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.     

How important is the duration of the brain death period for the outcome in kidney transplantation?

In kidney transplantation, graft survival using grafts from donation after brain death (DBD) donors is inferior to results after living donation. However, little is known about the effect of the duration of brain death (BDdur) on outcome after transplantation. This is a retrospective Organ Procurement and Transplant Network analysis using kidney donor and recipient data from 1994 to 2006. BDdur was calculated as the period between brain death declaration and aortic cross clamp. Effects of BDdur on delayed graft function (DGF), acute rejection and graft failure were calculated using binary logistic regression and Cox regression models. Median BDdur was 23.8 h. Longer BDdur decreased the risk for DGF and 1‐ and 3‐year graft failure slightly, but not for acute rejection. In multivariate analysis, donor age and acute rejection were confounders. However, in a multivariate subgroup analysis of donors aged ≤55 years BDdur independently predicted DGF; each hour of BDdur decreasing the risk of DGF with 0.4% (P = 0.008). Longer BDdur is not detrimental and in fact slightly beneficial in DBD donors ≤55 years of age, reducing the chance of DGF in the recipient. This finding may have an impact on organ retrieval procedures, as no rush but rather an improved donor management prior to retrieval will benefit donor kidney viability.     

Local Expansion of Donation After Circulatory Death Kidney Transplant Activity Improves Waitlisted Outcomes and Addresses Inequities of Access to Transplantation

In the United Kingdom, donation after circulatory death (DCD) kidney transplant activity has increased rapidly, but marked regional variation persists. We report how increased DCD kidney transplant activity influenced waitlisted outcomes for a single center. Between 2002–2003 and 2011–2012, 430 (54%) DCD and 361 (46%) donation after brain death (DBD) kidney‐only transplants were performed at the Cambridge Transplant Centre, with a higher proportion of DCD donors fulfilling expanded criteria status (41% DCD vs. 32% DBD; p = 0.01). Compared with U.K. outcomes, for which the proportion of DCD:DBD kidney transplants performed is lower (25%; p < 0.0001), listed patients at our center waited less time for transplantation (645 vs. 1045 days; p < 0.0001), and our center had higher transplantation rates and lower numbers of waiting list deaths. This was most apparent for older patients (aged >65 years; waiting time 730 vs. 1357 days nationally; p < 0.001), who received predominantly DCD kidneys from older donors (mean donor age 64 years), whereas younger recipients received equal proportions of living donor, DBD and DCD kidney transplants. Death‐censored kidney graft survival was nevertheless comparable for younger and older recipients, although transplantation conferred a survival benefit from listing for only younger recipients. Local expansion in DCD kidney transplant activity improves survival outcomes for younger patients and addresses inequity of access to transplantation for older recipients.     

Short- and Long-Term Outcomes with the Use of Kidneys and Livers Donated after Cardiac Death

The shortage of deceased donor kidneys and livers for transplantation has prompted the use of organs from donors deceased after cardiac death (DCD). We used the UNOS database to examine patient and graft survival following transplantation of DCD organs compared to those following grafts from donors deceased after brain death (DBD; for livers, grafts from donors < 60 years old were labeled '< 60 yrs'). Of 44035 deceased donor kidney transplant recipients, 1177 (3%) received a DCD kidney. There was no difference in patient or graft survival at 5 years (DCD vs. DBD: 81.3% vs. 80.8% and 66.9% vs. 66.5%; p = 0.70 and p = 0.52 respectively). Of 24688-deceased donor liver transplant recipients, 345 (1.4%) were from DCD donors and 20289 (82%) were from '< 60 yrs' DBD donors. Three-year patient and graft survival were inferior in the DCD group (DCD vs. '< 60 yrs' DBD: 77% vs. 80% and 65% vs. 75%; p = 0.016 and p < 0.0001 respectively) but were comparable to current alternatives, '>/= 60 yrs' DBD livers (donor age >/= 60) and split livers. DCD livers are a reasonable option when death is imminent. Our study demonstrates good outcomes using DCD kidneys and livers and encourages their use.     

Expanding the Donor Kidney Pool: Utility of Renal Allografts Procured in a Setting of Uncontrolled Cardiac Death

The chronic shortage of deceased kidney donors has led to increased utilization of donation after cardiac death (DCD) kidneys, the majority of which are procured in a controlled setting. The objective of this study is to evaluate transplantation outcomes from uncontrolled DCD (uDCD) donors and evaluate their utility as a source of donor kidneys. From January 1995 to December 2004, 75,865 kidney-alone transplants from donation after brain death (DBD) donors and 2136 transplants from DCD donors were reported to the United Network for Organ Sharing. Among the DCD transplants, 1814 were from controlled and 216 from uncontrolled DCD donors. The log-rank test was used to compare survival curves. The incidence of delayed graft function in controlled DCD (cDCD) was 42% and in uDCD kidneys was 51%, compared to only 24% in kidneys from DBD donors (p < 0.001). The overall graft and patient survival of DCD donors was similar to that of DBD donor kidneys (p = 0.66; p = 0.88). Despite longer donor warm and cold ischemic times, overall graft and patient survival of uDCD donors was comparable to that of cDCD donors (p = 0.65, p = 0.99). Concerted efforts should be focused on procurement of uDCD donors, which can provide another source of quality deceased donor kidneys.     

Predictors and outcomes of delayed graft function after living‐donor kidney transplantation

Delayed graft function (DGF) following deceased donor kidney transplantation is associated with inferior outcomes. Delayed graft function following living‐donor kidney transplantation is less common, but its impact on graft survival unknown. We therefore sought to determine risk factors for DGF following living‐donor kidney transplantation and DGF's effect on living‐donor kidney graft survival. We analyzed living‐donor kidney transplants performed between 2000 and 2014 in the UNOS dataset. A total of 64 024 living‐donor kidney transplant recipients were identified, 3.6% developed DGF. Cold ischemic time, human leukocyte antigen mismatch, donor age, panel reactive antibody, recipient diabetes, donor and recipient body mass index, recipient race and gender, right nephrectomy, open nephrectomy, dialysis status, ABO incompatibility, and previous transplants were independent predictors of DGF in living‐donor kidney transplants. Five‐year graft survival among living‐donor kidney transplant recipients with DGF was significantly lower compared with graft survival in those without DGF (65% and 85%, respectively, P < 0.001). DGF more than doubled the risk of subsequent graft failure (hazard ratio = 2.3, 95% confidence interval: 2.1–2.6; P < 0.001). DGF after living‐donor kidney transplantation is associated with inferior allograft outcomes. Minimizing modifiable risk factors may improve outcomes in living‐donor kidney transplantation.     

The relative importance of donor age in deceased and living donor kidney transplantation

In deceased donor kidney transplantation donor age is known to influence graft survival. The influence of living donor age on graft survival is questioned. We compared the influence of living and deceased donor age on the outcome of renal transplantation. All 1821 transplants performed in our center between 1990 and 2009 were included in the analysis. Observation was until April 2012. A total of 941 patients received a deceased donor kidney and 880 a living donor kidney. In multivariate Cox analysis, recipient age, maximum and current panel reactive antibodies, transplant year, HLA‐mismatches, donor age, donor gender, donor type, delayed graft function, and calcineurin inhibitor (CNI) and prednisone as initial immunosuppression were found to have a significant influence on death‐censored graft failure. The influence of both living and deceased donor age followed a J‐shaped curve, above 30 years the risk increased with increasing age. Donor type and donor age had an independent influence. The graft failure risk of deceased donor transplantation is almost twice that of living donor transplantation so that a 60‐year‐old living donor kidney has the same graft failure risk as a 20‐year‐old deceased donor kidney.     

Renal transplantation with aged donors

Research indicates that aged heart-beating cadaveric donors cause greater risk factors in kidney transplantation. The influence of age on the outcome of non-heart-beating (NHB) cadaveric renal transplantations has not yet been clarified. From July 1986 to May 1999, 63 patients who received cadaveric renal transplantation at Osaka City University Hospital and Osaka City General Hospital were divided into two groups according to their age. Renal function and graft-survival rates of the two groups were compared. The mean values of nadir donor serum creatinine were significantly worse (P < 0.05) in the aged donor group. In the aged donor group the percentage of immediately functioning grafts was lower and the percentage of non-functioning grafts was higher. During the first 10 years post-transplant, graft survival in the aged donor group was significantly lower than that in the younger donor group. We conclude that cadaveric renal transplantation from NHB aged donors can be to the detriment of renal function and graft survival rates compared to transplantation from younger donors.     

Results of Kidney Transplantation From Donors After Cardiac Death

Confronting the organ donor shortage, many transplant centers around the world increasingly use donors after cardiac death (DCD). Over the past 20 years, follow-up studies in kidney recipients comparing DCD and donors after brain death (DBD) have shown comparable long-term graft function and survival. As a consequence, DCD programs should be continued and expanded, for these donors constitute a potential solution to the imbalance between the numbers of end-stage kidney disease patients on waiting lists versus available kidney grafts. DCD kidneys do not necessarily signify suboptimal grafts; they may merit to be allocated the same as DBD grafts.     

Simultaneous pancreas-kidney transplantation from donation after cardiac death: successful long-term outcomes

OBJECTIVE: The outcomes of simultaneous pancreas-kidney (SPK) transplantation with donor organs procured from donation after cardiac death (DCD) are compared with transplants performed with donor organs recovered from donation after brain death (DBD). SUMMARY BACKGROUND DATA: Concerns exist regarding the utilization of pancreata obtained from DCD donors. While it is known that DCD kidneys will have a higher rate of DGF, long-term functional graft survival data for DCD pancreata have not been reported. METHODS: A retrospective review of all DCD SPK transplants performed at a single center was undertaken. RESULTS: Patient, pancreas, and kidney survival at 5 years were similar between DCD and DBD organs. Pancreas function and outcomes were indistinguishable between the 2 modes of procurement. As expected, the DCD kidneys had an elevated rate of DGF, which had no significant long-term clinical impact. CONCLUSION: SPK transplantation using selected DCD donors is a safe and viable method to expand the organ pool for transplantation.     

Why should we implement living donation in renal transplantation?

BACKGROUND: Renal transplantation started with living donor transplants. However, after the introduction of cyclosporine, the improved results of kidney transplants from cadaveric donors have raised controversy regarding the use of living donors. There are various reasons as to why some transplant centers tend to refuse living donation: first of all, the possibility that unilateral nephrectomy can be harmful to a healthy individual. SUBJECTS AND METHODS: By reviewing the medical literature on the various aspects of living donation, postoperative mortality in connection with living donation has been calculated to be 1:3,000. RESULTS: Long-term follow-up investigations of donors demonstrated that the risk of progressive renal failure, hypertension, and proteinuria was not increased by nephrectomy per se, but other causes were responsible for that in occasional patients. From these studies, one can conclude that unilateral nephrectomy is not harmful to a healthy individual. In addition, there are other valid reasons to expand living donation: 1) the need for cadaveric donor kidneys for transplantation far exceeding the supply; 2) the better kidney quality from living donors due to the shorter ischemia time, the lack ofagonal phase and cytokines release that follows brain death; 3) the continuing improved results of kidney transplants from living donors in comparison with those from cadaveric donors in the cyclosporine era also. This appears to be true also for kidney transplants from unrelated living donors in spite of complete incompatibility with recipients. 4) Pre-emptive transplantation, based on living donors, not only avoids the risks, cost, and inconvenience of dialysis, but is also associated with better graft survival than transplantation after a period of dialysis, particularly within the live donor cohort. CONCLUSIONS: In conclusion, living donor transplants should be part of any transplant center's activity. To encourage living donation, every center should have a formal recipient family education program in conjunction with national organ donation campaigns.     

Can a living kidney donor become a kidney recipient?

The living kidney donor represents a good resource for kidney transplantation. These grafts display better function and long-term graft survival at 5 and 10 years of follow-up. Furthermore, living donors prefer the possibility to increase kidney donation for a large waiting list of patients with end-stage renal disease (ESRD). However, kidney donation is a major surgical procedure associated with benefits and risks. The risks of donation have been studied in large series of living donors to focus on morbidity and mortality rates associated with the surgical procedure. New surgical laparoscopic techniques promote living kidney donation. While the benefits to the recipient are obvious, those for the donor are subjective and not quantifiable. However, donors describe donation as a great experience in life. The risk of kidney donation may be divided into the perioperative and the long-term risks. The evaluate the long-term risks for kidney donors requires a long follow-up. The main source of kidney donors in our transplant center has been living-related and -unrelated donors, with a minor percentage of cadaveric donors. In this report we present four kidney donors who developed ESRD thereafter, three becoming kidney recipients.     

Outcomes of Renal Transplantation Following Bone Marrow Transplantation

This single center retrospective study was undertaken to determine the outcome of kidney transplantation (KT) after bone marrow transplantation (BMT) and also to determine the need for immunosuppressive therapy after KT when the BMT marrow donor is the KT donor. Kidney transplantation was performed in 10 patients with BMT nephropathy (BMTN). In six patients, the KT donor was the BMT donor; these individuals were given no long-term immunosuppression. Four other patients received KT from donors who were not the marrow donor (two living donors, two cadaveric donors). After median follow up of 34 months, no patient had an episode of acute rejection. All graft losses (n = 4) resulted from patient death. Three were because of infectious processes, including two infectious deaths in patients not on immunosuppression. Median estimated actuarial patient and graft survival (Kaplan-Meier) was 105 months. We conclude that patients with BMTN who receive KT from their marrow donor do not require immunosuppression. Whether immunosuppressive therapy is given or not, outcome appears to be determined largely by BMT-related immune dysfunction.     

Outcomes of Pancreas Transplantation in the United States Using Cardiac-Death Donors

Organs donated after cardiac death (DCD) are used to expand the donor pool. We analyzed the outcomes in the United States of pancreatic transplantation of organs from DCD donors performed between 1993 and 2003.
We used the OPTN/UNOS Registry to compare outcomes of primary pancreas allografts from DCD donors and donors after brain death (DBD). The primary endpoints were graft failure and patient death. A national survey regarding the use of DCD donors in pancreas transplantation was conducted among the directors of pancreas transplant centers.
Data were obtained on 47 simultaneous pancreas-kidney transplants (SPK) and 10 solitary pancreas transplants from DCD donors and on 2431 SPK and 1607 solitary pancreas transplants from DBD donors. Recipients of a SPK transplants from DCD and DBD donors had equivalent patient and graft survival rates at 1, 3 and 5 years. For recipients of SPK transplants, the wait for organs from DCD donors was significantly shorter than that for organs from DBD donors. SPK recipients of organs from DCD donors had longer hospital stays than did recipients of organs from DBD donors. With renal allografts, the incidence of delayed graft function was almost four times higher with organs from DCD donors than with organs from DBD donors.
Selective use of organs from DCD donors is safe for pancreas transplantation.     

供肝短缺形势下的我国肝移植策略

近5年来我国肝移植发展非常迅速,然而,供肝短缺成为制约临床肝移植发展的瓶颈。因此,拓展供肝来源成为目前肝移植临床的重点。活体肝移植在尸体供肝受限的情况下可以很好地扩展供肝来源,且活体供肝具有活力强、冷缺血时间短等优势;劈裂式肝移植可增加15％～28％的供肝数量,有望成为解决供肝短缺的主要手术方式之一;脑死亡供者在西方国家是移植器官的主要来源,在我国亦有广大的应用前景,但脑死亡供者器官移植刚刚起步,有许多问题亟待研究;此外,边缘供肝,包括脂肪变性肝脏、HBsAg阳性肝脏、超过60岁的高龄供者捐献的肝脏、冷缺血时间超过14h的盱脏等均可用以缓解日益突出的供肝短缺矛盾。     

Kidney transplantation in the Hispanic population

Hispanic race and low socioeconomic status are established predictors of disparity in access to kidney transplantation. This single‐center retrospective review was undertaken to determine whether Hispanic race predicted kidney transplant outcomes. A total of 720 patients underwent kidney transplantation from January 1, 2004 to December 31, 2013, including 398 Hispanic patients and 322 non‐Hispanic patients. Hispanic patients were significantly younger (p < 0.0001), on hemodialysis for longer (p = 0.0018), had a greater percentage with public insurance (p < 0.0001), more commonly had diabetes as the cause of end‐stage renal disease (p = 0.0167), and had a lower percentage of living donors (p = 0.0013) compared to non‐Hispanic patients. There was no difference in one‐, five‐, and 10‐yr graft (97%, 81%, and 61% vs. 95%, 76%, and 42% p = 0.18) or patient survival (98%, 90%, and 84% vs. 97%, 87%, and 69% p = 0.11) between the Hispanic and non‐Hispanic recipients. Multivariate analysis identified increased recipient age and kidney donor profile index to be predictive of lower graft survival and increasing recipient age to be predictive of lower patient survival. In the largest single‐center study on kidney transplantation outcomes in Hispanic patients, there is no difference in graft and recipient survival between Hispanic and non‐Hispanic kidney transplant patients, and in multivariate analysis, Hispanic race is not a risk factor for graft or patient survival.     

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.     

Similar Outcomes of Kidney Transplantations Using Organs From Donors After Cardiac Death and Donors After Brain Death

Background

To increase the number of cadaveric kidney transplants in Japan, it is necessary to proactively use organs from all donors. Since the revision of the Organ Transplant Law, the number of organ donors after cardiac death (DCD) has decreased but the number of organ donors after brain death (DBD) has increased; however, the number of donor organs and awareness of cadaveric transplantation have increased.

The Impact of Donor Factors on Early Graft Function in Kidney Transplantation From Donation After Cardiac Death

Donation after cardiac death (DCD) has the potential to significantly increase the number of organ donors. In this study, we investigate the influence of several donor parameters on the early graft function in kidney transplantation from DCD donors. We performed 58 kidney transplantations from DCD donors. Recipients were divided into 2 groups according to their graft function: normal graft function (NGF), patients who became be free of hemodialysis within 14 days post-transplantation) and delayed graft function (DGF) group, patients who required hemodialysis for longer than 15 days after transplantation). We compared donor age, sex, cause of death, warm and total ischemic time, duration of anuria (urine volume < 10 mL/h), and low blood pressure (systolic blood pressure < 60 mm Hg), usage of catecholamine and vasopressin, serum creatinine on the day of admission and graft retrieval, serum sodium concentration, and body temperature between 2 groups. The number of recipients in NGF and DGF group was 41 and 17. Univariate analysis revealed that duration of anuria (<24 vs ≥24 hours) and usage of catecholamine significantly influenced graft function. Duration of anuria was an independent risk factor for early graft function by multivariate analysis. In cadaveric kidney transplantation from DCD donors, there was a trend to poorer early graft function with donors who suffered from anuria for longer than 24 hours before kidney retrieval.     

Ureteric complications in recipients of kidneys from donation after circulatory death donors

A large increase in the use of kidneys from donation after circulatory death (DCD) donors prompted us to examine the impact of donor type on the incidence of ureteric complications (UCs; ureteric stenosis, urinary leak) after kidney transplantation. We studied 1072 consecutive kidney transplants (DCD n=494, live donor [LD] n=273, donation after brain death [DBD] n=305) performed during 2008‐2014. Overall, there was a low incidence of UCs after kidney transplantation (3.5%). Despite a trend toward higher incidence of UCs in DCD (n=22, 4.5%) compared to LD (n=10, 3.7%) and DBD (n=5, 1.6%) kidney transplants, donor type was not a significant risk factor for UCs in multivariate analysis (DCD vs DBD HR: 2.33, 95% CI: 0.77‐7.03, P=.13). There was no association between the incidence of UCs and donor, recipient, or transplant‐related characteristics. Management involved surgical reconstruction in the majority of cases, with restenosis in 2.7% requiring re‐operation. No grafts were lost secondary to UCs. Despite a significant increase in the number of kidney transplants from DCD donors, the incidence of UCs remains low. When ureteric complications do occur, they can be treated successfully with surgical reconstruction with no adverse effect on graft or patient survival.