Standard Criteria Donor Kidneys Research Articles

Impact of donor expanded criteria kidney transplantation on clinical outcomes and survival: A single-center experience

IntroductionThe scarcity of suitable donor organs has led to the inclusion of Expanded Criteria Donor (ECD) kidneys to augment the donor pool, despite potential concerns regarding post-transplant outcomes. MethodsThis retrospective study analyzed the clinical outcomes of a cohort of 317 kidney transplant recipients from deceased donors at a single center between 2008 and 2018. Patients were categorized into ECD and Standard Criteria Donor (SCD) groups, with primary nonfunctioning grafts excluded. Comprehensive laboratory evaluations were conducted, including HLA typing and serum creatinine levels. Immunosuppressive regimens were standardized, and statistical analyses were performed using the SPSS program. ResultsThe sample consisted of 83 (26.18%) patients who received kidney transplants from ECDs and 234 (73.82%) from SCDs. The ECD group showed a longer cold ischemia time (p = 0.019) and a higher rate of delayed graft function (DGF) compared with the SCD group. No significant differences were observed in graft survival (p = 0.370) or patient survival (p = 0.993) between the ECD and SCD groups. However, differences in graft survival were noted between the groups when stratified by DGF status: ECD with DGF vs. ECD without DGF (p = 0.029), ECD with DGF vs. SCD with DGF (p = 0.188), ECD with DGF vs. SCD without DGF (p = 0.022), ECD without DGF vs. SCD with DGF (p = 0.014), ECD without DGF vs. SCD without DGF (p = 0.340), and SCD with DGF vs. SCD without DGF (p = 0.195). No differences in patient survival rates were observed among these groups for all pairwise comparisons (p > 0.05) when stratified by donor criteria and DGF status. ConclusionsGraft and patient survival rates were comparable between ECD and SCD kidney transplant recipients.

A tale of two kidneys, and the case for machine perfusion in South Africa.

Extended-criteria donors (ECDs) are seen as a means of addressing the shortfall in solid-organ availability for transplant. However, the use of ECD kidneys is associated with a greater risk of primary non-function compared with standard-criteria donor kidneys, and a higher discard rate has been described internationally. There seems to be a lack of consensus in the consideration of ECD kidneys for transplant, with reliance often placed on the subjective assessment of individual clinicians. The following case examines the difference in the institutional decision-making process applied to two kidneys from a single donor, and provides an argument for the use of hypothermic machine perfusion in low- to middle-income countries as an efficacious and objective means of assessing ECD kidney suitability.

Survival Advantage Comparing Older Living Donor Versus Standard Criteria Donor Kidney Transplants.

The aim of this analysis was to explore mortality outcomes for kidney transplant candidates receiving older living donor kidneys (age ≥60years) versus younger deceased donors or remaining on dialysis. From 2000 to 2019, all patients on dialysis listed for their first kidney-alone transplant were included in a retrospective cohort analysis of UK transplant registry data. The primary outcome was all-cause mortality, with survival analysis conducted by intention-to-treat principle. Time-to-death from listing was modelled using nonproportional hazard Cox regression models with transplantation handled as a time-dependent covariate. A total of 32,978 waitlisted kidney failure patients formed the primary study cohort, of whom 18,796 (58.5%) received a kidney transplant (1,557 older living donor kidneys and 18,062 standard criteria donor kidneys). Older living donor kidney transplantation constituted only 17.0% of all living donor kidney transplant activity (overall cohort; n = 9,140). Recipients of older living donor kidneys had reduced all-cause mortality compared to receiving SCD kidneys (HR 0.904, 95% CI 0.845-0.967, p = 0.003) and much lower all-cause mortality versus remaining on the waiting list (HR 0.160, 95% CI 0.149-0.172, p < 0.001). Older living kidney donors should be actively explored to expand the living donor kidney pool and are an excellent treatment option for waitlisted kidney transplant candidates.

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.

All Expanded Criteria Donor Kidneys are Equal But are Some More Equal Than Others? A Population-Cohort Analysis of UK Transplant Registry Data.

Survival outcomes for kidney transplant candidates based on expanded criteria donor (ECD) kidney type is unknown. A retrospective cohort study was undertaken of prospectively collected registry data of all waitlisted kidney failure patients receiving dialysis in the United Kingdom. All patients listed for their first kidney-alone transplant between 2000-2019 were included. Treatment types included; living donor; standard criteria donor (SCD); ECD60 (deceased donor aged ≥60years); ECD50-59 (deceased donor aged 50-59years with two from the following three; hypertension; raised creatinine and/or death from stroke) or remains on dialysis. The primary outcome was all-cause mortality, with time-to-death from listing analyzed using time-dependent non-proportional Cox regression models. The study cohort comprised 47,917 waitlisted kidney failure patients, of whom 34,558 (72.1%) received kidney transplantation. ECD kidneys (n = 7,356) were stratified as ECD60 (n = 7,009) or ECD50-59 (n = 347). Compared to SCD, both ECD60 (Hazard Ratio 1.126, 95% CI 1.093-1.161) and ECD50-59 (Hazard Ratio 1.228, 95% CI 1.113-1.356) kidney recipients have higher all-cause mortality. However, compared to dialysis, both ECD60 (Hazard Ratio 0.194, 95% CI 0.187-0.201) and ECD50-59 (Hazard Ratio 0.218, 95% CI 0.197-0.241) kidney recipients have lower all-cause mortality. ECD kidneys, regardless of definition, provide equivalent and superior survival benefits in comparison to remaining waitlisted.

Survival after kidney transplantation compared with ongoing dialysis for people over 70 years of age: A matched-pair analysis

Kidney transplantation offers improved survival and quality of life compared to dialysis for most recipients; however, benefits for elderly patients (>70 years) remain uncertain. Using the Australia and New Zealand Dialysis and Transplant Registry (2009-2019), elderly transplant recipients were matched to a waitlisted dialysis patient by age, cause of end-stage kidney disease, and dialysis duration (paired controls). We censored dialysis patients at the time of transplant. Survival was compared using stratified Cox regression. Elderly transplant recipients (KTRs) (n = 465) were matched to waitlisted pairs. Transplant group mortality initially exceeded dialysis due to excess infection-related deaths (1.9 transplant versus 0.3 dialysis/100 patient-years, P = .03). Beyond month 9, a progressive survival benefit in favor of transplantation was apparent. Over a median follow-up of 1.7 years, mortality was 38% lower for KTRs (95% confidence interval 0.41-0.94, P = .02), and 5-year survival was 80% KTRs vs 53% dialysis (P < .001). Recipients of living and standard criteria donor kidneys acquired immediate survival advantage compared with dialysis, while recipients of expanded criteria donor's kidneys experienced elevated risk of death for the first 17 months. Compared with remaining on dialysis, elderly KTRs incur an increased risk of early posttransplant mortality but thereafter may anticipate progressively superior survival rates.

Long-term outcomes of kidney transplantation from deceased donors with terminal acute kidney injury: Single center experience and literature review.

Long-term outcomes of kidney transplantation from deceased donors (DDKTs) with terminal acute kidney injury (AKI) are not well defined. Single center retrospective review of DDKTs from 1/31/07-12/31/19. AKI kidneys were defined by a doubling of the donor's admission serum creatinine (SCr) level AND a terminal SCr ≥2.0mg/dl. A total of 188 AKI DDKTs were performed, including 154 from brain-dead standard criteria donors (SCD). Mean donor age was 36 years and mean Kidney Donor Profile Index was 50%; mean admission and terminal SCr levels were 1.3 and 3.1mg/dl, respectively. With a mean follow-up of 94 months (median 89 months), overall patient (both 71.3%) and graft survival (54% AKI vs. 57% non-AKI) rates were comparable to concurrent DDKTs from brain-dead non-AKI SCDs (n=769). Delayed graft function (DGF) was higher in AKI kidney recipients (47%vs. 20% non-AKI DDKTs, p<.0001). DGF was associated with lower graft survival in recipients of both AKI and non-AKI SCD kidneys but the impact was earlier and more pronounced in non-AKI recipients. Despite having more than twice the incidence of DGF, kidneys from deceased donors with terminal AKI have long-term outcomes comparable to non-AKI SCD kidneys and represent a safe and effective method to expand the donor pool.

Distinct global DNA methylation and NF-κB expression profile of preimplantation biopsies from ideal and non-ideal kidneys.

Epigenetic mechanisms may affect the ideal and non-ideal kidneys selected for transplantationand their inflammatory gene expression profile differently and may contribute to poor clinical outcomes. Study the Global DNA methylation and the expression profiles of the DNA methyltransferases (DNMTs) and nuclear factor kappa B (NF-κB) in preimplantation kidney biopsies from ideal and non-ideal kidneys (expanded criteria donor (ECD) and with KDPI > 85%). In a sample consistingof45 consecutive pre-implantation biopsies,global DNA methylation levels were detected by LINE-1 repeated elements using bisulfite pyrosequencing. DNMT gene expression was assessed by real-time quantitative polymerase chain reaction, and NF-κB protein expression by immunofluorescence. ECD kidneys displayed increased methylation levels in LINE-1, and DNMT1 and DNMT3B expression was upregulated when comparing ECD to standard criteria donor kidneys. Similarly, kidneys with KDPI > 85% exhibited increased LINE-1 methylation and DNMT1 upregulation when compared to a KDPI ≤ 85%. NF-κB protein expression levels were greatly increased in both types of non-ideal kidneys compared to ideal kidneys. Moreover, hypermethylation of LINE-1 was associated with cold ischemia time > 20h and ECD kidney classification. This study shows that global DNA hypermethylation and high expression of NF-κB occurred in both types of non-ideal kidneys and were associated with prolonged cold ischemia time. Global DNA methylation can be a useful tool to assess non-ideal kidneys and hence, could be used to expand the pool of kidneys donors.

P2.11: Distinct Global DNA Methylation and NF-κB Expression Profile of Preimplantation Biopsies From Ideal and Non-ideal Kidneys

Background: Epigenetic mechanisms may differently affect the ideal and non-ideal kidneys and their inflammatory gene expression profile and may contribute to poor clinical outcomes. Objective: To identify the Global DNA methylation was evaluated, as well as the expression profiles of the DNA methyltransferases (DNMTs) and nuclear factor kappa B (NF-κB) in preimplantation kidney biopsies from ideal and non-ideal kidneys (extended criteria donor-ECD and with KDPI>85%). Methods: Global DNA methylation was estimated by LINE-1 repeated elements methylation using bisulfite pyrosequencing, DNMTs expression was assessed by q-PCR and NF-κB protein expression by immunofluorescence. Results: ECD kidneys displayed increased methylation levels in LINE-1, and DNMT1 and DNMT3B expression were upregulated when comparing ECD to standard criteria donor kidneys. Similarly, kidneys with KDPI > 85% exhibited increased LINE-1 hypermethylation and DNMT1 upregulation vs. kidneys with a KDPI ≤ 85%. NF-κB protein expression levels were greatly increased in both types of non-ideal kidneys compared to ideal kidneys. Moreover, hypermethylation of LINE-1 was associated with cold ischemia time > 20 h and ECD kidney classification. Conclusions: This study shows that global DNA hypermethylation and high expression of NF-κB occurred in both types of non-ideal kidneys and were associated with prolonged cold ischemia time. Global DNA methylation can be a useful tool to assess suboptimal kidneys and hence, could be used to increase the use of these kidneys to expand the donor pool. This study was supported by São Paulo State Research Foundation (FAPESP – Fundação de Amparo à Pesquisa do Estado de São Paulo) grant number 2016/08301-8.

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.

Analysis of the acceptance practice of deceased donor kidneys in a single Hungarian transplant centre

Kidney transplantation in Hungary is carried out via Eurotransplant (ET). Our centre in Debrecen receives around 200 kidney offers a year, of which 37% are accepted. Not all accepted kidneys are transplanted, which can be a result of a number of causes. Obejctive: A debreceni szakmai gyakorlat elemzése és bemutatása reprezentatív mintán. Between November 2016 and March 2020, the centre of Debrecen received 624 kidney offers. 37% (n=229) of the offered kidneys got preliminarily accepted, of which 63% (n = 144) were transplanted later. In our centre, standard criteria donor kidneys were accepted and transplanted in significantly higher rate, than extended criteria donor kidneys. Looking at accepted and rejected kidneys, KDPI and KDRI values were significantly higher in the case of the refused ones (p<0.001). Part of our assessment is to analyze whether kidneys offered to and refused by us got accepted in other transplant centres. In the examined period, of the 624 kidneys offered to our centre 144 were transplanted in Debrecen, 313 were transplanted in other ET centres, while 167 were not transplanted at all (discarded organ). The majority of transplanted kidneys in other ET centres had KDPI values between 36 and 85 (180 kidneys.) KDPI and KDRI values of kidneys transplanted in our centre were significantly lower than those that were offered to us, but got transplanted elsewhere. To summarize, we can say that high-risk donor organs are refused in the transplant centre of Debrecen, while the majority of them are being transplanted in other centres. Based on this, kidneys of KDPI value between 36 and 85 are a possible source of expanding the number of transplantations, with regards to the recipient. Orv Hetil. 2021; 162(26): 1022-1028.

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.

Multicenter registry analysis comparing survival on home hemodialysis and kidney transplant recipients in Australia and New Zealand.

In the era of organ shortage, home hemodialysis (HHD) has been identified as the possible preferential bridge to kidney transplantation. Data are conflicting regarding the comparability of HHD and transplantation outcomes. This study aimed to compare patient and treatment survival between HHD patients and kidney transplant recipients. The Australia and New Zealand Dialysis and Transplant Registry was used to include incident HHD patients on Day 90 after initiation of kidney replacement therapy and first kidney-only transplant recipients in Australia and New Zealand from 1997 to 2017. Survival times were analyzed using the Kaplan-Meier product-limit method comparing HHD patients with subtypes of kidney transplant recipients using the log-rank test. Adjusted analyses were performed with multivariable Cox proportional hazards regression models for time to all-cause mortality. Time-to-treatment failure or death was assessed as a composite secondary outcome. The study compared 1411 HHD patients with 4960 living donor (LD) recipients, 6019 standard criteria donor (SCD) recipients and 2427 expanded criteria donor (ECD) recipients. While LD and SCD recipients had reduced risks of mortality compared with HHD patients [LD adjusted hazard ratio (HR) = 0.57, 95% confidence interval (CI) 0.46-0.71; SCD HR = 0.65 95% CI 0.52-0.79], the risk of mortality was comparable between ECD recipients and HHD patients (HR = 0.90, 95% CI 0.73-1.12). LD, SCD and ECD kidney recipients each experienced superior time-to-treatment failure or death compared with HHD patients. This large registry study showed that kidney transplant offers a survival benefit compared with HHD but that this advantage is not significant for ECD recipients.

P1431MULTI-CENTER REGISTRY ANALYSIS COMPARING SURVIVAL ON HOME HEMODIALYSIS AND KIDNEY TRANSPLANT RECIPIENTS IN AUSTRALIA AND NEW ZEALAND

Abstract Background and Aims In the era of organ shortage, home hemodialysis (HHD) has been identified as the possible preferential bridge to kidney transplantation. Data are conflicting regarding the comparability of HHD and transplantation outcomes. This study aimed to compare patient and treatment survival between HHD patients and kidney transplant recipients. Method The Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry was used to include incident HHD patients on day 90 after initiation of kidney replacement therapy and first kidney-only transplant recipients in Australia and New Zealand from 1997 to 2017. Survival times were analyzed using the Kaplan-Meier product limit method comparing HHD patients to subtypes of kidney transplant recipients using the log-rank test. Adjusted analyses were performed with multivariable Cox proportional hazards regression models for time to all-cause mortality. Time-to-treatment failure or death was assessed as a composite secondary outcome. Results The study compared 1411 HHD patients to 4960 living donor (LD) recipients, 6019 standard criteria donor (SCD) recipients and 2427 expanded criteria donor (ECD) recipients. While LD and SCD recipients had reduced risks of mortality compared to HHD patients (LD adjusted hazard ratio [HR] 0.57, 95%CI 0.46-0.71; SCD HR 0.65 95%CI 0.52-0.79), the risk of mortality was comparable between ECD recipients and HHD patients (HR 0.90, 95%CI 0.73-1.12). LD, SCD and ECD kidney recipients each experienced superior time-to-treatment failure or death compared to HHD patients. Conclusion This large registry study showed that kidney transplant offers a survival benefit compared to HHD but that this advantage is not significant for ECD recipients.

Effectiveness of serum beta-2 microglobulin as a tool for evaluating donor kidney status for transplantation

Kidney transplantations using expanded criteria donors (ECD) are being increasingly adopted, but no consensus tools are available to evaluate donor kidney status. Beta-2 microglobulin (B2MG) is a marker of kidney function, and herein, we evaluate the usefulness of assessing B2MG to evaluate donor kidney status. Fifty-seven kidney transplantations were performed from March 2017 to April 2019. Medical records were retrospectively reviewed, and relationships between clinical and laboratory variables and transplant outcomes were investigated. Thirty-eight patients received a standard criteria donor kidney and 19 patients an ECD kidney. Ten patients experienced delayed graft function (DGF), but no patient experienced primary nonfunction. Of the parameters studied, only donor renal replacement therapy (RRT) [odds ratio (OR) 24.162; p = 0.018] and donor serum B2MG (OR 22.685; p = 0.022) significantly predicted DGF. The presence of either of these two risk factors can better reflect the condition of the donor than previous classification. However, on their last follow-up creatinine and estimated glomerular filtration rate values in those with or without these risk factors were not significantly different. For an ECD with a B2MG level of <7.18 and no history of RRT, kidney transplantation can be undertaken without considering the possibility of kidney discard.

Delayed graft function is correlated with graft loss in recipients of expanded-criteria rather than standard-criteria donor kidneys: a retrospective, multicenter, observation cohort study.

Background:Although the use of expanded-criteria donors (ECDs) alleviates the problem of organ shortage, it significantly increases the incidence of delayed graft function (DGF). DGF is a common complication after kidney transplantation; however, the effect of DGF on graft loss is uncertain based on the published literature. Hence, the aim of this study was to determine the relationship between DGF and allograft survival.Methods:We conducted a retrospective, multicenter, observation cohort study. A total of 284 deceased donors and 541 recipients between February 2012 and March 2017 were included. We used logistic regression analysis to verify the association between clinical parameters and DGF, and Cox proportional hazards models were applied to quantify the hazard ratios of DGF for kidney graft loss.Results:Among the 284 deceased donors, 65 (22.8%) donors were ECD. Of the 541 recipients, 107 (19.8%) recipients developed DGF, and this rate was higher with ECD kidneys than with standard-criteria donor (SCD) kidneys (29.2% vs. 17.1%; P = 0.003). The 5-year graft survival rate was not significantly different between SCD kidney recipients with and without DGF (95.8% vs. 95.4%; P = 0.580). However, there was a significant difference between ECD kidney recipients with and without DGF (71.4% vs. 97.6%; P = 0.001), and the adjusted hazard ratio (HR) for graft loss for recipients with DGF was 1.885 (95% confidence interval [CI] = 1.305–7.630; P = 0.024). Results showed that induction therapy with anti-thymocyte globulin was protective against DGF (odds ratio = 0.359; 95% CI = 0.197–0.652; P = 0.001) with all donor kidneys and a protective factor for graft survival (HR = 0.308; 95% CI = 0.130–0.728; P = 0.007) with ECD kidneys.Conclusion:DGF is an independent risk factor for graft survival in recipients with ECD kidneys, but not SCD kidneys.

Utilization of Standard Criteria Donor and Expanded Criteria Donor Kidneys After Kidney Allocation System Implementation.

BackgroundImplementation of the Kidney Allocation System (KAS) changed how kidneys are allocated and the information on which organ utilization decisions are based. We aimed to evaluate how KAS implementation changed kidney utilization and recipient outcomes.Material/MethodsUsing the United Network for Organ Sharing database, we identified recipients of kidney transplants from donors with kidney donor profile index (KDPI) of 61–90% in the 5-years pre- and 18-months post-KAS implementation and examined patient and graft survival and donor kidney discard rates based on standard criteria donor (SCD) or expanded criteria donor (ECD) status.ResultsThe proportion of ECD kidneys was unchanged pre- versus post-KAS. Post-KAS, SCD kidneys were less likely to be transplanted into young recipients while ECD kidneys were more likely to be transplanted. SCD kidneys in the post-KAS period conferred a 1.42 (95% CI: 1.18–1.73) times higher adjusted mortality and 2% lower 1-year survival (94.2% vs. 96.2%, P<0.001) but had unchanged graft failure compared to pre-KAS. For ECD kidneys, there was no difference in mortality or graft survival. The discard rate increased after KAS for both SCD and ECD kidneys (P<0.05) but was not different between SCD and ECD kidneys for any KDPI group.ConclusionsAfter KAS implementation, patient survival for recipients of SCD kidneys was significantly worse.

Preimplantation Kidney Biopsies of Extended Criteria Donors Have a Heavier Inflammatory Burden Than Kidneys From Standard Criteria Donors.

BackgroundDonors after brain death develop a systemic proinflammatory state that may predispose the kidneys to injury after transplantation. Because it is not known whether this inflammatory environment similarly affects the kidneys from expanded criteria donor (ECD) and standard criteria donors (SCD), we sought to evaluate differences in the gene expression of inflammatory cytokines in preimplantation biopsies (PIBx) from ECD and SCD kidneys.MethodsCytokines gene expression was measured in 80 PIBx (SCD, 52; ECD, 28) and associated with donor variables.ResultsNormal histology and chronic histological lesions were not different between both types of kidneys. ECD kidneys showed significant increase in the transcripts of MCP-1, RANTES, TGF-β1, and IL-10 when compared with SCD. Kidneys presenting normal histology had similar inflammatory profile except by a higher expression of RANTES observed in ECD (P = 0.04). Interstitial fibrosis and tubular atrophy (interstitial fibrosis and tubular atrophy ≥ 1) were associated with higher expression of TGF-β1, RANTES, and IL-10 in ECD compared with SCD kidneys. Cold ischemia time of 24 hours or longer was significantly associated with upregulation of FOXP3, MCP-1, RANTES, and IL10, whereas longer duration of donor hospitalization significantly increased gene expression of all markers. High FOXP3 expression was also associated with lower level of serum creatinine at 1 year. Donor age was not associated with any of the transcripts studied.ConclusionsPIBx of ECD exhibit a higher gene expression of inflammatory cytokines when compared with SCD kidneys. This molecular profile may be a specific ECD kidney response to brain death and may help to predict the posttransplant outcomes of ECD recipients.

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.