The D&T report

Quality of Life and Depression in CKD: Improving Hope and Health

To determine the effect of donation after cardiac death (DCD) livers on post-transplantation costs. DCD livers are increasingly being used to expand the donor pool despite higher complication rates. Although complications after liver transplantation have profound financial implications, the effect of DCD livers on post-transplantation costs has not been studied. We estimated direct medical care costs based on inpatient and outpatient hospital costs for 28 DCD and 198 donation after brain death (DBD) liver recipients. Organ acquisition and physician costs were excluded. Donor and recipient demographics were comparable for DCD and DBD transplants. One-year, post-transplantation costs were higher for DCD recipients (124.9% of DBD costs, P = 0.04). DCD costs remained higher (125.2% of DBD costs, P = 0.009) after adjusting for recipient characteristics. Furthermore, DCD post-transplantation costs were 30% higher than DBD costs after adjusting for pre-transplantation costs (P = 0.02). Biliary complications (DCD 58% vs. DBD 21%; P < 0.001) and, specifically, ischemic cholangiopathy (DCD 44% vs. DBD 1.6%; P < 0.001) occurred more frequently after DCD transplantation. Moreover, DCD recipients underwent retransplantation more often (DCD 21% vs. DBD 7.1%, P = 0.02). One-year costs were increased for recipients with ischemic cholangiopathy or retransplantation by 53% (P = 0.01) and 107% (P < 0.001), respectively. However, DCD costs continued to be higher when retransplanted patients were excluded (120% of DBD costs, P = 0.02). Higher rates of graft failure and biliary complications translate into markedly increased direct medical care costs for DCD recipients. These important financial implications should be considered in decisions regarding the use of DCD livers.

One of the main factors limiting potential uptake of pancreas transplantation, particularly in the United Kingdom, is the shortage of grafts. There has therefore been a recent expansion, particularly in the United Kingdom, in the utilization of grafts from donation after cardiac death (DCD) donors. These grafts are subjected to a greater ischemic insult and are arguably at higher risk of poor functional outcome. Although conventional preservation techniques may be adequate for donation after brain death (DBD) and low-risk DCD pancreases, as the number of DCD pancreas transplants increase and the threshold for rejecting organs decreases, the importance of optimal preservation techniques is going to increase. Over recent years, there have been significant advances in preservation techniques for DCD kidneys, improving the outcome of these marginal grafts. However, the use of such techniques for pancreas preservation is extremely limited and mainly historical. This overview describes the background and results of the established method of pancreas preservation for DBD, namely, cold static storage, and describes the use of the two-layer method. It also reviews pulsatile machine perfusion and normothermic perfusion for pancreas preservation techniques, which have shown promise in the preservation of DCD kidney grafts. The use of these techniques in pancreas preservation is predominantly historical but warrants reevaluation as to the feasibility of applying these techniques to DCD pancreas grafts not only for preservation but also for viability assessment. Further areas for development of pancreas preservation are discussed.

Bone Marrow Iron in CKD: Correlation With Functional Iron Deficiency

To determine whether the outcomes of liver transplantation (LTx) from donation after cardiac death (DCD) donors are equivalent to those from donation after brain death (DBD) donors. Because of the significant donor organ shortage, more transplant centers are using livers recovered from DCD donors. However, long-term, single-center outcomes of liver transplantation from DCD donors are limited. From January 1, 1993, to July 31, 2002, 553 liver transplants were performed from DBD donors and 36 were performed from DCD donors. Differences in event rates between the groups were compared with Kaplan-Meier estimates and the log-rank test. Differences in proportion and differences of means between the groups were compared with Fisher exact test and the Wilcoxon rank sum test, respectively. Mean warm ischemic time at recovery in the DCD group was 17.8 +/- 10.6 minutes. The overall rate of biliary strictures was greater in the DCD group at 1 year (33% versus 10%) and 3 years (37% versus 12%; P = 0.0001). The incidence of hepatic artery thrombosis, portal vein stenosis/thrombosis, ischemic-type biliary stricture (ITBS), and primary nonfunction were similar between groups. However, the incidence of both hepatic artery stenosis (16.6% versus 5.4%; P = 0.001) and hepatic abscess and biloma formation (16.7% versus 8.3%; P = 0.04) were greater in the DCD group. Trends toward worse patient and graft survival and increased incidence of ITBS were seen in DCD donors greater than 40 years compared with DCD donors less than 40 years. Overall patient survival at 1 year (DCD, 80%; versus DBD, 91%) and 3 years (DCD, 68%; versus DBD, 84%) was significantly less in the DCD group (P = 0.002). Similarly, graft survival at 1 year (DCD, 67%; versus DBD, 86%) and 3 years (DCD, 56%; versus DBD, 80%) were significantly less in the DCD group (P = 0.0001). Despite similar rates of primary nonfunction, LTx after controlled DCD resulted in worse patient and graft survival compared with LTx after DBD and increased incidence of biliary complications and hepatic artery stenosis. However, overall results of LTx after controlled DCD are encouraging; and with careful donor and recipient selection, LTx after DCD may successfully increase the donor liver pool.

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.

Renal transplantation improves survival of patients with end-stage kidney disease (ESKD) (Wolfe, McCullough et al. 2009). In most countries, including the United States and Australia, there continues to be a growing disparity between the limited availability of deceased-donor kidneys compared to potential transplant candidates. In contrast, livedonor kidney transplantation has been steadily increasing over time. It has been well established that the type (live or deceased donor kidneys) and quality (donor age and presence of donor comorbidities) of donor kidneys have a significant impact on renal allograft outcomes. In this chapter, we will focus on both live-donor and deceased donor kidney transplantation and the impact of donor factors and types on graft and patient outcomes. With the continuing shortage of deceased donor kidneys coupled with a growing number of older transplant candidates, there has been a greater acceptance of using older donor kidneys, including increased utility of expanded criteria donor (ECD) and donation after cardiac death (DCD) kidneys. We will look at the impact of using ECD and DCD kidneys on graft and patient survival, and to identify modifiable factors that may improve transplant outcomes in recipients receiving ECD and DCD kidneys. Finally, we will discuss whether the implementation of utility-based allocation strategies for deceased donor kidneys is an appropriate way forward to provide a balance between utility and equity in the distribution of deceased donor kidneys.

Is liver transplantation using organs donated after cardiac death cost‐effective or does it decrease waitlist death by increasing recipient death?

There is continuing disparity between demand for and supply of kidneys for transplantation. This review describes the current state of kidney donation after cardiac death (DCD) and provides recommendations for a way forward. The conversion rate for potential DCD donors varies from 40%-80%. Compared to controlled DCD, uncontrolled DCD is more labour intensive, has a lower conversion rate and a higher discard rate. The super-rapid laparotomy technique involving direct aortic cannulation is preferred over in situ perfusion in controlled DCD donation and is associated with lower kidney discard rates, shorter warm ischaemia times and higher graft survival rates. DCD kidneys showed a 5.73-fold increase in the incidence of delayed graft function (DGF) and a higher primary non function rate compared to donation after brain death kidneys, but the long term graft function is equivalent between the two. The cold ischaemia time is a controllable factor that significantly influences the outcome of allografts, for example, limiting it to < 12 h markedly reduces DGF. DCD kidneys from donors < 50 function like standard criteria kidneys and should be viewed as such. As the majority of DCD kidneys are from controlled donation, incorporation of uncontrolled donation will expand the donor pool. Efforts to maximise the supply of kidneys from DCD include: implementing organ recovery from emergency department setting; improving family consent rate; utilising technological developments to optimise organs either prior to recovery from donors or during storage; improving organ allocation to ensure best utility; and improving viability testing to reduce primary non function.

On Being Better Kidney Doctors: Understanding Trajectories, Probabilities, Predictability, and People

α-Klotho and Kidney Function Decline: An Important Step Forward in Understanding the Link Between Mineral Metabolism and Kidney Disease Progression

Liver transplantation (LT) from controlled donation after cardiac death (DCD) donors has increased steadily during the past decade because of the donor shortage in the United States. Although early reports of LT from DCD donors provided evidence for acceptable outcomes, long-term graft and patient survival rates from these procedures have been reviewed only recently. From February 1990 to June 2006, 1209 LTs were performed from donation after brain death (DBD) donors, and 24 were performed from DCD donors at our institution. Detailed review of donor and recipient characteristics, and survival rates were evaluated in the two groups. One- and 3-year patient survival was similar in both groups, (DCD 86.8%, 81.7% vs. DBD 84.0%, 76.0%, respectively; P=0.713). Graft survival appeared inferior in the DCD group compared with the DBD group at 1 year (69.1% vs. 78.7%) and 3 years (58.6% vs. 70.2%), but there was no statistical difference (P=0.082). There were no significant differences in hepatic artery thrombosis, portal vein thrombosis, primary nonfunction, and biliary stricture between the two groups. All cases with biliary stricture in DCD group finally led to graft loss, and all survived with retransplantation. The outcome of LT from DCD donors remains acceptable in our institution. Although biliary complication rate was similar in two groups, the consequence of this complication in DCD was more severe and often led to graft loss. Close observation of biliary complications after LT from DCD donors would be beneficial.

Blood Pressure Goals: How Low Is Safe in CKD?

Cognitive Impairment in Dialysis Patients: Focus on the Blood Vessels?

Donation after cardiac death (DCD) is recognized as an important source of allografts to bridge the growing disequilibrium between the number of donors and recipients. Current transplant experience with DCD organs has focused on the adult recipient population, however little is known about the pediatric recipient experience. While there is increasing acceptance of these grafts in adults, transplant centers appear reluctant to use these grafts in the pediatric population. We reviewed the United Network for Organ Sharing database from 1995-2005 to determine the national experience with pediatric recipients of DCD organs. Among 4026 renal transplants performed in children 18 years and younger, 26 (0.6%) received a renal allograft from a DCD donor. Ten (38.5%) received kidney allografts from pediatric donors (age < or = 18) and 16 (61.5%) from adult donors (age > 18 years). Graft survival at one and five years was 82.5%, 74.3% for kidneys from DCD donors compared to 89.6%, 64.8% from brain dead donors (DBD) (P = 0.7). Among 4991 liver transplants, 19 (0.4%) were from DCD donors. Sixteen patients (84.2%) received livers from pediatric donors and three (15.8%) from adult donors. Graft survival at one and five years was 89.2%, 79.3% for livers from DCD, compared to 75.6%, 65.8% for DBD (P = 0.3). The use of DCD donors in the pediatric population is very limited; however graft survival is comparable to DBD grafts. Although pediatric centers may have been reluctant to utilize this donor source, this limited experience demonstrates that the select use of DCD organs can produce acceptable and durable graft survival in the pediatric population.