DCD Kidneys Research Articles

Normothermic Ex Vivo Perfusion Before Transplantation of the Kidney (NEXT-Kidney): A Single-center, Nonrandomized Feasibility Study.

There is conflicting evidence regarding the efficacy of normothermic machine perfusion (NMP) in suboptimal deceased donor kidneys. We aimed to assess the feasibility and short-term efficacy of brief preimplantation NMP in circulatory death (DCD) kidneys. In this nonrandomized, single-center, prospective clinical trial, DCD kidneys underwent 1 to 3 h of NMP before implantation, aiming to achieve short ischemic times off NMP. The primary outcomes included feasibility and safety. Secondary outcomes included efficacy outcomes (delayed graft function and estimated glomerular filtration rate (eGFR) at 1, 6, and 12 mo), which were compared with the contralateral kidney that did not receive NMP. Eighteen DCD kidneys underwent NMP between 2020 and 2022, with at least 1 h completed in 16 (88.9%) of these kidneys (median 1 h); one kidney was removed after 5 min because of cannula failure and another at 54 min because of a sudden drop in blood flows. There was no episode of graft loss on the machine or postoperative vascular thromboses. All 18 kidneys were transplanted, with no cases of PNF or graft loss at 12 mo. Seventeen of the contralateral CS kidneys were transplanted. Compared with the contralateral kidneys, a lower incidence of delayed graft function (23.5% versus 64.7%; P = 0.046) was observed. There were no differences in the eGFR slopes between the two groups over time (P = 0.254). NMP is safe, feasible and efficacious in the Australian setting, with this relatively small cohort demonstrating good early outcomes compared to CS alone in our study of DCD kidneys.

Establishing targets for goal-directed anesthesia in renal transplantation: A cohort analysis of high-saliency surgical time courses

Delayed graft function (DGF) increases morbidity and mortality in kidney transplant recipients. Operative parameters, including hemodynamic manipulation through vasopressors and fluids, can impact perfusion to the newly transplanted kidney and influence DGF incidence. We analyzed intraoperative time-series data in 5-minute intervals from kidney transplant recipient operations (N = 545) in conjunction with pretransplant characteristics and postsurgical outcomes, including DGF incidence, 60-day creatinine, and graft survival. Of the operations, 127 DGF events were captured in our cohort from a single academic transplant center (57/278 donations after brainstem death [DBDs], 65/150 donations after circulatory/cardiac death [DCDs], 5/117 live donations). In multiple regression, postanastomosis hypotension defined as mean arterial pressure (MAP) <75 mmHg was a risk factor for DGF independent of conventional predictors of DGF in DCD and DBD kidneys. DCD recipients with DGF had lower average postanastomosis MAP (DGF: 80.1 ± 8.1 mmHg vs no DGF: 76.4 ± 6.7 mmHg, P = .004). Interaction analysis demonstrated above-average doses of vasopressors and crystalloids were associated with improved outcomes when used at MAPs ≤75 mmHg, but they were associated with increased DGF at MAPs >75 mmHg, suggesting that the incidence of DGF can be highly influenced by intraoperative hemodynamic controls. This analysis of surgical time courses has identified potential new strategies for goal-directed anesthesia in renal transplantation.

210.3: Use of mechanical versus manual chest compressions in the recovery of uncontrolled DCD kidneys.

210.3: Use of mechanical versus manual chest compressions in the recovery of uncontrolled DCD kidneys.

WTP2.7 Short and Long term Kidney Transplantation outcomes in Severely Obese Recipients. A UK NHSBT Transplant Registry Big Data Analysis over the last 20 years. An Epidemiology in Transplant Study Group (ETrSG) Initiative

Abstract Purpose Outcomes of renal-transplant-recipients with Class 3 obesity (severely obese) is extremely limited. An outcome-analysis of severely- obese transplant recipients reported to UK-NHSBT-Transplant-Registry was performed. Methods We harmonized the NHSBT-UK-Data to shortlist the renal-transplants performed on Class 3-obese recipients in the UK from 2000-2019. The demographics-report and survival-analysis at 1,3 and 5 years post-transplant were data-mined. Cox-Regression was done to identify predictors of survival. Results N=163 recipients with Class-3 obesity underwent renal-transplant since year 2000 (N=60 DBD, N= 48 DCD &amp; N=55 Living Donor Kidney). The median-recipient-age was 47 years - DBD, 51 years DCD, and 43 years LRD transplants. The odds of females getting renal-transplants were OR 2.44(1.14- 5.19) p=0.01. Median-eGFR at 3 months was 40, 38, and 46.5 mL/min/1.73m2 for DBD, DCD, and LRD recipients, Median-eGFR at 12 months was 42, 46.5, and 51.5 mL/min/1.73m2 for DBD, DCD, and LRD recipients, respectively. The median-KDRI of transplanted kidneys was 1-07 and 1,08 for DBD &amp; DCD kidneys, respectively. The commonest cause of graft-failure was acute-rejection within the first 12-months of transplant. The technical failure-rate was 1.8%. DCD-Grafts were more likely to suffer rejection (OR 2.25(1.13-3.89) p=0.002. The Graft-survival for DBD-kidneys was 97%, 92% and 89% at 1,3 &amp; 5 years, The Graft-survival for DCD-kidneys was 89%, 86%, and 76% at 1,3 &amp; 5 years, Graft-survival for LRD-kidneys was 98%, 95% and 86% at 1,3 &amp; 5 years. (Log-Rank- 0.48). Conclusions Renal-Transplantation for severely-obese patients can be safely done with acceptable survival outcomes. Living donor kidneys have better results, but there is no statistical difference in graft-outcomes from DCD versus DBD-Kidneys.

O049 Interleukin-16 in flush effluent fluid as a biomarker for kidney viability prior to transplantation

Abstract Background Kidney transplantation is limited by the number of transplantable organs. Biomarkers that can predict organ viability will reduce the number of organs currently discarded (13% UK, 2021-22, NHSBT). The kidney microcirculation can be flushed, prior to transplantation, with preservation solution as part of the back-table preparation. The effluent fluid is usually discarded, but we propose this as a source of potential biomarkers. Interleukin-16 (IL-16) is a pro-inflammatory cytokine previously shown to predict viability in liver grafts. Here we examine IL-16 in the context of kidney viability. Methods IL-16 concentration was measured, in the flush effluent, using an electrochemiluminescent multiplex assay. The total protein content of each sample was concurrently measured to normalise the concentration. IL-16 concentrations were then compared to donor characteristics and early transplant outcomes. Results Samples were collected from 30 transplanted kidneys (10 DCD, 10 DBD, 10 live donor) and 5 declined kidneys (4 DCD, 1 DBD). IL-16 concentration was significantly higher in DCD kidneys (mean 81.8+/-38 (SD)) compared to live donor kidneys (17.7+/-18 pg/ml) (p=0.0001). CIT did not affect IL-16 concentration (β=-0.014, p=0.4), nor was IL-16 able to predict delayed graft function. However, IL-16 was significantly higher in kidneys declined for transplantation (transplanted: 54.7+/-30 vs non-transplanted: 98+/-43, p=0.03). Conclusion Flush effluent is a rich source of potential biomarkers. IL-16 concentration in flush effluent fluid correlates with organ quality. With real-time assessment, it will be possible to identify kidneys currently discarded; that are either transplantable directly or would benefit from advanced therapy prior to transplantation.

Intercontinental Deceased-donor Kidney Transplantation in Dutch Antilleans: Favorable Outcomes Despite Prolonged Ischemia.

Intercontinental Deceased-donor Kidney Transplantation in Dutch Antilleans: Favorable Outcomes Despite Prolonged Ischemia.

Uncontrolled donation after cardiac death kidney transplantation: Opportunity to expand the donor pool?

BackgroundCompared to controlled donation after cardiac death (cDCD), uncontrolled DCD (uDCD) kidney transplantation remains an underutilized resource in the United States. However, it is unclear whether long-term allograft outcomes following uDCD are inferior to that of cDCD kidney transplantation. MethodsFrom January 1995 to January 2018, the OPTN/UNOS database was queried to discover all reported cases of uDCD and cDCD kidney transplantation. Primary non-function, delayed graft function, ten-year graft and patient survival were compared among uDCD and cDCD patients. ResultsRates of primary non-function (4.0% [uDCD] vs. 1.8% [cDCD], P < 0.001) and delayed graft function (51.1% [uDCD] vs. 41.7% [cDCD], P < 0.001) were higher following uDCD transplant. However, ten-year graft survival (47.5% [uDCD] vs. 48.4% [cDCD], P = 0.21) and patient survival were similar to cDCD transplantation (59.4% [uDCD] vs. 59.2% [cDCD], P = 0.32). ConclusionAlthough initial allograft outcomes are inferior following uDCD, long-term durability of uDCD kidney allografts is on par to cDCD transplantation. Kidney allografts derived by uDCD may be a viable and durable option to increase the donor pool.

Contrast-enhanced CT texture analysis for the prediction of delayed graft function following kidney transplantation from cadaveric donors.

Delayed graft function (DGF) is a common complication after transplantation of deceased donor kidneys. The aim of this study was to investigate the feasibility of using computed tomography texture analysis (CT-TA) of the donor kidney to predict delayed graft function (DGF) following kidney transplantation from cadaveric donors. We made a retrospective review of all consecutive DBD and DCD kidney donors admitted to our institution and their corresponding KTRs between December 2014 and January 2019. We extracted 15 image features from unenhanced CT and contrast-enhanced CT corresponding to first order and second order Haralick textural features. Predictors of DGF were evaluated by univariable and multivariable analysis. Receiver operating characteristic (ROC) analysis was performed and the area under the ROC curve (AUC) to predict DGF was calculated for the predictors. A total of 115 patients were included in the study. DGF occurred in 15 patients (13%). Recipient body mass index (BMI) (P=0.003) and Skewness (P=0.05) represented independent predictors in the multivariate model. The combination of both clinical and textural features in a bivariate model reached a ROC-AUC of 0.79 (95% CI: 0.64-0.94) in predicting the probability of DGF. Results from this preliminary study suggest that CT texture analysis might be a promising quantitative imaging tool to help physician predict DFG after kidney transplantation from cadaveric donors. 4/5.

Presence of CD163+ macrophages in DCD kidneys with high DGF reduces the risk for acute cellular rejection in 6 months after kidney transplantation

Acute cellular rejection (ACR) occurs in 10% of renal allograft recipients and is characterized by leukocyte infiltration as observed in needle biopsies. ACR onset is subject to several risk factors, including delayed graft function (DGF). As the impact of DGF on the etiology of ACR remains unclear, this study analyzed the association between presence of leukocyte subsets and ACR onset, in DCD kidney biopsies with extensive DGF following transplantation. Immunohistochemical analysis of protocol biopsies taken 10 days after kidney transplantation revealed that patients with high levels of renal CD163+ macrophages have a decreased risk (OR = 0.021, P = 0.008) for ACR in the first 6 months after transplantation. In pre-transplant biopsies of a comparable DCD cohort, with >80% DGF, presence of donor CD163+ macrophages showed no effect on ACR risk. Therefore, leukocyte infiltrate present during the inflammatory response at the time of DGF may contain anti-inflammatory macrophages that exert a protective effect against ACR development.

316.3: Influence of CIT-Induced DGF on Transplant Outcomes Among DCD Kidneys

316.3: Influence of CIT-Induced DGF on Transplant Outcomes Among DCD Kidneys

404.8: The Role and Mechanism of IFN-γ-Uc-MSCs-PEG2 Regulating MDSC Hypermethylation and Inducing Immune Tolerance in DCD Kidney Transplantation

404.8: The Role and Mechanism of IFN-γ-Uc-MSCs-PEG2 Regulating MDSC Hypermethylation and Inducing Immune Tolerance in DCD Kidney Transplantation

Pancreas transplantation from donors after cardiac death – The US experience

IntroductionSince the beginning of pancreas transplantation, the rate of donation after cardiac (or circulatory) death (DCD) accounts for only 3% of all transplants in the US. This is the result of perceived higher complication rates and overall worse outcome with DCD donors. Such misconceptions and an increased demand for deceased donor (DD) organs warrant a systematic review of the use of DCD compared with donation after brain death (DBD) pancreata to objectively assess DCD outcome after pancreas transplantation in the US. MethodsAll 22,160 DD pancreas transplants performed in diabetic patients between 1/1/2001 and 12/31/2020 were included in this analysis. To assess changes in outcomes, patient and graft survival was computed using the Kaplan-Meier method in 5-year intervals. Comprehensive univariate and multivariable comparisons of posttransplant complications and patient and pancreas and kidney graft survival between DCD and DBD pancreas transplants were performed to assess the donor impact. ResultsIn the US over the past 20 years most DCD donors were used for simultaneous pancreas and kidney (SPK) transplants and less often for solitary pancreas transplants. DCD transplants never accounted for more than 4% per year of all pancreas transplants. A comparison of the pancreas donor risk index (pDRI) between DCD and DBD pancreata showed that the only distinguishing factor was DCD donation. SPK patient, pancreas, and kidney graft survival for DCD donors did not change significantly over time. One- and 3 -year DCD patient survival reached 96% and 93%, pancreas graft survival 90% and 84%, and kidney graft survival 96% and 91%, respectively. For the last decade, no differences in patient and graft survival between DCD and DBD donors were detected (P > 0.67). The relative risk for the use of a DCD donor was not increased (P > 0.6). Influential risk factors were older donor and recipient age as well as longer preservation times. Larger transplant center accepted DCD donors more frequently and showed better outcome. While the rate of early pancreas complications was the same for DCD vs. DBD transplants, delayed kidney graft function was significantly higher in DCD kidneys secondary to more long-distance shipping across the country. The multivariable analysis showed a 4-times higher rate in delayed graft function. Longer cold preservation time and older donor age further increased the risk of graft failure. The use of machine perfusion of the kidney graft reduced the relative risk of delayed graft function by 50%. SummaryThe use of DCD donor organs in pancreas transplantation is not associated with higher failure or complication rates in the US. A pancreas offer from a DCD donor should not be the sole reason to decline the organ for transplantation. Careful selection of specific donor and recipient factors, as well as advanced preservation techniques are essential for good outcome.

403 Comparison of Clinical Outcomes for Belatacept Versus Calcineurin Inhibitor Among DCD and/or High KDPI Kidney Transplant Recipients

403 Comparison of Clinical Outcomes for Belatacept Versus Calcineurin Inhibitor Among DCD and/or High KDPI Kidney Transplant Recipients

Use of DCD organs: Expanding the donor pool to increase pediatric transplantation.

The number of children being listed for transplant continues to be greater than the number of available organs. In fact, over the past decade, rates of liver and kidney transplants in pediatric transplantation are essentially unchanged (Am J Transplant. 2020;20:193 and Am J Transplant. 2020;20:20). The use of DCD donors offers a potential solution to organ scarcity; however, the use of DCD organs in pediatric transplantation remains a rare event. Pediatric transplants done using carefully chosen DCD donor organs have shown to have outcomes similar to those seen with the use of donation after brain death (DBD) donors. Herein, we review the literature to examine the utilization of DCD livers and kidneys, outcomes of these allografts, and assess if DCD organs are a viable method to increase organ availability in pediatric transplantation.

Long-term outcomes of transplant kidneys donated after circulatory death.

Donation after circulatory death (DCD) represents up to 40% of used kidney grafts. While studies have shown similar outcomes compared with donation after brain death (DBD) in the short term and mid-term, no data on long-term outcomes exist. We retrospectively analysed patients transplanted at our institution between January 1985 and March 2000. All DCD recipients were matched one-to-one with patients transplanted with DBD grafts during this period according to sex, age and year of transplantation and followed up until December 2020. During this period, 1133 kidney transplantations were performed, of which 122 were with a DCD graft. The median graft survival after 35 years of follow-up was 23 years [277 months {95% confidence interval (CI) 182-372}] in DBD recipients and 24.5 years [289 months (95% CI 245-333)] in DCD recipients (P = 0.65; hazard ratio 0.91). Delayed graft function occurred in 47 patients in the DCD group compared with 23 in the DBD group (P < 0.001), albeit without a significant long-term outcome difference in graft or patient survival. We could not show any difference in graft function in terms of creatinine levels (133 versus 119 µmol/L), proteinuria (370 versus 240 mg/24 h) and glomerular filtration rate slope (-0.6 versus -0.3 mL/min/year) between the two groups for graft survival >20 years. This is the first study to show similar graft survival and function in DCD kidneys compared with DBD kidneys after 35 years of follow-up. DCD grafts are a valuable resource and can be utilized in the same way as DBD grafts.

A novel genomic model for predicting the likelihood of delayed graft function in DCD kidney transplantation.

BackgroundThe high incidence of delayed graft function (DGF) following kidney transplantation with donation after cardiac death allografts (DCD-KT) poses great challenges to transplant clinicians. This study aimed to explore the DGF-related biomarkers and establish a genomic model for DGF prediction specific to DCD KT.MethodsBy data mining a public dataset (GSE43974), the key DGF-related genes in DCD kidney biopsies taken after short-time reperfusion (45–60 min) were identified by differential expression analysis and a LASSO-penalized logistic regression model. Their coefficients for modeling were calculated by multivariate logistic regression. Receiver operating characteristic curves and a nomogram were generated to evaluate its predictive ability for DGF occurrence. Gene set enrichment analysis (GSEA) was performed to explore biological pathways underlying DGF in DCD KT.ResultsFive key DGF-related genes (CHST3, GOLPH3, ZBED5, AKR1C4, and ERRFI1) were first identified, all of which displayed good discrimination for DGF occurrence after DCD KT (all P<0.05). A five-mRNA-based risk score was further established and showed excellent predictive ability (AUC =0.9708, P<0.0001), which was obviously higher than that of the five genes alone. Eight DGF-related biological pathways in DCD kidneys, such as “arachidonic acid metabolism”, “lysosome”, “proximal tubule bicarbonate reclamation”, “glutathione metabolism”, were identified by GSEA (all P<0.05). Moreover, a convenient and visual nomogram based on the genomic risk score was also constructed and displayed high accuracy for DGF prediction specific to DCD KT.ConclusionsThe novel genomic model may effectively predict the likelihood of DGF immediately after DCD KT or even prior to transplantation in the context of normothermic machine perfusion in the future.

Induction with ATG in DCD kidney transplantation; efficacy and relation of dose and cell markers on delayed graft function and renal function

AimWe aimed to analyse the efficacy of the Thymoglobulin dose used for induction in controlled DCD kidneys, and its initial impact on blood cell and CD3 count, as predictors of efficacy. Methods140 DCD patients who received ATG induction, were analysed. Intended dose was 1.25 mg/kg/day over 5 days, rounded to nearest 25 mg and not exceeding 125 mg/dose. Outcomes included the total dose in relation with rejection, DGF, graft survival, eGFR. The cell count response to ATG was assessed as predictors of outcome. ResultsGraft survival, was 96.2%, 92.4%, 85% at 1, 3 and 5 years. Rejection was 7% at 1 year and associated with eGFR at 3 (p = 0.003) and 5 years. ATG dose was not predictive of rejection but was associated with the day5 leucocyte and lymphocyte count (p < 0.001) and negatively with DGF (p = 0.05). In 31 patients day3 CD3 count was available and it was associated with rejection (p = 0.002), less DGF (p = 0.09), and 3 years eGFR (p = 0.01). ConclusionThymoglobulin provides excellent results in DCD kidneys that do not significantly differ with small dose variations. In higher doses it reduces DGF. Lymphocytes and CD3 count, may be useful surrogate markers of efficacy and outcome.

Impact of warm ischemia time on outcomes for kidneys donated after cardiac death Post-KAS.

Prolonged warm (WIT) and cold (CIT) ischemia times are often important considerations in the discard of DCD kidneys, but their impact on post-transplant outcomes in the post-KAS era is unclear. We examined the association of ischemia time on delayed graft function (DGF) and death-censored graft failure for DCD kidneys. The 2018 SRTR SAF was utilized to identify post-KAS DCD kidney transplants occurring from 2015 to 2018. Relative risk and Cox regression were used to calculate risk of delayed graft function and hazard of death-censored graft failure, respectively. We identified 4,680 kidneys from DCD donors transplanted from 2015 to 2018 with recorded WIT and CIT times. Median WIT was 21.0minutes (IQR 14.0-28.0), and CIT was 18.5hours (IQR 13.9-23.5). The overall incidence of DGF was 42.7%. In a univariable relative risk regression model, extended CIT (24-30hours:RR 1.37, 95% CI 1.15-1.77; >30hours:RR 1.47, 95% CI 1.22-1.77) and WIT (20-40minutes:RR 1.10, 95% CI 1.03-1.17) were associated with increased risk of DGF. When included in a multivariable model, neither prolonged CIT nor WIT were significantly associated with death-censored graft failure. Prolonged WIT and CIT are associated with increased DGF but not death-censored graft failure in recipients of DCD kidney transplants in the post-KAS era. Extended ischemia alone should not be used as a basis for discard or non-utilization of these organs.

Kidney transplant outcomes from donation after circulatory death donors of advanced age.

Continued comparison of kidney transplant outcomes between older DCD and donation after brain death (DBD) donors is needed to safely expand the deceased donor pool. We performed a retrospective cohort study using the UNOS/OPTN transplant registry from donors >50years old between 1994 and 2016. Donor age was stratified into 4 groups: 50-54, 55-59, 60-64, and >65years old. Rates of delayed graft function (DGF) and primary non-function (PNF) were compared. Multivariable Cox regression models were constructed to identify factors associated with time to graft failure. The DCD donors within each age group had fewer comorbidities than the DBD donors. Graft survival for DCD kidneys was equivalent or superior to DBD kidneys in all donor age groups. DGF rates were significantly greater for DCD kidneys in all age groups. PNF rates across all groups were similar. In multivariable analysis, DCD status was not independently associated with time to all-cause graft failure in the 50-54 donor age group (HR=1.02, 95% CI=0.93-1.13), 55-59 donor age group (HR=1.07, 95% CI=0.96-1.19), or 60-64 donor age group (HR=1.135, 95% CI=0.97-1.32). Kidneys from carefully selected older DCD donors, particularly ages 50-64, are a potential means to safely expand the deceased donor pool.

Comparison Between Kidney Transplantation After Circulatory Death and After Brain Death: A Monocentric Retrospective Study After 1 Year of Follow-up

BackgroundDonation after circulatory death (DCD) is a solid resource to widen the kidney donor pool. Italian activity has grown in the last years with encouraging results. Our center has been active in DCD kidney transplantation (KTX) since November 2017, providing 22.5% of Italian DCD donations in 2018. We present a single-center retrospective analysis after a 1-year follow-up comparing DCD and donation after brain death (DBD) KTX outcomes. MethodsDCD (controlled only) and DBD KTX performed in our center from November 2017 to December 2018 were considered. All DCDs underwent in situ normothermic perfusion with extracorporeal membrane oxygenation, ex situ hypothermic oxygenated perfusion, and renal biopsy prior to allocation.We considered features of donors and recipients, immunosuppressive regimen, delayed graft function (DGF), primary nonfunction (PNF), graft and patient survival (Kaplan-Meier), creatinine, and estimated glomerular filtration rate at 1 year. Mean comparison with a Student t test and with χ2 test for frequencies were elaborated. ResultsTwenty-eight DBD, 18 double (64.3%) and 10 single (35.7%), were performed; 7 DCD, 3 double (42.8%) and 4 single (57.2%), were performed. By comparing single and double KTX, no statistically significant difference was found. We recorded 7 DGFs (25%) in DBD and 1 (14.3%) in the DCD group (P > .99) and no PNF. No graft was lost during the first year. One-year estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration) was, respectively, 62.7 ± 25.3 and 54.71 ± 14.66 mL/min (P = .25). DBD patient survival rate was 92.8%, DCD was 100%, and Kaplan-Meier was not statistically significant (P = .72). ConclusionsControlled DCD is a valid resource for KTX, with similar outcomes to DBD. A multidisciplinary donor evaluation, combining clinical, perfusion, and histologic data in the allocation process, allows excellent results.