Expanded Criteria Donor Kidney Transplantation Research Articles

Matching “Engine and Chassis” in ECD Kidney Transplantation Using a Novel Creatinine Clearance Match Ratio (CCMR) Is Associated With Improved Outcomes.

BACKGROUND: To improve outcomes of expanded criteria donor (ECD) kidneys, prior studies matched donors to recipients according to recipient weight or donor kidney size. This study hypothesizes that matching donors to recipients based on Cockcroft-Gault estimates of creatinine clearance can improve outcomes in ECD kidney transplants compared to predictions based on size matching or donor creatinine clearance alone. METHODS: Recipients of ECD kidneys in the Scientific Registry of Transplant Recipients (SRTR) who were transplanted from October 1, 1987 to August 31, 2011 were included. The estimated creatinine clearance ratio (CCMR) was calculated as the estimated recipient creatinine clearance based on manipulations of the Cockcroft-Gault equation utilizing donor creatinine clearance at the time of transplant. Univariate and multivariate analyses predicted the hazard ratio of graft failure and the odds ratio of requiring dialysis within the first week. The CCMR was compared to the kidney donor risk index (KDRI) and recipient-to-donor weight and age ratios using discrimination analyses. RESULTS: 25,640 ECD kidney transplants were analyzed. On multivariate analysis, higher CCMR was associated with increased graft failure and odds of requiring dialysis within the first week (comparing highest ratio quintile versus lowest ratio quintile: HR 1.53, p<0.001; OR 2.18, p<0.001). CCMR was found to be superior in prediction and discrimination ability as compared to donor creatinine clearance, recipient/donor age ratio, and recipient/donor weight ratio. CONCLUSION: ECD kidneys have improved outcomes when the donor/recipient creatinine clearance match ratio is optimal.

Expanded Criteria Donors: The End of an Era.

Expanded criteria donor (ECD) kidneys increase the donor organ pool but their value has been questioned because of expected lower survival outcomes. With the development of the Kidney Donor Risk Index and a new allocation system, the end of the ECD kidney era is imminent. The study purpose was to retrospectively review our 12 year single center experience with ECD kidney transplants (KT). Methods: All patients (pts) received antibody induction with tacrolimus/mycophenolate ± steroids. Standardized management algorithms were implemented to preserve nephron function (including machine preservation) and pt selection was based on low immunological risk and predicted limited nephron need. Results: Over a 12 year period, we performed 1366 deceased donor KTs in adult pts including 468 (34%) from ECDs; 245 pts (53%) had at least 5 years follow-up. 36 KTs were from DCD/ECDs and 46 dual KTs were performed. With a mean follow-up of 4 years, actual pt survival was 75% and graft survival was 59%. 75 pts (16%) experienced death with a functioning graft (DWFG), so death-censored graft survival was 70%. One year pt and graft survival were 94% and 86%. Outcomes were analyzed according to recipient age categories (<50, n=70; 50-59, n=116; 60-69, n=185; >70, n=95). The incidence of primary nonfunction was slightly higher in the oldest and youngest (6%) compared to the 2 mid-age recipient categories (4%, p=NS). DWFGs were significantly higher in the oldest (22%) compared to the youngest recipient category (8.6%, p=0.03), whereas the incidence was intermediate (16%) in the 2 mid-age categories. One-year mortality was also higher in the oldest (9.5%) compared to the three younger recipient age categories (4.9%, p=0.09). Overall mortality rates increased with older age category from 19% in youngest to 28% in oldest recipients (p=NS). One year rates of graft loss were 12.3% in the 2 younger compared to 15% in the 2 older categories (p=NS). However, the overall rate of graft loss was 47% in the youngest compared to 40% in the 3 older categories (p=NS). Conclusions: By appropriate donor and recipient profiling and the use of management algorithms aimed at preserving renal function, acceptable intermediate-term outcomes can be achieved with ECD KTs irrespective of recipient age.

Unexplained Variation in Center Use of Expanded Criteria Donor Kidney Transplantation in the United States.

Unexplained Variation in Center Use of Expanded Criteria Donor Kidney Transplantation in the United States.

Machine perfusion versus static cold storage in expanded criteria donor kidney transplantation: 3-year follow-up data

Machine perfusion versus static cold storage in expanded criteria donor kidney transplantation: 3-year follow-up data

Impact of Cold Ischemia Time on Graft Survival Among ECD Transplant Recipients: A Paired Kidney Analysis

Delays in expanded criteria donor (ECD) kidney placement increases cold ischemia times (CIT) potentially leading to discard. The effect of increased CIT on ECD kidney transplant outcomes is unknown. We evaluated paired ECD kidneys (derived from the same donor transplanted to different recipients) from the SRTR registry transplanted between 1995 and 2009 (n = 17,514). To test the effect of CIT, we excluded paired transplants with the same CIT (n = 3286). Of 14,230 recipients (7115 donors) the median difference in CIT was 5 h (Q1 = 3 h, Q3 = 9 h). Delayed graft function (DGF) was significantly more likely between pairs with greater CIT (35% vs. 31%, p < 0.001) including substantially higher rates for CIT differences ≥ 15 h (42%). Overall graft loss was not significantly different between recipients with higher CIT relative to paired donor recipients with lower CIT (p = 0.47) or for pairs with differences of 1-3 h (p = 0.90), 4-9 h (p = 0.41), 10-14 h (p = 0.36) or ≥ 15 h (p = 0.10). Results were consistent in multivariable models adjusted for recipient factors. Although increasing cold ischemia time is a risk factor for DGF among ECD kidney transplants, there is no effect on graft survival which may suggest an important utility for donor kidneys that may not currently be considered viable.

Delayed Graft Function Decreases Early and Intermediate Graft Outcomes After Expanded Criteria Donor Kidney Transplants

Use of expanded criteria donors (ECD) has increased worldwide in previous years because of the donor scarcity. However, ECD are related to a greater risk of complications and shorter graft longevity. Delayed graft function (DGF) which impacts renal graft survival, represents one of the most common complications posttransplantation. The purpose of this study was to analyse DGF incidence among ECD kidneys and its role on early and intermediate recipient and graft survivals. We prospectively analyzed 46 ECD cases divided as group A (absence of DGF; n = 23) and B (DGF; n = 23). Group B was composed of older donors ( P = .033) with longer cold ischemia times ( P = .017), and greater incidences of acute rejection episodes (ARE) ( P < .0001). Comparing group A with group B, we observed 1-year and 3-year overall recipient survivals to be 95.7% and 95.7% versus 91.3% and 91.3%, respectively ( P = not significant). Censored 1-year and 3-year overall graft survivals were 100% and 92.9% versus 85.6% and 79.9%, respectively ( P = .026). Analyzing the patients with DGF without ( n = 9) versus with concomitant ARE ( n = 14), no differences were noted in recipient and graft survivals. The incidence of DGF was strictly related to increased donor age, greater cold ischemia time, and presence of an ARE while DGF did not have a role in recipient survival, it reduced, graft survival. Concomitant ARE was not related to an impaired graft function.

Association of Lower Costs of Pulsatile Machine Perfusion in Renal Transplantation from Expanded Criteria Donors

Pulsatile machine perfusion (PMP) has been shown to reduce delayed graft function (DGF) in expanded criteria donor (ECD) kidneys. Here, we investigate whether there is a cost benefit associated with PMP utilization in ECD kidney transplants. We analyzed United States Renal Data System (USRDS) data describing Medicare-insured ECD kidney transplant recipients in 1995-2004 (N = 5840). We examined total Medicare payments for transplant hospitalization and annually for 3 years posttransplant according to PMP utilization. After adjusting for other recipient, donor and transplant factors, PMP utilization was associated with a $2130 reduction (p = 0.007) in hospitalization costs. PMP utilization was also associated with lower DGF risk (p < 0.0001). PMP utilization did not predict differences in rejection, graft survival, patient survival, or costs at 1, 2 and 3 years posttransplant. PMP utilization is correlated with lower costs for the transplant hospitalization, which is likely due to the associated reduction in DGF among recipients of PMP kidneys. However, there is no difference in long-term Medicare costs for ECD recipients by PMP utilization. A prospective trial is necessary as it will help determine if the associations seen here are due to PMP utilization and not differences in the population studied.

Sirolimus Use in Recipients of Expanded Criteria Donor Kidneys

With changing donor characteristics and the growing shortage in organ supply, renal transplant practitioners have sought to optimize the use of expanded criteria donor (ECD) kidneys, which have poorer outcomes than standard criteria donor (SCD) kidneys. The outcomes may represent an acceptable trade-off if ECD transplants offer enhanced overall patient survival by reducing waiting times. ECD kidneys may be more susceptible to toxicity associated with calcineurin inhibitors (CNIs); therefore, a potential strategy to improve outcomes in this growing demographic is the use of CNI-free immunosuppressive protocols. To date, published clinical studies have demonstrated encouraging outcomes using sirolimus-based CNI-free regimens in SCD kidney transplant recipients. We conducted a pilot study to examine outcomes in ECD kidney transplant recipients receiving a CNI-free quadruple drug regimen, consisting of antithymocyte globulin (ATG), sirolimus, mycophenolate mofetil (MMF) and a corticosteroid, compared with outcomes in a retrospective CNI-control group of ECD recipients who had received standard CNI-based immunosuppressive treatment. Patient survival and allograft survival at 1 year were not significantly different between the CNI-free group (n = 13) and the CNI-control group (n = 13) [100% vs 92% and 92% vs 85%, respectively]; nor was the incidence of rejection (26% and 31%) or delayed graft function (38% of patients in both groups). Serum creatinine was significantly lower and the estimated glomerular filtration rate was significantly higher for the CNI-free group at 3-6 months but not at 1 year. Protocol biopsies in the CNI-free patients at 1 year revealed no significant progression of chronic vascular lesions. Banff chronic/sclerosing allograft nephropathy scores were 42% grade I, 25% grades II and III, and 33% grade 0. Thus, a sirolimus-based CNI-free regimen may improve outcomes in ECD kidney transplant recipients and merits further study.

Sirolimus‐based triple immunosupression with antithymocyte globulin induction in expanded criteria donor kidney transplantation

Target of rapamycin inhibitors have presented similar graft and patient outcomes with no evidence of drug-induced nephrotoxicity when compared with calcineurin inhibitors. The principal aim of this study is to demonstrate the efficacy of sirolimus-based triple immunosuppression with antithymocyte globulin induction in expanded donor kidney transplantation. Twenty-seven primary expanded criteria donor kidney transplant recipients were recruited. The severity of kidney damage was qualified by zero-hour biopsies. Protocol biopsies were performed at 1 year to assess the chronic allograft damage. Death, graft function, proteinuria and adverse events were systematically analysed during the study period. The mean follow up was 20.2 months. Patient and graft survival was 100% with a mean glomerular filtration rate (GFR) of 53.1+/-4.9 mL/min at last follow up. The cumulative incidence of acute rejection was 11% at the last follow up. At 1 year, mean creatinine, GFR and proteinuria were 1.84 mg/dL, 52.3 mL/min, 651.5 mg/day, respectively. Four patients required surgical intervention due to urinary complications and recovered successfully. Two patients developed acute graft dysfunction due to acute tubular necrosis which was presumably drug related. Ten patients developed relapsing urinary tract infections and three patients had pneumonia. No infectious death occurred throughout the study period. Baseline renal structure was preserved in 13 biopsies at 1 year post transplant. Five patients demonstrated progressive but mild tubular atrophy or interstitial fibrosis in their protocol biopsies. The mean chronic allograft damage index scores at baseline and at 1 year from biopsy were 2.57+/-0.23 and 2.83+/-0.23, respectively (P=0.046). Low-dose sirolimus-based triple immunosuppression with antibody induction offered a safe clinical outcome in expanded criteria donor kidneys with the achievement of stable renal function and favourable recipient outcomes throughout the short term. However, mild progression of histological damage and increased risk of bacterial infection are a major concern. Additionally, the benefit (if any) of the low acute rejection rate on long-term graft outcome is still undetermined.

Pulsatile perfusion is beneficial in expanded criteria donor kidney transplantation

Pulsatile perfusion is beneficial in expanded criteria donor kidney transplantation

Pulsatile Perfusion Reduces the Incidence of Delayed Graft Function in Expanded Criteria Donor Kidney Transplantation

The use of expanded criteria donors (ECD) has been proposed to help combat the discrepancy between organ availability and need. ECD kidneys are associated with delayed graft function (DGF) and worse long-term survival. The aim of this study is to evaluate the impact of pulsatile perfusion (PP) on DGF and graft survival in transplanted ECD kidneys. From January 2000 to December 2003, 4618 ECD kidney-alone transplants were reported to the United Network for Organ Sharing. PP was performed on 912 renal allografts. The prognostic factors of DGF were analyzed using multivariate logistic regression analysis. Risk factors for reduced allograft viability were greater in donors and recipients of PP kidneys. Three-year graft survival of ECD kidneys preserved with PP was similar to cold storage (CS) kidneys. The incidence of DGF in PP kidneys was significantly lower than CS kidneys (26% vs. 36%, p < 0.001). Despite having a greater number of risk factors for reduced graft viability, the ECD-PP kidneys had similar graft survival compared to ECD-CS kidneys. The use of PP, by decreasing the incidence of DGF, may possibly lead to lower overall costs and increased utilization of donor kidneys.

Deceased-Donor Characteristics and the Survival Benefit of Kidney Transplantation

Transplantation using kidneys from deceased donors who meet the expanded criteria donor (ECD) definition (age > or =60 years or 50 to 59 years with at least 2 of the following: history of hypertension, serum creatinine level >1.5 mg/dL [132.6 micromol/L], and cerebrovascular cause of death) is associated with 70% higher risk of graft failure compared with non-ECD transplants. However, if ECD transplants offer improved overall patient survival, inferior graft outcome may represent an acceptable trade-off. To compare mortality after ECD kidney transplantation vs that in a combined standard-therapy group of non-ECD recipients and those still receiving dialysis. Retrospective cohort study using data from a US national registry of mortality and graft outcomes among kidney transplant candidates and recipients. The cohort included 109,127 patients receiving dialysis and added to the kidney waiting list between January 1, 1995, and December 31, 2002, and followed up through July 31, 2004. Long-term (3-year) relative risk of mortality for ECD kidney recipients vs those receiving standard therapy, estimated using time-dependent Cox regression models. By end of follow-up, 7790 ECD kidney transplants were performed. Because of excess ECD recipient mortality in the perioperative period, cumulative survival did not equal that of standard-therapy patients until 3.5 years posttransplantation. Long-term relative mortality risk was 17% lower for ECD recipients (relative risk, 0.83; 95% confidence interval, 0.77-0.90; P<.001). Subgroups with significant ECD survival benefit included patients older than 40 years, both sexes, non-Hispanics, all races, unsensitized patients, and those with diabetes or hypertension. In organ procurement organizations (OPOs) with long median waiting times (>1350 days), ECD recipients had a 27% lower risk of death (relative risk, 0.73; 95% confidence interval, 0.64-0.83; P<.001). In areas with shorter waiting times, only recipients with diabetes demonstrated an ECD survival benefit. ECD kidney transplants should be offered principally to candidates older than 40 years in OPOs with long waiting times. In OPOs with shorter waiting times, in which non-ECD kidney transplant availability is higher, candidates should be counseled that ECD survival benefit is observed only for patients with diabetes.

Expanded Criteria Donors: Process and Outcomes

Expanded criteria donor (ECD) kidneys are transplantable deceased donor (DD) kidneys for which the average patient, graft survival, and renal function are inferior when compared to standard criteria DD kidneys. Although the term ECD kidneys has been used since the early 1990s to describe kidneys with various characteristics associated with poorer outcomes, the concept has been formally implemented in U.S. organ allocation. A DD kidney is considered to be an ECD organ if the estimated adjusted risk of graft failure is > or = 70% (RR > or = 1.70) compared to DD kidneys with standard characteristics of transplant suitability. The donor characteristics that define an ECD kidney include age > or = 60 years, or age 50-59 years plus two of the following: cerebrovascular accident as the cause of death, preexisting hypertension, or terminal serum creatinine greater than 1.5 mg/dl. In the aggregate, recipients of ECD kidneys have improved survival compared to end-stage renal disease (ESRD) patients on the kidney transplant waiting list. Patient survival is 5% lower at 1 year and 8-12% lower at 3-5 years for ECD kidney recipients. Adjusted graft survival in ECD kidneys is 8% lower at 1 year and 15-20% lower at 3-5 years after transplantation compared to standard criteria donor kidneys. However, patients less than 40 years of age, African Americans, Asians for whom the median waiting time is less than 1350 days receive no survival benefit from ECD kidney transplantation. Informed choice by the potential recipient is a prominent feature of the allocation policy regarding ECD kidneys. Since there are recipient characteristics associated with no survival benefit following ECD transplantation, nephrologists who refer patients for kidney transplantation should be familiar with the combination of donor and recipient factors that are likely to yield detrimental results.

Expanded Criteria Donors for Kidney Transplantation

The shortage of deceased donor kidneys for transplantation continues to restrict the full application of this lifesaving procedure to all who might benefit. Increasing reliance on donors with characteristics previously thought to be unsuitable for use in transplantation has led to questions about graft outcomes for recipients of such organs. Careful definition of the expanded criteria donor (ECD) for kidney has facilitated modifications of national organ allocation policy that are designed to increase procurement, improve use, decrease cold ischemia time, and lead to improved outcome. The effects of these policy changes in the United States have been studied recently and are reviewed here. In addition, the impact of ECD kidney transplantation on mortality risk among candidates awaiting deceased donor renal transplantation is examined. Further studies of ECD organs and their recipients are needed to optimize the use of these scarce resources.

Impact of the Expanded Criteria Donor Allocation System on the Use of Expanded Criteria Donor Kidneys

The U.S. Organ Procurement and Transplantation Network recently implemented a policy allocating expanded criteria donor (ECD) kidneys by waiting time alone. ECD kidneys were defined as having a risk of graft failure > or = 1.7 times that of ideal donors. ECDs include any donor > or = 60 years old and donors 50 to 59 years old with at least two of the following: terminal creatinine >1.5 mg/dL, history of hypertension, or death by cerebrovascular accident. The impact of this policy on use of ECD kidneys is assessed. The authors compared use of ECD kidneys recovered in the 18 months immediately before and after policy implementation. Differences were tested using t test and chi2 analyses. There was an 18.3% increase in ECD kidney recoveries and a 15.0% increase in ECD kidney transplants in the first 18 months after policy implementation. ECD kidneys made up 22.1% of all recovered kidneys and 16.8% of all transplants, compared with 18.8% (P<0.001) and 14.5% (P<0.001), respectively, in the prior period. The discard rate was unchanged. The median relative risk (RR) for graft failure for transplanted ECD kidneys was 2.07 versus 1.99 in the prepolicy period (P=not significant); the median RR for procured ECD kidneys was unchanged at 2.16. The percentage of transplanted ECD kidneys with cold ischemia times (CIT) <12 hr increased significantly; the corresponding percentage for CIT > or = 24 hr decreased significantly. The recent increase in ECD kidney recoveries and transplants appears to be related to implementation of the ECD allocation system.

FIRST YEAR IMPACT OF THE NEW U.S. EXPANDED CRITERIA DONOR (ECD) KIDNEY ALLOCATION SYSTEM ON THE RECOVERY AND UTILIZATION OF ECD KIDNEYS

O327* Aims: On 10/31/02, the United States Organ Procurement and Transplantation Network (OPTN) implemented a national policy that allocates expanded criteria donor (ECD) kidneys by waiting time alone. ECD kidneys were defined in previous studies as having a risk of graft failure that is 1.7 times greater than that of a reference population of nonhypertensive deceased-donors between the ages of 10 and 39 years, whose cause of death was not from cerebral vascular accident (CVA), and whose terminal creatinine was ≤1.5 mg/dl. ECDs include any donor >age 60 years and donors 50-59 years with any two of a terminal creatinine >1.5 mg/dl, a history of hypertension, or death by CVA. We assessed the impact of this innovation on the recovery and utilization of ECD kidneys. Methods: Using the Scientific Registry of Transplant Recipients (SRTR)/OPTN database, we compared the use of ECD kidneys recovered between 11/02 and 10/03 with kidneys meeting ECD criteria that were procured during a similar time period (11/01 through 10/02) in the year prior to ECD policy implementation. Differences were tested using t-test and Chi-square analyses. Results: Between 11/02 and 10/03, there was a 14.8% increase in ECD kidney recoveries and a 10.7% increase in ECD kidney transplants compared with the prior year. ECD kidneys made up 21.2% of all recovered kidneys and 16.0% of all transplants performed, compared with 18.9% (p<0.0001) and 14.6% (p=0.011), respectively, in the prior time period. The median relative risk for graft failure (based on ECD risk factors) for transplanted ECD kidneys increased from 1.99 to 2.16, while the median relative risk for procured ECD kidneys was unchanged at 2.16. ECD donors were >60 years old in 55.5% of cases. Conclusions: An increase in the number of kidney recoveries and transplants from ECD donors was observed under the newly introduced ECD allocation system. The use of pulsatile perfusion and the fraction of ECD kidneys with cold ischemia periods of less than 12 hours have increased significantly. Early analysis of ECD kidney utilization under this allocation policy supports its contination.Figure