016. A propensity score‐matched pediatric recipients pre‐ and post‐KAS. A semiparametric decomposition analysis estimated the contributions of KAS‐related changes in donor characteristics and dialysis time on DGF rate. The unadjusted odds of DGF were 69% higher post‐KAS for young (<10 years at listing) recipients (N = 1153, P = .02) but were not significantly increased for older pediatric (10‐17 years at listing) recipients (N = 2624, P = .48). Post‐KAS, young recipients received significantly fewer pediatric (<18 years) donor kidneys (21% vs 32%, P < .01) and had longer median pretransplant dialysis time (603 vs 435 days, P < .01). After propensity score matching, post‐KAS status increased the odds of DGF in young recipients 71% (OR 1.71, 95% CI 1.01‐2.46). In decomposition analysis, 24% of the higher DGF rate post‐KAS was attributable to donor characteristics and 19% to increased recipient dialysis time. In a confirmatory survival analysis, DGF was associated with a 2.2 times higher risk of graft failure (aHR2.28, 95% CI 1.46‐3.54). In conclusion, KAS may lead to worse graft survival outcomes in children. Allocation changes should be considered.     

Shipping living donor kidneys and transplant recipient outcomes

Kidney paired donation (KPD) is an important tool to facilitate living donor kidney transplantation (LDKT). Concerns remain over prolonged cold ischemia times (CIT) associated with shipping kidneys long distances through KPD. We examined the association between CIT and delayed graft function (DGF), allograft survival, and patient survival for 1267 shipped and 205 nonshipped/internal KPD LDKTs facilitated by the National Kidney Registry in the United States from 2008 to 2015, compared to 4800 unrelated, nonshipped, non‐KPD LDKTs. Shipped KPD recipients had a median CIT of 9.3 hours (range = 0.25‐23.9 hours), compared to 1.0 hour for internal KPD transplants and 0.93 hours for non‐KPD LDKTs. Each hour of CIT was associated with a 5% increased odds of DGF (adjusted odds ratio: 1.05, 95% confidence interval [CI], 1.02‐1.09, P < .01). However, there was not a significant association between CIT and all‐cause graft failure (adjusted hazard ratio [aHR]: 1.01, 95% CI: 0.98‐1.04, P = .4), death‐censored graft failure ( [aHR]: 1.02, 95% CI, 0.98‐1.06, P = .4), or mortality (aHR 1.00, 95% CI, 0.96‐1.04, P > .9). This study of KPD‐facilitated LDKTs found no evidence that long CIT is a concern for reduced graft or patient survival. Studies with longer follow‐up are needed to refine our understanding of the safety of shipping donor kidneys through KPD.     

Impact of donor age on long‐term outcomes after delayed graft function: 10‐year follow‐up

Delayed graft function (DGF) has a negative impact on graft survival in donation after brain death (DBD) but not for donation after cardiac death (DCD) kidneys. However, older donor age is associated with graft loss in DCD transplants. We sought to examine the interaction between donor age and DGF in DBD kidneys. This is a single‐center, retrospective review of 657 consecutive DBD recipients transplanted between 1990 and 2005. We stratified the cohort by decades of donor age and studied the association between DGF and graft failure using Cox models. The risk of graft loss associated with DGF was not significantly increased for donor age below 60 years (adjusted hazard ratio [aHR] 1.12, 1.51, and 0.90, respectively, for age <40, 41–50 and 51–60 years) but significantly increased after 60 years (aHR 2.67; P = 0.019). Analysis of death‐censored graft failure yielded similar results for donor age below 60 years and showed a substantially increased risk with donors above 60 years (aHR 6.98, P = 0.002). This analysis reveals an unexpectedly high impact of older donor age on the association between DGF and renal transplant outcomes. Further research is needed to determine the best use of kidneys from donors above 60 years old, where DGF is expected.     

Targeted donor complement blockade after brain death prevents delayed graft function in a nonhuman primate model of kidney transplantation

Delayed graft function (DGF) in renal transplant is associated with reduced graft survival and increased immunogenicity. The complement‐driven inflammatory response after brain death (BD) and posttransplant reperfusion injury play significant roles in the pathogenesis of DGF. In a nonhuman primate model, we tested complement‐blockade in BD donors to prevent DGF and improve graft survival. BD donors were maintained for 20 hours; kidneys were procured and stored at 4°C for 43‐48 hours prior to implantation into ABO‐compatible, nonsensitized, MHC‐mismatched recipients. Animals were divided into 3 donor‐treatment groups: G1 ‐ vehicle, G2 ‐ rhC1INH+heparin, and G3 ‐ heparin. G2 donors showed significant reduction in classical complement pathway activation and decreased levels of tumor necrosis factor α and monocyte chemoattractant protein 1. DGF was diagnosed in 4/6 (67%) G1 recipients, 3/3 (100%) G3 recipients, and 0/6 (0%) G2 recipients (P = .008). In addition, G2 recipients showed superior renal function, reduced sC5b‐9, and reduced urinary neutrophil gelatinase–associated lipocalin in the first week posttransplant. We observed no differences in incidence or severity of graft rejection between groups. Collectively, the data indicate that donor‐management targeting complement activation prevents the development of DGF. Our results suggest a pivotal role for complement activation in BD‐induced renal injury and postulate complement blockade as a promising strategy for the prevention of DGF after transplantation.     

Impact of machine perfusion after long static cold storage on delayed graft function incidence and duration and time to hospital discharge

Delayed graft function (DGF) is very high in our center (70%‐80%), and we usually receive a kidney for transplant after more than 22 hours of static cold ischemia time (CIT). Also, there is an inadequate care of the donors, contributing to a high rate of DGF. We decided to test whether machine perfusion (MP) after a CIT improved the outcome of our transplant patients. We analyzed the incidence of DGF, its duration, and the length of hospital stay (LOS) in patients who received a kidney preserved with MP after a CIT (hybrid perfusion—HP). We included 54 deceased donors kidneys preserved with HP transplanted from Feb/13 to Jul/14, and compared them to 101 kidney transplants preserved by static cold storage (CS) from Nov/08 to May/12. The median pumping time was 11 hours. DGF incidence was 61.1% vs 79.2% (P = .02), median DGF duration was 5 vs 11 days (P < .001), and median LOS was 13 vs 18 days (P < .011), for the HP compared to CS group. The observed reduction of DGF with machine perfusion did not occur in donors over 50 years old. In the multivariate analysis, risk factors for DGF, adjusted for CIT, were donor age (OR, 1.04; P = .005) and the absence of use of MP (OR, 1.54; P = .051). In conclusion, the use of HP contributed to faster recovery of renal function and to a shorter length of hospital stay.     

Negative impact of prolonged cold storage time before machine perfusion preservation in donation after circulatory death kidney transplantation

Kidney grafts are often preserved initially in static cold storage (CS) and subsequently on hypothermic machine perfusion (MP). However, the impact of CS/MP time on transplant outcome remains unclear. We evaluated the effect of prolonged CS/MP time in a single‐center retrospective cohort of 59 donation after circulatory death (DCD) and 177 matched donation after brain death (DBD) kidney‐alone transplant recipients. With mean overall CS/MP times of 6.0 h/30.0 h, overall incidence of delayed graft function (DGF) was higher in DCD transplants (30.5%) than DBD transplants (7.3%, P < 0.0001). In logistic regression, DCD recipient (P < 0.0001), longer CS time (P = 0.0002), male recipient (P = 0.02), and longer MP time (P = 0.08) were associated with higher DGF incidence. In evaluating the joint effects of donor type (DBD vs. DCD), CS time (<6 vs. ≥6 h), and MP time (<36 vs. ≥36 h) on DGF incidence, one clearly sees an unfavorable effect of MP time ≥36 h (P = 0.003) across each donor type and CS time stratum, whereas the unfavorable effect of CS time ≥6 h (P = 0.01) is primarily seen among DCD recipients. Prolonged cold ischemia time had no unfavorable effect on renal function or graft survival at 12mo post‐transplant. Long CS/MP time detrimentally affects early DCD/DBD kidney transplant outcome when grafts were mainly preserved by MP; prolonged CS time before MP has a particularly negative impact in DCD kidney transplantation.     

Kidney transplantation from donation after cardiac death donors: lack of impact of delayed graft function on post‐transplant outcomes

Singh RP, Farney AC, Rogers J, Zuckerman J, Reeves‐Daniel A, Hartmann E, Iskandar S, Adams P, Stratta RJ. Kidney transplantation from donation after cardiac death donors: lack of impact of delayed graft function on post‐transplant outcomes.
Clin Transplant 2011: 25: 255–264. © 2010 John Wiley & Sons A/S. Abstract: Introduction: Delayed graft function (DGF) is more common in recipients of kidney transplants from donation after cardiac death (DCD) donors compared to donation after brain death (DBD) donors. Methods: Single‐center retrospective study to evaluate the impact of DGF on controlled (Maastricht category III) DCD donor kidney transplant outcomes. Results: From 10/01 to 6/08, 578 adult deceased donor kidney transplants were performed including 70 (12%) from DCD and 508 (88%) from DBD donors. Mean follow‐up was 36 months. DCD donor kidney transplants had significantly greater rates of DGF (57% DCD vs. 21% DBD, p < 0.0001)) and acute rejection (29% DCD vs. 16% DBD, p = 0.018) compared to DBD donor kidney transplants, but patient and graft survival rates were similar. DBD donor kidney transplants with DGF (n = 109) had significantly greater rates of death‐censored graft loss (12.5% DCD vs. 31% DBD), primary non‐function (0 DCD vs. 10% DBD) and higher 2 year mean serum creatinine levels (1.4 DCD vs. 2.7 mg/dL DBD) compared to DCD donor kidney transplants with DGF (n = 40, all p < 0.04). On univariate analysis, the presence of acute rejection and older donor age were the only significant risk factors for death‐censored graft loss in DCD donor kidney transplants, whereas DGF was not a risk factor. Conclusion: Despite higher rates of DGF and acute rejection in DCD donor kidney transplants, subsequent outcomes in DCD donor kidney transplants with DGF are better than in DBD donor kidney transplants experiencing DGF, and similar to outcomes in DCD donor kidney transplants without DGF.