Donation After Cardiac Death Kidneys Research Articles

ASTS Recommended Practice Guidelines for Controlled Donation after Cardiac Death Organ Procurement and Transplantation

The American Society of Transplant Surgeons (ASTS) champions efforts to increase organ donation. Controlled donation after cardiac death (DCD) offers the family and the patient with a hopeless prognosis the option to donate when brain death criteria will not be met. Although DCD is increasing, this endeavor is still in the midst of development. DCD protocols, recovery techniques and organ acceptance criteria vary among organ procurement organizations and transplant centers. Growing enthusiasm for DCD has been tempered by the decreased yield of transplantable organs and less favorable posttransplant outcomes compared with donation after brain death. Logistics and ethics relevant to DCD engender discussion and debate among lay and medical communities. Regulatory oversight of the mandate to increase DCD and a recent lawsuit involving professional behavior during an attempted DCD have fueled scrutiny of this activity. Within this setting, the ASTS Council sought best-practice guidelines for controlled DCD organ donation and transplantation. The proposed guidelines are evidence based when possible. They cover many aspects of DCD kidney, liver and pancreas transplantation, including donor characteristics, consent, withdrawal of ventilatory support, operative technique, ischemia times, machine perfusion, recipient considerations and biliary issues. DCD organ transplantation involves unique challenges that these recommendations seek to address.

The deceased donor score system in kidney transplants from deceased donors after cardiac death

A clinical score to identify kidneys from donors after cardiac death (DCD) with a high risk of dysfunction following transplantation could be a useful tool to guide the introduction of new algorithms for the preservation of these organs and improve their outcome after transplantation. We investigated whether the deceased donor score (DDS) system could identify DCD kidneys with higher risk of early post-transplant dysfunction. The DDS was validated in a cohort of 168 kidney transplants from donors after brain death (DBD) and then applied to a cohort of 56 kidney transplants from DCD. In the DBD cohort, the DDS grade predicted the incidence of delayed graft function (DGF) and levels of serum creatinine at 3 and 12 months post-transplant. Similarly, in the DCD cohort, the DDS grade correlated with DGF and also predicted the levels of serum creatinine at 3 and 12 months. Interestingly, the DDS identified a subgroup of marginal DCD kidneys in which minimization of cold ischemia time produced better early clinical outcome. These results highlight the impact of early interventions on clinical outcome of marginal DCD kidneys and open the possibility of using the DDS to identify those kidneys that may benefit most from therapeutic interventions before transplantation.

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

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. 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. 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. 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.

Substance Abuse Treatment Continuum in the North Carolina Department of Correction

The continuing shortage of kidneys for transplantation requires major efforts to expand the donor pool. Donation after cardiac death (DCD) increases the number of available kidneys, but it is unknown whether patients who receive a DCD kidney live longer than patients who remain on dialysis and wait for a conventional kidney from a brain-dead donor (DBD). This observational cohort study included all 2575 patients who were registered on the Dutch waiting list for a first kidney transplant between January 1, 1999, and December 31, 2004. From listing until the earliest of death, living-donor kidney transplantation, or December 31, 2005, 459 patients received a DCD transplant and 680 patients received a DBD transplant. Graft failure during the first 3 months after transplantation was twice as likely for DCD kidneys than DBD kidneys (12 *versus* 6.3%; *P* = 0.001). Standard-criteria DCD transplantation associated with a 56% reduced risk for mortality (hazard ratio 0.44; 95% confidence interval 0.24 to 0.80) compared with continuing on dialysis and awaiting a standard-criteria DBD kidney. This reduction in mortality translates into 2.4-month additional expected lifetime during the first 4 years after transplantation for recipients of DCD kidneys compared with patients who await a DBD kidney. In summary, standard-criteria DCD kidney transplantation associates with increased survival of patients who have ESRD and are on the transplant waiting list.

Histological Assessment of Preimplantation Biopsies May Improve Selection of Kidneys from Old Donors After Cardiac Death

Kidneys from old donors after cardiac death (DCD) may increase the donor pool but the prognosis of these kidneys is unsatisfactory. To improve these results, we retrospectively evaluated the diagnostic utility of published selection algorithms for old donor kidneys. We studied all DCD kidney transplantations between January 1, 1994 and July 1, 2005 at our institution (n = 199). Selection algorithms were evaluated in the subset of kidney transplantations from donors aged 60 years or older (n = 52). For histological assessment of kidney biopsies, glomerulosclerosis, tubular atrophy, interstitial fibrosis and vascular narrowing were blindly scored. Functional kidney weight was calculated as renal mass multiplied by the fraction of nonsclerosed glomeruli. Graft function and survival of kidneys from DCD aged 60 years or older were inferior to those from younger DCD. Histological scores were associated with kidney function and graft survival of old DCD kidney transplantations. Functional kidney weight was associated with kidney function but not graft survival, while donor glomerular filtration rate (GFR), donor age and machine perfusion characteristics were associated with neither of the clinical outcomes of interest. We conclude that histological assessment of preimplantation biopsies may improve the selection of kidneys from old DCD and may therefore contribute to expansion of the donor pool.

Donor Postextubation Hypotension and Age Correlate With Outcome After Donation After Cardiac Death Transplantation

Compared with standard donors, kidneys recovered from donors after cardiac death (DCD) exhibit higher rates of delayed graft function (DGF), and DCD livers demonstrate higher rates of biliary ischemia, graft loss, and worse patient survival. Current practice limits the use of these organs based on time from donor extubation to asystole, but data to support this is incomplete. We hypothesized that donor postextubation parameters, including duration and severity of hemodynamic instability or hypoxia might be a better predictor of subsequent graft function. We performed a retrospective examination of the New England Organ Bank DCD database, concentrating on donor factors including vital signs after withdrawal of support. Prolonged, severe hypotension in the postextubation period was a better predictor of subsequent organ function that time from extubation to asystole. For DCD kidneys, this manifested as a trend toward increased DGF. For DCD livers, this manifested as increased rates of poor outcomes. Maximizing the predictive value of this test in the liver cohort suggested that greater than 15 min between the time when the donor systolic blood pressure drops below 50 mm Hg and flush correlates with increased rates of diffuse biliary ischemia, graft loss, or death. Donor age also correlated with worse outcome. Time between profound instability and cold perfusion is a better predictor of outcome than time from extubation to asystole. If validated, this information could be used to predict DGF after DCD renal transplant and improve outcomes after DCD liver transplant.

EFFECT OF MULTIORGAN DONATION AFTER CARDIAC DEATH RETRIEVAL ON LUNG PERFORMANCE

For donation after cardiac death (DCD) transplantation to achieve its full potential, multiorgan retrieval is desirable. Although there are several novel individual techniques recently described for DCD lung donation, they have not been evaluated or compared in a DCD multiorgan scenario. This study describes (i) the technical aspects and (ii) early lung and abdominal organ performance of several combinations of DCD donor liver, kidney and lung retrieval techniques that would mimic common DCD clinical scenarios. Lung oxygenation, urine production, bile production and biochemical measures were assessed as the outcome of a complex ex vivo lung, liver and kidney perfusion DCD model. Successful ex vivo multiorgan perfusion was possible following the three retrieval techniques tested, with excellent oxygenation over a 2-h assessment period, identical to prior studies where the lungs were tested alone. Multiorgan DCD retrieval, including lungs of good quality, is possible from a variety of clinical scenarios and should therefore be considered with all DCD retrieval opportunities.

Experience in Renal and Extrarenal Transplantation with Donation after Cardiac Death Donors with Selective Use of Extracorporeal Support

Most reports of donation after cardiac death (DCD) donors are exclusive to kidney transplantation and report high rates of delayed graft function (DGF). 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. 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). 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.

Serum Neutrophil Gelatinase-Associated Lipocalin as a Predictor of Organ Recovery from Delayed Graft Function after Kidney Transplantation from Donors after Cardiac Death

Because of a worldwide shortage of renal grafts, kidneys procured from donors after cardiac death (DCD) have recently become an important source of renal transplants. However, DCD kidneys often have complications with delayed graft function (DGF) and recipients require hemodialysis (HD) in the early period after kidney transplantation (KTx). This study evaluated serum NGAL as a potential specific parameter to predict early functional recovery of transplanted DCD kidneys. The average serum neutrophil gelatinase-associated lipocalin (NGAL) level in normal samples was 53 +/- 30 ng/ml, while that in patients with chronic renal failure requiring HD was markedly raised at 963 +/- 33 ng/ml. In patients undergoing a living-related KTx from a living donor (n=11), serum NGAL level decreased rapidly after KTx, and only in two cases, with serum NGAL levels over 400 ng/ml on postoperative day 1 (POD1), was HD required due to DGF. In contrast, all patients undergoing a KTx from a DCD (n=5) required HD due to DGF. Even in these cases, serum NGAL levels decreased rapidly several days after a KTx prior to the recovery of urine output and preceding the decrease in serum creatinine level. The pattern of decline in serum NGAL was biphasic, the decrease after the second peak indicating a functional recovery within the next several days. These data suggest that monitoring of serum NGAL levels may allow us to predict graft recovery and the need for HD after a KTx from a DCD.

Outcome of Kidney Transplantation Using Expanded Criteria Donors and Donation After Cardiac Death Kidneys: Realities and Costs

Expanded criteria donors (ECDs) and donation after cardiac death (DCD) provide more kidneys in the donor pool. However, the financial impact and the long-term benefits of these kidneys have been questioned. From 1998 to 2005, we performed 271 deceased donor kidney transplants into adult recipients. There were 163 (60.1%) SCDs, 44 (16.2%) ECDs, 53 (19.6%) DCDs and 11 (4.1%) ECD/DCDs. The mean follow-up was 50 months. ECD and DCD kidneys had a significantly higher incidence of delayed graft function, longer time to reach serum creatinine below 3 (mg/dL), longer length of stay and more readmissions compared to SCDs. The hospital charge was also higher for ECD, ECD/DCD and DCD kidneys compared to SCDs, primarily due to the longer length of stay and increased requirement for dialysis (70,030 dollars, 72,438 dollars, 72,789 dollars and 47,462 dollars, respectively, p < 0.001). Early graft survival rates were comparable among all groups. However, after a mean follow-up of 50 months, graft survival was significantly less in the ECD group compared to other groups. Although our observations support the utilization of ECD and DCD kidneys, these transplants are associated with increased costs and resource utilization. Revised reimbursement guidelines will be required for centers that utilize these organs.

In Situ Preservation of Kidneys From Donors After Cardiac Death

To describe the results and complications of in situ preservation (ISP) of kidneys from donors after cardiac death (DCD). DCD donors are increasingly being used to expand the pool of donor kidneys. ISP reduces warm ischemic injury which is associated with DCD donation. Insertion of a double-balloon triple-lumen catheter allows selective perfusion of the abdominal aorta to preserve the kidneys in situ. From January 2001 until August 2005, 133 ISP procedures were initiated in our procurement area. Fifty-six (42%) ISP procedures led to transplantation; in the remaining 77 cases (58%), the donation procedure was abandoned or both kidneys were discarded because of ISP complications (n = 31), poor graft quality (n = 23), no consent for donation (n = 13), medical contraindications (n = 8), or unknown cause (n = 2). Increasing donor age (odds ratio (OR) 1.06 per year, P < 0.001) and uncontrolled DCD donation (OR 5.4, P < 0.001) were independently correlated with ISP complications. After transplantation, prolonged double-balloon triple-lumen catheter insertion time was an independent predictor of graft failure (OR 2.0, P = 0.05). Selected controlled DCD donors were managed by rapid laparotomy and direct aortic cannulation; graft survival of these kidneys was superior to kidneys from controlled DCD donors managed by ISP. A minority of initiated ISP procedures led to transplantation, resulting in a high workload compared with donation after brain death. The association between increasing catheter insertion time and inferior graft outcome emphasizes the need for fast and effective surgery. Therefore, rapid laparotomy with direct aortic cannulation is preferred over ISP in controlled DCD donation. Despite these limitations, we have expanded our donor pool 3- to 4-fold by procuring DCD kidneys that were preserved in situ.

Controlled donation after cardiac death: a European perspective

Terminally ill patients who do not meet brain death criteria and die of cardiac arrest after withdrawal of life support may be considered as potential organ donors: such donors are referred to as controlled donors after cardiac death (DCD). Controlled DCD donors are increasingly being used in Northern Europe and the United States in an effort to expand the donor pool. Ethical concerns regarding the diagnosis of death based on cardiopulmonary rather than neurological criteria have largely been resolved over the past decade. Follow-up studies of recipients by several transplant centers have shown that functioning controlled DCD kidneys are equivalent to kidneys from conventional brain-dead donors with respect to long-term prognosis. Concerns about long-term repercussions for the higher incidence of delayed graft function with DCD kidneys are not supported by the current evidence. The donor pool may be further expanded by transplanting selected kidneys from older DCD, in particular for the increasing population of older kidney transplant candidates. Successful transplantation of these delicate organs is possible when donors and recipients are carefully managed by well-trained, motivated, and effectively collaborating transplant personnel.

Outcomes of Kidneys from Donors After Cardiac Death: Implications for Allocation and Preservation

Although donation after cardiac death (DCD) kidneys have a high incidence of delayed graft function (DGF) and have been considered marginal, no tool for stratifying risk of graft loss nor a specific policy governing their allocation exist. We compared outcomes of 2562 DCD, 62,800 standard criteria donor (SCD) and 12,812 expanded criteria donor (ECD) transplants reported between 1993 and 2005, and evaluated factors associated with risk of graft loss and DGF in DCD kidneys. Donor age was the only criterion used in the definition of ECD kidneys that independently predicted graft loss among DCD kidneys. Kidneys from DCD donors <50 had similar long-term graft survival to those from SCD (RR 1.1, p = NS). While DGF was higher among DCD compared to SCD and ECD, limiting cold ischemia (CIT) to <12 h decreased the rate of DGF 15% among DCD <50 kidneys. These findings suggest that DCD <50 kidneys function like SCD kidneys and should not be viewed as marginal or ECD, and further, limiting CIT <12 h markedly reduces DGF.

Using livers from donation after cardiac death donors—A proposal to protect the true Achilles heel

As the waiting list for organ transplant continues to increase (over 90,000 candidates as of May 30, 2007), the pressure to increase the number of donor organs is the impetus to expand the use of organs from donation after cardiac death (DCD) donors. The focus on DCD, previously referred to as non–heart-beating donor (NHBD), has led to significant increases in its utilization (Table 1), although the contribution to the donor pool remains only 7% in the United States and is disproportionately reflected in increased kidney transplants (Table 2). Prior to the acceptance of brain death, donors were required to have cessation of heart function in order to procure organs for transplantation. In some areas where brain death legislation has not been widely adopted, such as Asia, DCD represents a significant source of organs for transplantation. Although the Maastricht Conference on DCD in 1994 identified 4 categories of DCD [Category I: dead on arrival; Category II: unsuccessful resuscitation; Category III: waiting cardiac death; and Category IV: cardiac death in a braindead donor], it is easier to envision DCD based on two distinct populations, one following uncontrolled cardiopulmonary arrest (Categories I and II) and the other under conditions of controlled removal from life support, without the criteria for brain death being fulfilled. In 1995, the University of Pittsburgh provided one of the earliest comparisons between controlled and uncontrolled DCD. There were 24 DCD livers, 14 in the uncontrolled group (Group 1) and 10 in the group in which controlled termination of life support was performed in the operating room (Group 2). Of the liver grafts that were used, the immediate graft function rate was 50% (3/6) in Group 1 and 100% (6/6) in Group 2; however, the overall 2-year patient and graft survival was only 58% and 33%, respectively. In order to improve outcomes with DCD donors, the decision was made to avoid using uncontrolled DCD livers and, with further experience, to more carefully control risk factors [e.g., avoidance of old ( 60 year old) DCD donors, avoidance of donors with long ( 60 minutes) warm ischemic times during procurement, avoidance of confounding factors in the DCD donors, and minimization of cold ischemic times]. While patient survival and graft survival have improved in more recent eras, the impact of DCD on liver transplantation, as assessed from the Scientific Registry of Transplant Recipients (SRTR) database, shows that DCD graft survival was significantly lower than that of donation after brain death (DBD) grafts, with 1and 3-year graft survival of 70.2% and 63.3% for DCD recipients versus 80.4% and 72.1% for recipients of livers from conventional DBD donors. Recipients of a DCD graft had a greater incidence of primary nonfunction (11.8 versus 6.4%) and retransplantation (13.9% versus 8.3%) compared with DBD recipients. Similar findings have also been reported at single centers 12,13 The mandated period of warm ischemia imposed during the process of certifying death in controlled DCD leads to stagnation of blood in the microcirculation.

Up-Regulation of Osteopontin, Chemokines, Adhesion Molecule, and Heat Shock Proteins in 1-Hour Biopsy From Cardiac Death Donor Kidneys

Aims Since April 1979, 471 kidneys were retrieved from donors after cardiac death (DCD) using an in situ regional cooling technique, with excellent renal function and good long-term graft survival. However, the precise cascade of events following transplantation of DCD kidneys and the influence of ischemia-reperfusion injury remain unclear. In this study, we performed gene expression profiling using 1-hour biopsy samples from DCD kidneys versus those from living sources. Methods All kidney grafts were procured at our center using an in situ regional cooling technique from DCD. Living donor kidneys (LD) were harvested by open nephrectomy. All graft biopsies were performed 1 hour after reperfusion (DCD n = 8, LD n = 9). We analyzed the expression profile of 20,173 genes. Results One hundred seventy eight genes were up-regulated (>2-fold difference and DCD/LD > 1.5) and 120 down-regulated (<1/2-fold and LD/DCD > 1.5) in DCD kidneys. Expression of osteopontin (22.5 ± 2.6–fold DCD vs 7.7 ± 1.7 LD; P < .001), chemokines (CCL4 4.4 ± 0.7 vs 2.5 ± 0.3; P < .01), (CCL2 6.0 ± 1.3 vs 2.8 ± 0.5), CXCL1 (9.5 ± 0.4 vs 2.0 ± 0.2), and CXCL2 (16.7 ± 5.3 vs 4.8 ± 1.3; P < .05), adhesion molecule (ICAM-1 4.7 ± 0.7 vs 2.5 ± 0.4; P < .05), and heat shock proteins (HSPA1L 6.7 ± 0.7 vs 1.6 ± 0.3, HSPA1A 17.7 ± 2.6 vs 2.4 ± 0.5, HSPA1B 13.3 ± 0.2 vs 3.0 ± 0.7, HSPA5 6.7 ± 0.8 vs 3.2 ± 0.3, HSPB1 2.9 ± 0.2 vs 1.0 ± 0.1, and HSPH1 19.4 ± 3.0 vs 5.9 ± 1.1; P < .001) were up-regulated in the kidneys from DCD. Conclusion This report analyzed global gene expression using 1-hour biopsy samples from DCD kidneys. These results may provide new insight into the identification of novel target genes for the development of therapeutic approaches and for determining graft viability of kidneys from DCD.

Recent Trends and Results for Organ Donation and Transplantation in the United States, 2005

Recent Trends and Results for Organ Donation and Transplantation in the United States, 2005

Simultaneous Pancreas-Kidney Transplantation From Donation After Cardiac Death

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). 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. A retrospective review of all DCD SPK transplants performed at a single center was undertaken. 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. SPK transplantation using selected DCD donors is a safe and viable method to expand the organ pool for transplantation.