Expanded Criteria Donor Kidney Transplantation Research Articles

Impact of Donation After Circulatory Death on Outcomes of Expanded Criteria Donor Kidney Transplants

Expanded criteria donor (ECD) kidneys experience suboptimal outcomes compared with standard criteria donor kidneys. To examine the additional impact of deceased organ category, donation after circulatory death (DCD), and neurologic determination of death (NDD) on ECD outcomes, we examined 1- and 3-year patient and graft survival in all ECD kidney recipients in our institution between January 2008 and December 2017. Of 166 ECD recipients, 49 (29.5%) were DCD and 117 (70.5%) were NDD. Delayed graft function was higher in the DCD/ECD group 61.2 % vs 32.0 % among NDD/ECD recipients. Graft loss was significantly increased among DCD/ECD (hazard ratio for graft loss 4.81 [95% CI1.78-13.01], P = .002 at 1 year and 2.03 [95% CI 1.03-4.0], P = .042 at 3 years). Death-censored graft loss was higher among DCD/ECD (hazard ratio was 10.12 [95% CI, 2.14, 47.92], P = .004 at 1 year and 2.83 [95% CI, 1.24, 6.46], P = .014 at 3 years). There was no statistically significant difference in all-cause mortality. Our study demonstrated that DCD/ECD kidneys have lower graft survival compared with NDD/ECD kidneys. Time on dialysis, waiting time, and panel reactive antibody should be taken into account when offering these organs to patients.

Early Graft Loss Following Transplantation From Expanded Criteria Donors.

Expanded criteria donor (ECD) kidneys are associated with higher graft loss rates than standard criteria donor kidneys. We sought to determine factors associated with early graft loss and their discrimination ability for this outcome compared with kidney donor risk index. Data were extracted from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) for ECD transplants between 1997 and 2014. The primary outcome was early graft loss (all-cause graft loss within 3 y of transplantation). Death-censored graft loss was substituted as a sensitivity analysis. Era-adjusted odds ratios were calculated by multivariable logistic regression for donor, recipient, and transplant factors available at transplantation. Discrimination was assessed by c-statistic, with 95% confidence intervals (CIs) calculated by bootstrapping. Of 2152 ECD kidney transplants, early graft loss occurred in 406 (19%) and was associated with recipient diabetes, smoking, First Nations recipients, and oliguria. Of factors defining ECD (age, elevated terminal creatinine, hypertension, death from cerebrovascular accident), all but mode of death were associated with early graft loss. The multivariable model, including known donor, recipient, and transplant factors, was moderately good at predicting early graft loss (c-statistic 0.65; 95% CI, 0.62-0.68). Recipient factors (c-statistic 0.62; 95% CI, 0.59-0.65) performed equally well compared with donor factors (c-statistic 0.60; 95% CI, 0.57-0.64) or the kidney donor risk index (c-statistic 0.60; 95% CI, 0.56-0.63). Early graft loss occurs in approximately one-fifth of ECD kidney transplants. The discriminatory value of commonly used recipient, donor, and transplant factors are approximately comparable and limited.

Oxygenated End-Hypothermic Machine Perfusion in Expanded Criteria Donor Kidney Transplant

Continuous hypothermic machine perfusion during organ preservation has a beneficial effect on graft function and survival in kidney transplant when compared with static cold storage (SCS). To compare the effect of short-term oxygenated hypothermic machine perfusion preservation (end-HMPo2) after SCS vs SCS alone on 1-year graft survival in expanded criteria donor kidneys from donors who are brain dead. In a prospective, randomized, multicenter trial, kidneys from expanded criteria donors were randomized to either SCS alone or SCS followed by end-HMPo2 prior to implantation with a minimum machine perfusion time of 120 minutes. Kidneys were randomized between January 2015 and May 2018, and analysis began May 2019. Analysis was intention to treat. On randomization and before implantation, deceased donor kidneys were either kept on SCS or placed on HMPo2. Primary end point was 1-year graft survival, with delayed graft function, primary nonfunction, acute rejection, estimated glomerular filtration rate, and patient survival as secondary end points. Centers in 5 European countries randomized 305 kidneys (median [range] donor age, 64 [50-84] years), of which 262 kidneys (127 [48.5%] in the end-HMPo2 group vs 135 [51.5%] in the SCS group) were successfully transplanted. Median (range) cold ischemia time was 13.2 (5.1-28.7) hours in the end-HMPo2 group and 12.9 (4-29.2) hours in the SCS group; median (range) duration in the end-HMPo2 group was 4.7 (0.8-17.1) hours. One-year graft survival was 92.1% (n = 117) in the end-HMPo2 group vs 93.3% (n = 126) in the SCS group (95% CI, -7.5 to 5.1; P = .71). The secondary end point analysis showed no significant between-group differences for delayed graft function, primary nonfunction, estimated glomerular filtration rate, and acute rejection. Reconditioning of expanded criteria donor kidneys from donors who are brain dead using end-HMPo2 after SCS does not improve graft survival or function compared with SCS alone. This study is underpowered owing to the high overall graft survival rate, limiting interpretation. isrctn.org Identifier: ISRCTN63852508.

Impact of pre-transplant biopsy on 5-year outcomes of expanded criteria donor kidney transplantation.

Compared to Standard Criteria Donors (SCD), Expanded Criteria Donor (ECD) kidneys are associated with poorer outcomes, although pre-transplant biopsy may mitigate risks. This study assessed 5-year outcomes of deceased-donor kidney transplant recipients, comparing recipients of ECD allografts evaluated histologically to recipients of SCD and ECD kidneys assessed clinically. This is a single-centre retrospective study. From November 2005 to December 2009 (Era 1), donors were assessed clinically for suitability for kidney donation. From December 2009 to October 2017 (Era 2), kidneys from ECDs and diabetics underwent pre-transplant biopsy and were allocated based on Remuzzi score. Outcomes of Era 1 and 2 recipients were compared. ECD kidney transplantation increased from 30.4% to 40.0% from Era 1 to 2. Univariable Cox regression, stratified by transplant era, found that 5-year graft loss was highest with Era 1 ECD (HR 2.5, 95% CI 1.1-5.5, P = .027) while graft loss for Era 2 ECD recipients was similar to SCD recipients. There was no difference in 5-year recipient survival. Amongst Era 1 ECD recipients, 51.2% experienced rejection compared to 30.8-41.5% for other subgroups. Five-year eGFR was higher with Era 2 ECD at 48.4 (33.3-60.7) ml/min/1.73 m2 compared to 42.2 (35.8-57.3) ml/min/1.73 m2 for Era 1 ECD. However, these differences were not statistically significant. Introduction of pre-transplant biopsy assessment may be associated with improved outcomes of ECD kidney recipients such that they are now comparable to SCD kidney recipients, with benefits persisting over 5 years.

P1725USAGE AND OUTCOMES FOR EXPANDED CRITERIA DONOR KIDNEY TRANSPLANTATION IN THE KOREA CHARACTERIZED BY KIDNEY DONOR PROFILE INDEX, SINGLE CENTER STUDY

Abstract Background and Aims The demand for Kidney transplantation (KT) is increasing and the number of patients who are waiting for KT is steadily increasing. Therefore, there is an increasing prevalence of KT done by cadaver donor especially, expanded criteria donor. We used Kidney Donor Profile Index (KDPI) to predict the renal prognosis of expanded criteria donor (ECD) KT recipient. Method We investigated patients undergo KT by ECD from March 2013 to June 2018 respectively. Through the donor’s last creatinine level, KDPI score, and Kidney Donor Risk Index (KDRI) score the renal survival rate was compared with ROC curve analysis. Results The mean age of a total 59 ECD KT recipient is 53.85 ± 9.9 years old. Mean follow up duration after KT was 35.0 ± 18.5 months. 10 patients had KDPI score above 85 (KDPI ≥ 85). Five cases undergo dialysis after KT. Nine cases expired during follow up (four sepsis, three sudden cardiac arrest, one hyperkalemia). Glomerular filtration rate one year after KT was significantly associated with KDPI (r=-0.772, p<0.001). The area under curve (AUC) of KDPI was 0.700 (95% CI 0.494-0.906) and cut off point was 75.5. All renal survival patients had KDPI score below 75.5 Conclusion Our results show that KDPI could be used as an indicator for predicting the prognosis of the Korean ECD KT.

Predicting Clinical Outcome in Expanded Criteria Donor Kidney Transplantation: A Retrospective Cohort Study.

Background:The gaps in organ supply and demand necessitate the use of expanded criteria donor (ECD) kidneys.Objective:To identify which pre-transplant and post-transplant predictors are most informative regarding short- and long-term ECD transplant outcomes.Design:Retrospective cohort study.Setting:Single center, Quebec, Canada.Patients:The patients were 163 consecutive first-time ECD kidney only transplant recipients who underwent transplantation at McGill University Health Centre (MUHC) between January 1, 2008 and December 31, 2014 and had frozen section wedge procurement biopsies.Measurements:Short-term graft outcomes, including delayed graft function and 1-year estimated glomerular filtration rate (eGFR), as well as long-term outcomes including all-cause graft loss (defined as return to dialysis, retransplantation, and death with function).Methods:Pre-transplant donor, recipient, and transplant characteristics were assessed as predictors of transplant outcomes. The added value of post-transplant predictors, including longitudinal eGFR, was also assessed using time-varying Cox proportional hazards models.Results:In univariate analyses, among the pre-transplant donor characteristics, histopathologic variables did not show evidence of association with delayed graft function, 1-year post-transplant eGFR or all cause graft loss. Recipient age was associated with all-cause graft loss (hazard ratio: 1.038 [95% confidence interval: 1.002-1.075] and the model produced only modest discrimination (C-index: 0.590; standard error [SE]: 0.045). Inclusion of time-dependent post-transplant eGFR improved the model’s prediction accuracy (C-index: 0.711; SE = 0.047). Pre-transplant ECD characteristics were not associated with long-term survival, whereas post-transplant characteristics allowed better model discrimination.Limitations:Single-center study, small sample size, and potential incomplete capture of all covariate data.Conclusions:Incorporation of dynamic prediction models into electronic health records may enable timely mitigation of ECD graft failure risk and/or facilitate planning for renal replacement therapies. Histopathologic findings on preimplantation biopsies have a limited role in predicting long-term ECD outcomes.Trial registration:Not applicable.

232.6: Outcomes of dual kidney transplantation: Comparison to single kidney transplantation from standard and expanded criteria donors.

Background: Nowadays, kidney transplantation (KT) is accepted as the treatment of choice for patients with end-stage renal disease (ESRD). However, due to a severe donor shortage, many ESRD patients are still on the waiting list and are suffering from the disease, even though use of kidney from expanded criteria donor (ECD) is increasing. Dual kidney transplantation (DKT) can be the way to use more kidneys from ECDs. We are trying to compare the outcomes of Dual kidney transplantation with those of single kidney transplantation from standard criteria donors (SCDs) and ECDs. Methods: In 2014, we started dual kidney transplantation using kidneys from donors of over 70 years with one of the risk factor including serum creatinine (sCr) level is over 3.0 mg/dl, or estimated glomerulus filtration rate (eGFR) is under 30 ml/min. By 2017, we performed 15 cases of DKT. We compared the outcomes of these 15 recipients with 124 patients who got kidney transplant from SCDs and 80 patients who got kidney transplant from ECDs. Results: Donors of DKT were older, more diabetic, and had higher sCr levels than ECDs and SCDs. Recipients of DKT was also older and diabetic than recipients of ECD and SCDs. Recipients of DKT showed less slow graft function(SGF) and lower nadir sCr than recipients of ECDs. Time to nadir sCr was shorter in DKT than in ECD KT. Graft survival rates and patient survival rates were not significantly different among three groups. Risk factor analysis for graft failure revealed that donor group was not the risk but recipient age and nadir sCr. Conclusions: The graft survival rates of DKT were compatible with those of ECD KT and SCD KT. Some outcomes such as the incidence of SGF, nadir sCr level, and time to nadir sCr were even more favorable in DKT than in ECD KT. Therefore, DKT should be considered as an option to expand donor pool.

Prospective randomized study comparing everolimus and mycophenolate sodium in de novo kidney transplant recipients from expanded criteria deceased donor.

The optimal immunosuppressive regimen for recipients of expanded criteria donor (ECD) kidneys has not been identified. In this single-center study, 171 recipients of ECD kidney transplants were randomized to receive antithymocyte globulin induction, and delayed introduction of reduced dose tacrolimus, prednisone and everolimus (r-ATG/EVR, n=88), or mycophenolate (r-ATG/MPS, n=83). No cytomegalovirus (CMV) pharmacological prophylaxis was used. The primary endpoint was the incidence of CMV infection/disease at 12months. Secondary endpoints included treatment failure [first biopsy-proven acute rejection (BPAR), graft loss, or death] and safety. Patients treated with EVR showed a 89% risk reduction (13.6 vs. 71.6%; HR 0.11, 95% CI 0.06-0.220, P<0.001) in the incidence of first CMV infection/disease. Incidences of BPAR (16% vs. 5%, P=0.021), graft loss (11% vs. 1%, P=0.008), death (10% vs. 1%, P=0.013), and treatment discontinuation (40% vs. 28%, P=0.12) were higher in the r-ATG/EVR, leading to premature study termination. Mean glomerular filtration rate was lower in r-ATG/EVR (31.8±18.8 vs. 42.6±14.9, P<0.001). In recipients of ECD kidney transplants receiving no CMV pharmacological prophylaxis, the use of everolimus was associated with higher treatment failure compared with mycophenolate despite the significant reduction in the incidence of CMV infection/disease (ClinicalTrials.gov.NCT01895049).

A Retrospective Cohort Study on Rehospitalization following Expanded Criteria Donor Kidney Transplantation.

Background Expanded criteria donor (ECD) kidneys are commonly used but are associated with increased graft failure. Graft failure is in turn related to rehospitalization within thirty days post transplant. Our goal was to determine whether ECD kidneys independently lead to rehospitalization within 30 days, 1 year, and 2 years after transplant. Methods All adult first-time recipients of deceased donor kidneys transplanted from 2003–2012 at our center were reviewed. Models included demographics, medical comorbidities, center for disease control high-risk kidney, ECD kidney, ischemia times, cause of renal failure, immunosuppressive regimen, positive psychiatric screening, alcoholism, surgeon, year the transplant was performed, years on dialysis before transplant, and the number of inpatient hospitalizations within 6 months prior to transplant. We conducted Andersen–Gill modeling and propensity score matching followed by logistic regression. We also used multivariable linear regression to predict average length of stay during rehospitalization. Results More ECD patients had a rehospitalization at 1 year (70.3% versus 59%, log-rank test p=0.014). Thirty-day and 2-year time marks were not significant. Andersen–Gill models predicting successive hospitalizations yielded HR of 1.42 (p=0.002) and 1.32 (p=0.015) for ECD patients at 1 and 2 years of after transplantation, respectively. Propensity score matching and logistic regression showed a significant relative risk of 1.630 at one year (p=0.033) and 1.313 at two years (p=0.268). There was no significant association between ECD and subsequent lengths of hospital stay. Conclusion Receiving an ECD kidney is independently associated with multiple readmissions within 2 years of transplant but unrelated to length of stay.

Lymphocyte depletion and risk of acute rejection in renal transplant recipients at increased risk for delayed graft function.

Delayed graft function (DGF) is a risk factor for acute rejection (AR) in renal transplant recipients, and KDIGO guidelines suggest use of lymphocyte-depletion induction when DGF is anticipated. We analyzed the United Network for Organ Sharing/Organ Procurement and Transplantation Network (UNOS/OPTN) database to assess the impact of induction immunosuppression on the risk of AR in deceased kidney recipients based on pretransplant risk of DGF using a validated model. Recipients were categorized into 4 groups based upon the induction immunosuppression: (1) Rabbit anti-thymocyte globulin (rATG); (2) Alemtuzumab (C1H); (3) IL2-receptor antagonists (IL2-RA; basiliximab or daclizumab), and (4) No antibody induction. The primary endpoint for analysis was a composite endpoint of treated AR or graft failure by 1-year posttransplantation. Compared to no antibody induction, rATG and C1H had consistently lower adjusted odds of the composite endpoint across all risk strata for DGF risk, whereas IL2-Ra was associated with increased adjusted odds of the composite endpoint with increasing DGF risk. When the induction agents were compared, rATG and C1H were associated with decreasing adjusted odds for the composite endpoint with increasing risk of DGF, especially at the higher risk spectrum of DGF. Consideration must be given to use of lymphocyte-depletion induction when the anticipated risk of DGF is increased.

Early Immunosuppressive Exposure of Enteric-Coated-Mycophenolate Sodium Plus Tacrolimus Associated with Acute Rejection in Expanded Criteria Donor Kidney Transplantation.

Background:Immunosuppressive agents are still inefficient in preventing biopsy-proven acute rejection (BPAR) after expanded criteria donor (ECD) kidney transplantation. The aim of this study was to investigate the relationships between early immunosuppressive exposure and the development of BPAR.Methods:We performed a retrospective study of 58 recipients of ECD kidney transplantation treated with enteric-coated-mycophenolate sodium, tacrolimus (Tac), and prednisone. The levels of mycophenolic acid-area under the curve (MPA-AUC)0-12h and Tac C0 were measured at the 1st week and the 1st month posttransplant, respectively. The correlation was assessed by multivariate logistic regression.Results:The occurrence rates of BPAR and antibody-mediated rejection were 24.1% and 10.3%, respectively. A low level of MPA-AUC0-12h at the 1st week posttransplant was found in BPAR recipients (38.42 ± 8.37 vs. 50.64 ± 13.22, P < 0.01). In addition, the incidence of BPAR was significantly high (P < 0.05) when the MPA-AUC0-12h level was <30 mg·h-1·L-1 at the 1st week (15.0% vs. 44.4%) or the Tac C0 was <4 ng/ml at the 1st month posttransplant (33.3% vs. 21.6%). Multivariable logistic regression analysis showed that the MPA-AUC0-12h at the 1st week (OR: 0.842, 95% CI: 0.784-0.903) and the Tac C0 at the 1st month (OR: 0.904, 95% CI: 0.822–0.986) had significant inverse correlation with BPAR (P < 0.05).Conclusions:Low-level exposure of MPA and Tac C0 in the early weeks posttransplant reflects an increased acute rejection risk, which suggested that MPA-AUC0-12h <30 mg·h-1·L-1 and Tac C0 <4 ng/ml should be avoided in the first few weeks after transplantation.

Liver Transplant Recipients With End-Stage Renal Disease Largely Benefit From Kidney Transplantation

BackgroundThe incidence of end-stage renal disease (ESRD) after liver transplant (LT) has increased. The actual benefit of kidney transplantation (KT) is not completely understood in LT recipients with ESRD. MethodsWe analyzed Scientific Registry of Transplant Recipients data for all KT candidates with prior LT from 1998 to 2014; the benefits of KT relative to remaining on dialysis were compared by means of multivariate Cox proportional hazards regression analysis. ResultsThe number of these KT candidates with prior LT has tripled from 98 in 1998 to 323 in 2015; LT recipients with ESRD remaining on dialysis have a 2.5-times increase in the risk of liver graft failure and a 3.6-times increase in the risk of patient death compared with these patients receiving KT. The adjusted liver graft and patient survival rates after donors from donation after cardiac death or expanded-criteria donor kidney transplantation were significantly higher than in patients remaining on dialysis in LT recipients with ESRD. ConclusionsThe number of referrals to KT with prior LT is increasing at a rapid rate. Remaining on dialysis in LT recipients with ESRD has profound increased risks of liver graft failure and patient death in comparison to receiving a KT. LT recipients with ESRD can benefit from expanded-criteria donor and donation after cardiac death kidney transplantation.

Increased risk of graft failure and mortality in Dutch recipients receiving an expanded criteria donor kidney transplant

Survival of expanded criteria donor (ECD) kidneys and their recipients has not been thoroughly evaluated in Europe. Therefore, we compared the outcome of ECD and non-ECD kidney transplantations in a Dutch cohort, stratifying by age and diabetes. In all first Dutch kidney transplants in recipients ≥18years between 1995 and 2005, both relative risks (hazard ratios, HR) and adjusted absolute risk differences (RD) for ECD kidney transplantation were analysed. In 3062 transplantations [recipient age 49.0 (12.8)years; 20% ECD], ECD kidney transplantation was associated with graft failure including death [HR 1.62 (1.44-1.82)]. The adjusted HR was lower in recipients ≥60years of age [1.32 (1.07-1.63)] than in recipients 40-59years [1.71 (1.44-2.02) P=0.12 for comparison with ≥60years] and recipients 18-39years [1.92 (1.42-2.62) P=0.03 for comparison with ≥60years]. RDs showed a similar pattern. In diabetics, the risks for graft failure and death were higher than in the nondiabetics. ECD kidney grafts have a poorer prognosis than non-ECD grafts, especially in younger recipients (<60years), and diabetic recipients. Further studies and ethical discussions should reveal whether ECD kidneys should preferentially be allocated to specific subgroups, such as elderly and nondiabetic individuals.

Trends in Usage and Outcomes for Expanded Criteria Donor Kidney Transplantation in the United States Characterized by Kidney Donor Profile Index.

There has been increasing concern in the kidney transplant community about the declining use of expanded criteria donors (ECD) despite improvement in survival and quality of life. The recent introduction of the Kidney Donor Profile Index (KDPI), which provides a more granular characterization of donor quality, was expected to increase utilization of marginal kidneys and decrease the discard rates. However, trends and practice patterns of ECD kidney utilization on a national level based on donor organ quality as per KDPI are not well known. We, therefore, performed a trend analysis of all ECD recipients in the United Network for Organ Sharing (UNOS) registry between 2002 and 2012, after calculating the corresponding KDPI, to enable understanding the trends of usage and outcomes based on the KDPI characterization. High-risk recipient characteristics (diabetes, body mass index ≥30 kg/m2, hypertension, and age ≥60 years) increased over the period of the study (trend test p<0.001 for all). The proportion of ECD transplants increased from 18% in 2003 to a peak of 20.4% in 2008 and then declined thereafter to 17.3% in 2012. Using the KDPI >85% definition, the proportion increased from 9.4% in 2003 to a peak of 12.1% in 2008 and declined to 9.7% in 2012. Overall, although this represents a significant utilization of kidneys with KDPI >85% over time (p<0.001), recent years have seen a decline in usage, probably related to regulations imposed by Centers for Medicare & Medicaid Services (CMS).When comparing the hazards of graft failure by KDPI, ECD kidneys with KDPI >85% have a slightly lower risk of graft failure compared to standard criteria donor (SCD) kidneys with KDPI >85%, with a hazard ratio (HR) of 0.95, a confidence interval (CI) of 0.94-0.96, and statistical significance of p<0.001. This indicates that some SCD kidneys may actually have a lower estimated quality, with a higher Kidney Donor Risk Index (KDRI), than some ECDs. The incidence of delayed graft function (DGF) in ECD recipients has significantly decreased over time from 35.2% in 2003 to 29.6% in 2011 (p=0.007), probably related to better understanding of the donor risk profile along with increased use of hypothermic machine perfusion and pretransplant biopsy to aid in optimal allograft selection.The recent decline in transplantation of KDPI >85% kidneys probably reflects risk-averse transplant center behavior. Whether discard of discordant SCD kidneys with KDPI >85% has contributed to this decline remains to be studied.

Outcomes of kidney transplants and risk of infection transmission from increased infectious risk donors.

Concern over transmission of viral infections has been reported to result in higher discard rates of high infectious risk kidneys (HIR) although data on actual viral transmission rates are lacking. At our center, we performed 89 HIR and 533 non-HIR kidney transplants (KTs) between 2004 and 2011. Follow-up screening labs in recipients of HIR kidneys tested for human immunodeficiency virus, hepatitis C virus, and hepatitis B virus did not reveal any cases of viral transmission over median follow-up of 4.3years. Patient and graft outcomes were similar at 5years between HIR and non-HIR KTs. An updated analysis of the Organ Procurement and Transplant Network (OPTN) registry of deceased-donor kidney transplants between 2008 and 2012 included 57526 transplants was performed. Retrospective calculation of KDRI (kidney donor risk index) differed (P<.001) between all groups with median KDRI of 0.99 for HIR kidneys, 1.07 for non-HIR standard criteria donor kidneys, and 1.81 for non-HIR expanded criteria donor (ECD) kidneys. This was reflected in the significantly improved 5-year graft survival for HIR KTs when compared with non-HIR ECD KTs (84% vs 78%; P<.001). Our data can guide counseling of KT candidates about the safety and benefits of HIR kidneys.

Comparison of survival outcomes between Expanded Criteria Donor and Standard Criteria Donor kidney transplant recipients: a systematic review and meta-analysis

In 2002, the United Network for Organ Sharing proposed increasing the pool of donor kidneys to include Expanded Criteria Donor (ECD). Outside the USA, the ECD definition remains the one used without questioning whether such a graft allocation criterion is valid worldwide. We performed a meta-analysis to quantify the differences between ECD and Standard Criteria Donor (SCD) transplants. We paid particular attention to select studies in which the methodology was appropriate and we took into consideration the geographical area. Thirty-two publications were included. Only five studies, all from the USA, reported confounder-adjusted hazard ratios comparing the survival outcomes between ECD and SCD kidney transplant recipients. These five studies confirmed that ECD recipients seemed to have poorer prognosis. From 29 studies reporting appropriate survival curves, we estimated the 5-year pooled nonadjusted survivals for ECD and SCD recipients. The relative differences between the two groups were lower in Europe than in North America, particularly for death-censored graft failure. It is of primary importance to propose appropriate studies for external validation of the ECD criteria in non-US kidney transplant recipients.

Renal transplantation with expanded criteria donors: Which is the optimal immunosuppression?

The growing gap between demand and supply for kidney transplants has led to renewed interest in the use of expanded criteria donor (ECD) kidneys in an effort to increase the donor pool. Although most studies of ECD kidney transplantation confirm lower allograft survival rates and, generally, worse outcomes than standard criteria donor kidneys, recipients of ECD kidneys generally have improved survival compared with wait-listed dialysis patients, thus encouraging the pursuit of this type of kidney transplantation. The relative benefits of transplantation using kidneys from ECDs are dependent on patient characteristics and the waiting time on dialysis. Because of the increased risk of poor graft function, calcineurin inhibitor (CNI)-induced nephrotoxicity, increased incidence of infections, cardiovascular risk, and malignancies, elderly recipients of an ECD kidney transplant are a special population that requires a tailored immunosuppressive regimen. Recipients of ECD kidneys often are excluded from transplant trials and, therefore, the optimal induction and maintenance immunosuppressive regimen for them is not known. Approaches are largely center specific and based upon expert opinion. Some data suggest that antithymocyte globulin might be the preferred induction agent for elderly recipients of ECD kidneys. Maintenance regimens that spare CNIs have been advocated, especially for older recipients of ECD kidneys. CNI-free regimens are not universally accepted due to occasionally high rejection rates. However, reduced CNI exposure and CNI-free regimens based on mammalian target of rapamycin inhibitors have shown acceptable outcomes in appropriately selected ECD transplant recipients.

Impact of Early Low-Grade Proteinuria and Allograft Dysfunction on Survival in Expanded Criteria Donor Kidney Transplant Recipients

IntroductionRecent studies have demonstrated a relationship between low-grade proteinuria and worse graft survival, but this has not been fully studied in expanded criteria donor (ECD) kidney transplant recipients. AimThe aim of this study was to assess whether the combination of early low-grade proteinuria (<1 g/d) and allograft dysfunction at the third month post-transplantation predicts outcomes in terms of survival in ECD kidney transplant recipients. Material and MethodsWe studied a cohort of 269 ECD kidney transplant recipients subdivided into 4 groups according to clinically relevant proteinuria (300 mg/d) and median creatinine (Cr; 1.7 mg/dL; interquartile range, 1.4–2.1 mg/dL) at the third month post-transplantation: Group A (Cr <1.7 mg/dL and proteinuria <300 mg/24 h; n = 97), Group B (Cr <1.7 mg/dL and proteinuria ≥300 mg/24 h; n = 38), Group C (Cr ≥1.7 mg/dL and proteinuria <300 mg/24 h; n = 79), and Group D (Cr ≥1.7 mg/dL and proteinuria ≥300 mg/24 h; n = 55). ResultsDeath-censored graft survival was significantly lower in Group D compared with the rest (P < .007). Multivariate Cox regression analysis using fixed covariates showed that the combination of low-grade proteinuria and a lower estimated glomerular filtration rate (eGFR) as associated with graft failure (hazard rate [HR] 2.5, 95% confidence interval [CI], 1.09–5.97; P = .03). ConclusionsThe early association of low-grade proteinuria and allograft dysfunction represents an important risk factor for graft loss in ECD kidney transplant recipients. Strategies to optimize renal function could improve the outcome in this specific population.

Machine Perfusion: Initial Results in an Expanded Criteria Donor Kidney Transplant Program

BackgroundDelayed graft function (DGF) negatively impacts graft survival. Expanded criteria donors (ECD) show a higher rate of DGF. Hypothermic machine perfusion (HMP) has shown a DGF decrease and an increase of survival at 1 year. Several authors found that renal resistance (RR) at the end of machine perfusion was an independent risk factor for the development of DGF and poorer graft survival. The objective of this study was to analyze HMP results in the context of an ECD program and assess the impact of donor parameters and resistance index (RI) during perfusion in graft survival after kidney transplantation. MethodsDonor age, terminal creatinine, machine perfusion time, percentage of glomerulosclerosis, and RI at the end of the perfusion were considered as risk predictors. Univariate and multivariate Cox regression analysis was constructed to find independent risk factors of DGF. Finally, diagnostic validity for RR was determined by sensitivity, specificity, and positive and negative predictive values. ResultsTwenty-three percent of patients developed DGF. We found no difference in the ability of flow or RI to predict the development of DGF. The predictive accuracy of RI for DGF by receiver operator characteristic curve was poor, with a c-statistic of 0.66 (95% CI, 0.50–0.81; P = .046). Our analysis did not identify risk factors that predicted graft survival at 1 year. Patient and graft survival were 98.8% and 89.7%, respectively. ConclusionsHMP has reduced the rate of DGF in our cohort of recipients of ECD grafts compared with historical data (23.3% vs 38.0%). Analysis did not identify risk pretransplant factors for graft survival at 1 year.

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.