ECD Kidneys Research Articles

Different Patterns of Foxp3 Gene Expression in Pre-and Post-Transplantation Kidney Biopsies and the Effect of Use Mammalian Target of Rapamycin Inhibitors

Trafficking of regulatory T cells (Tregs) modulates the inflammatory response after kidney transplantation (KTx). There is scarce information on whether circulating and intragraft Tregs are similarly affected by immunosuppressive drugs and the type of deceased kidney donor. FOXP3 gene expression was measured in the pretransplant kidney biopsies (PIBx) from donors who met extended (ECD) and standard (SCD) criteria donors. In the third month after KTx, the patients were divided according to tacrolimus (Tac) or everolimus (Eve) and the type of kidney they had received. FOXP3 gene expression in the peripheral blood (PB) and kidney biopsies (Bx) was analyzed using real-time polymerase chain reaction. FOXP3 gene expression in the PIBx was higher in ECD kidneys. FOXP3 gene expression in the PB and Bx was greater in Eve- than in Tac-treated patients. However, SCD recipients treated with Eve (SCD/Eve) had higher FOXP3 expression than ECD/Eve. Pretransplant kidney biopsies from ECD kidneys had higher FOXP3 gene expression than SCD, and the use of Eve may affect the expression of the FOXP3 gene only in SCD kidneys.

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.

Non-Adherence to Appointments is a Strong Predictor of Medication Non-Adherence and Outcomes in Kidney Transplant Recipients

BackgroundNon-adherence is an important aspect of transplantation that affect outcomes. This study aims to investigate the impact of non-adherence to laboratory and clinic appointments on medication non-adherence and outcomes in kidney transplant (KT) recipients. MethodsWe analyzed KT recipients between 2005-14 with a detailed review of the medical records for non-adherence to laboratory and clinic appointments, as well as medication regimens. Baseline characteristics and clinical outcomes were compared between adherent and non-adherent groups. ResultsA total of 1413 KT recipients were included: 754 who were adherent and 659 who were non-adherent. Non-adherent recipients tend to be younger, African American, and have private insurance. Adherent patients tend to have a history of DM, heart disease, and receive an ECD kidney. Non-adherence to appointments was a strong predictor of medication non-adherence (OR 3.1), acute rejection (OR 1.4), and subsequent rejection episodes (OR 3.3 and 8.1 respectively for ≥ 1 and ≥ 2 rejection episodes). Subset analysis of patients who had early non-adherence within 1-year post-transplant showed predominance of younger, African American patients. The same patients had higher prevalence of medication non-compliance, overall and ≥ 1-year post-transplant, and mean number of readmissions. Kaplan-Meier analysis showed a trend towards lower graft survival in this group. ConclusionsEarly non-adherence to laboratory and clinic appointments is a strong predictor of late medication non-adherence, acute rejection, and graft loss. Targeting patients that demonstrate early non-adherence to appointments with focused interventions may help improve kidney transplant outcomes in this high risk group.

P1688THE IMPACT OF KIDNEY DONOR PROFILE INDEX (KDPI) AND KIDNEY DONOR RISK INDEX (KDRI) ON KIDNEY TRANSPLANT FUNCTION: A MONOCENTRIC ANALYSIS AFTER ONE YEAR OF FOLLOW UP

Abstract Background and Aims Evaluation of kidney donors is a complex process based on the elaboration of clinical, laboratory and imaging data. Until 2014, the quality of kidney transplant (KTx) was assessed considering standard donation criteria (SCD) or extended donation criteria (ECD). ECD kidneys (kECD) defined subjects older than 65 years without comorbidities or younger, but with comorbidities, such as hypertension, cerebral stroke, high creatinine level (above 1.5 mg/dL). The Kidney Donor Risk Index (KDRI) is an estimate of the relative risk of post-transplant kidney graft failure from a particular deceased donor compared to a reference donor. The value obtained is than converted in a percentage called KDPI (KDPI ≥85% is considered as similar of a kidney from ECD), which represent the percentage of utilized donor in the last year better than the considered. Italian experience in Donor Cardiac Death (DCD) is growing and doubled last KTx year, reaching 1.1 pmp in 2018, with the 22.5% of donors procured at our center. Our DCD KTx protocol has been active since November 2017, with promising results. We considered only controlled DCD (cDCD) Maastricht Class III. Methods We compared all DCD and DBD KTx performed in the Nephrology Unit of the University Hospital of Modena, Italy, from November 2017 to December 2018. We excluded living donor transplantation and combined liver–kidney transplantation. In this study, only cDCD are considered. We studied KDPI and KDRI score for both DBD and DCD KTx . Comparison between data from DCD and DBD was performed with t – Student and Chi Square test, survival analysis according to Kaplan-Meier and a Pearson correlation between KPI-KDRI and one year graft function was elaborated. ROC curve analysis was performed for KDPI – KDRI and DGF for both groups. A p lower than 0.05 was considered significant. Results A total of 28 DBD KTx, 18 double (64.3%) and 10 single (35.7%) and 7 DCD KTx, 3 double (42.8%) and 4 single (57.2%) were observed during the study. Donors and recipients clinical and immunological characteristics are reported in table1. All of DCD and 64.3% of DBD donors underwent kidney biopsy (Karpinski values are reported in table 1). Induction therapy was with aTG in DCD KTx and ECD DBD KTx and with anti-interleukin-2 receptor monoclonal antibodies in SCD DBD KTx. Maintenance immunosuppression consisted in steroid, tacrolimus and mycophenolic acid. KTx outcomes were reported in table 1 with no differences in both groups between creatinine (p0.3) and eGFR (p0.25). We analyzed KDPI and KDRI values from DBD and DCD KTx and we stratified them as reported in table 2. We found 7 DGF in DBD KTx (85% with KDPI >85% and KDRI >1.5) and only 1 DGF in DCD KTx with KDPI>85% and KDRI > 1.5. We did not find a statistical correlation between KDPI- KDRI and eGFR in both DBD KTx (2 patients died and 3 patients were lost at follow up) (r -0.32, p 0.13; r -0.26, p 0.22) and DCD KTx (r -0.59, p 0.15; r -0.47, p 0.28). (Figure 1) We performed a ROC curve Analysis to investigate the role of KDPI – KDRI and the risk of DGF. We found no statistical correlation in DCD KTx, considering the small sample size (p 0.61) but we found a significant statistical value in DBD KTx (p 0.03 – p 0.02 with a AUC of 0.77-0.78). Survival analysis did not show statistical difference between DBD and DCD (p 0.72), no graft loss in the first year, although two DBD (92.8%) recipients died (1circulatory arrest,1 sepsis), no one died in DCD group. Conclusion cDCD is a valid resource for KTx, with similar outcomes to DBD. This remarks the importance of a multidisciplinary team and a correct selection of donors. We did not find a correlation between KDPI-KDRI and KTX function after one year of follow up in our population for either group.

Hypothermic Oxygenated Perfusion Versus Static Cold Storage for Expanded Criteria Donors in Liver and Kidney Transplantation: Protocol for a Single-Center Randomized Controlled Trial.

BackgroundExtended criteria donors (ECD) are widely utilized due to organ shortage, but they may increase the risk of graft dysfunction and poorer outcomes. Hypothermic oxygenated perfusion (HOPE) is a recent organ preservation strategy for marginal kidney and liver grafts, allowing a redirect from anaerobic metabolism to aerobic metabolism under hypothermic conditions and protecting grafts from oxidative species–related damage. These mechanisms may improve graft function and survival.ObjectiveWith this study, we will evaluate the benefit of end-ischemic HOPE on ECD grafts for livers and kidneys as compared to static cold storage (SCS). The aim of the study is to demonstrate the ability of HOPE to improve graft function and postoperative outcomes of ECD kidney and liver recipients.MethodsThis is an open-label, single-center randomized clinical trial with the aim of comparing HOPE with SCS in ECD kidney and liver transplantation. In the study protocol, which has been approved by the ethics committee, 220 patients (110 liver recipients and 110 kidney recipients) will be enrolled. Livers and kidneys assigned to the HOPE group undergo machine perfusion with cold Belzer solution (4-10°C) and continuous oxygenation (partial pressure of oxygen of 500-600 mm Hg). In the control group, livers and kidneys undergoing SCS are steeped in Celsior solution and stored on ice. Using the same perfusion machine for both liver and kidney grafts, organs are perfused from the start of the back-table procedure until implantation, without increasing the cold ischemia time. For each group, we will evaluate clinical outcomes, graft function tests, histologic findings, perfusate, and the number of allocated organs. Publication of the results is expected to begin in 2021.ResultsDynamic preservation methods for organs from high-risk donors should improve graft dysfunction after transplantation. To date, we have recruited 108 participants. The study is ongoing, and recruitment of participants will continue until January 2020.ConclusionsThe proposed preservation method should improve ECD graft function and consequently the postoperative patient outcomes.Trial RegistrationClinicalTrials.gov NCT03837197; https://clinicaltrials.gov/ct2/show/NCT03837197 ; Archived by WebCite® at http://www.webcitation.org/76fSutT3RInternational Registered Report Identifier (IRRID)DERR1-10.2196/13922

Altered Expression of Inflammation Genes in Preimplantation Kidney Biopsies of Extended Criteria Donors

Background Changes to an organ can occur at the time of brain death and a series of inflammatory proteins are generated within the organ. It is not known whether this inflammatory similarly affects the kidneys from extended (ECD) and standard (SCD) criteria donors and because we have previously reported that preimplantation kidney biopsies from ECD donors have a heavier inflammatory profile when compared with SCD donors. In the present study we extended our results using great number of genes and seeking to identify some immunologic pathways involved in the mechanism of sterile inflammation. Methods Pretransplant kidney biopsies (Bx) were obtained from ECD (n=40) and SCD (n=40). Gene expression profile measured by Real Time qPCR Array representing expression levels of genes indicative of inflammation (IL-10, IL-1b, TNF-α, MCP-1, NFK-b, TLR-4, HMGB1, IFN-gamma, TGF-b, Myd-88), cytoprotection (HO-1, HIF-1a), apoptose (CASP-1) and intercellular adhesion (ICAM-1) and correlated with donor variables. Results ECD donors were older had more cerebrovascular accident, arterial hypertension and diabetes (p<0.01) and recipients of ECD kidneys had renal function and 24h proteinuria worst 1 year after transplantation (p<0.006). Genes IL-10, IL-1 β, TLR-4, HMGB-1, HIF-1 and CASP-1 were significantly more expressed in biopsies from ECD than SCD. Presence of DGF, acute rejection, was not associated with any individual transcript. Conclusions The present results confirm and expand our previous findings that ECD kidney is highly inflamed when compared with SCD and that a Myd-88 independent pathway of innate immunity may be activated. We appreciate the FAPESP (#2014/25831-5) for the financial support.

Deceased Kidney Distribution and Allocation in the Kingdom of Saudi Arabia

Background The Saudi Center for Organ Transplantation (SCOT) is the sole supervising, regulating and coordinating body for organ donation and transplantation inside the Kingdom of Saudi Arabia. It is also the referral center for Gulf Cooperation Council (GCC) Countries and adopted the uniform law on regulation on organ sharing among GCC countries as guidelines. In deceased organ donation, kidneys from deceased donors is the most utilized organ in the kingdom, helping patients suffering from ESRD and improving their quality of life by means of kidney transplantation; Thus, we studied the distribution and allocation of these kidneys from the zonal distribution system to kidney allocation and its utilization. Methods & Materials A retrospective review was done during the period of 2014‐2016, using the Critical Pathway of Organ Donation comprising the potential, eligible, actual and utilized deceased kidneys inside the kingdom of Saudi Arabia. Results In 2014 to 2016 a total of 1,160 Potential Deceased Donors (DD) were recorded by SCOT, of which 944(81%) donor’s next of kin were approached for organ donation after declaration of death, and 313 (33%) had given their consent to donate the organs. A total of 626 kidneys were consented, of these 400 (65%) kidneys were transplanted (utilized) in KSA, 106 (17%) kidneys was also utilized by GCC countries including 2 kidneys shared by KSA to UAE, non-recovered kidneys were 96 (15%), while 24 (4%) kidneys were not utilized. In 400 kidneys transplanted in KSA, kidney donors were categorized using the Standard and Extended Criteria (SCD, ECD) and the Donors Kidney Donor Risk Index (KDRI). A total of 290 (72%) SCD kidneys and 110 (28%) ECD kidneys were transplanted while the kidneys transplanted from deceased donors with KRDI index of less than <0.8 were 17 (4%) kidneys, 0.8-1.15, 163 (41%), 1.15-1.45, 113 (28%) and >1.45, 107 (27%) with mean KDRI of 1.25. SCOT allocation protocol allotted 20% of SCD deceased kidneys to Pediatric recipients; in which, 70 kidneys were transplanted; wherein, 69 (99%) SCD kidneys including, 15 kidneys for urgent pediatric was transplanted, and 1 (1%) kidney from ECD donor. Kidneys transplanted for urgent recipient was implemented by SCOT through zonal distribution which amounted to 28 kidneys transplanted mainly due to loss of vascular access. The cold ischemia time (CIT) Ranges from 2 hrs – 34 hrs. with mean CIT of 12 hrs. Discarded kidneys inside the kingdom were 22 kidneys with most reasons are due to kidney related disease. Non-recovered kidneys 96, were mostly due to donor’s sudden cardiac arrest 52 (54%), followed by causes due to medical reasons 38 (40%) and technical reasons 6 (6%).Conclusion Kidney allocation and distribution is a vital role performed by SCOT. It assures, fair distribution of deceased kidneys to transplant centers based on recipient priority criteria and zonal distribution system following the Guidelines in the Directory of Regulations of Organ Transplantation. The SCOT constantly and closely monitor the kidney allocation for pediatric and patients on urgent waiting list were always given the priority. ECD kidneys were also used optimally by offering it to transplant centers thus, increasing the kidneys being utilized.

MicroRNA-21 (miR-21) expression in hypothermic machine perfusate may be predictive of early outcomes in kidney transplantation.

Hypothermic machine perfusion is effective in improving outcome following kidney transplantation. Molecular analyses of hypothermic machine perfusate (HMP) have the potential to identify biomarkers of organ viability prior to transplantation, offering significant advantages to the transplant surgeon, and leading to a potential increase in the organ donor pool. MicroRNAs are emerging as important biomarkers in the context of kidney injury and transplantation. Recent data demonstrate increased microRNA-21 (miR-21) expression in the kidney following acute kidney injury. This study investigated the potential of miR-21 detected in HMP to act as a sentinel for early kidney transplant outcomes. MiR-21 was found to be readily detectable in HMP by RT-qPCR. Eleven ECD kidneys were maintained on a hypothermic machine perfusion system for a median 627 (range 117-1027) minutes, and evaluation of flow and resistance characteristics suggested stability on the machine from 60 min post-perfusion. MiR-21 quantification at 60 min post-perfusion correlated with eGFR at 6 and 12 months post-transplantation. These data suggest that miR-21 expression in HMP may be predictive of early outcomes following kidney transplantation. In the era of ECD kidneys, a reliable measure of organ quality is urgently needed, and this study suggests miR-21 may be such a marker.

Long term outcomes of transplantation using kidneys from expanded criteria donors: prospective, population based cohort study

Objectives To assess the long term outcomes of transplantation using expanded criteria donors (ECD; donors aged ≥60 years or aged 50-59 years with vascular comorbidities) and assess the main determinants...

Evolution of Renal Transplant Practice Over the Past Decade: A U.K. Center Experience

ObjectiveAs renal transplantation continues to evolve, there appears to be a change in both donor and recipient populations. Traditional markers of high-risk donor (e.g. donation after cardiac death [DCD]/expanded criteria donor [ECD]) and recipient (e.g. obese, highly sensitized) operations appear to be more common without any noticeable worsening of patient outcome. The present study aimed to compare outcome and define the change in donor and recipient populations for cadaveric transplants over a 10-year period at a large U.K. center. MethodsSingle-center analysis of all adult patients undergoing cadaveric renal transplantation between January 2004 and January 2014 (n = 754). Transplants were divided into 3 groups (early, middle, and late) depending on the era, with donor, recipient and outcomes compared. ResultsThere were considerable changes in both donor and recipient factors between the 3 eras, with a greater proportion of high-risk operations performed, as reflected by significant increases in Donor Risk Index (median: 1.11–1.16, P = .022), and the proportions of ECD (22.2%–33.9%, P = .003) and DCD kidneys (10.8%–19.4% P = .011). However, 1-year graft survival was comparable between the eras, with a decrease in the average 1-year serum creatinine between the early and late cohort (median: 161 μmol/L vs 132 μmol/L, P < .001). There was no significant increase in body mass index (BMI) in either the donor or recipient population across the eras. ConclusionImprovement in transplant outcome continues despite a greater proportion of transplants previously considered as high risk being performed. This is likely to reflect a considerable improvement in pre- and postoperative management. BMI remains a major continuing block to transplantation.

ECD in Retransplantation UNOS Update:Proceed With Caution.

Introduction: Retransplant is preferred therapy for selected patients with allograft failure. Whether using ECD kidneys for retransplantation is clinically and programmatically prudent is elusive. We explored the last two decades of UNOS database to elucidate outcomes of ECD kidneys in patients with previous graft loss. Methods: Retrospective analysis of 44,296 patients with ECD kidney as their first transplant (Prim-ECD = 25508) and SCD/ECD kidney after previous graft loss (re-SCD =17130; re-ECD = 1658) was done. Cox proportional regression models were fitted to compute hazard ratios and multivariate analysis was done adjusting for age, gender, race, BMI, PRA, HLA mismatch levels, cold ischemia time (CIT), waiting time, region and year of transplantation.Results: Prim-ECD recipients were significantly older than re-ECD and re-SCD recipients (Mean= 58 vs. 49 vs. 42 years, p < .001), more likely to be diabetic (41.5% vs. 23.4% vs. 17.6%; p < .001), frequently obese (30% vs. 21.5% vs. 20.6%; p < .001) and had shorter waiting time (mean= 756 vs. 797 vs. 854 days; p < .001) respectively. CIT was significantly longer (p< .001) in both ECD groups; more ECD kidneys had prolonged CIT (>24 hours). By Kaplan Meier analysis, 1-, 3-, and 5-year death censored graft survival in re-ECD group was significantly inferior to Prim-ECD (83% vs. 91%, 72% vs. 83%, and 62% vs. 73%, logrank p < .001); however, patient survival was significantly superior (93% vs. 91%, 84% vs. 83%, and 76% vs. 73%; logrank p= .015) respectively. On univariate analysis, re-ECD kidneys experienced higher failure rate (HR= 1.19, 95%CI= 1.11-1.27, P< .001), but patients experienced significantly lower mortality rate than Prim-ECD kidneys (HR=. 89 95%CI= .80-98, p= .02). On multivariate analysis adjusting for the confounders graft failure risk remained significant (HR= 1.23, 95%CI= 1.12-1.36, p< .001); however, patient mortality rate reversed (HR=1.25, 95% CI=1.08-1.44, p= .001). Compared to the re-SCD group, re-ECD had significantly higher risk (Adjusted HR graft failure =1.72,95CI=1.57-1.89 and patient mortality =1.43, 95CI=1.17-1.75; p< .001). Conclusion: Although patients retransplanted with ECD were younger, thinner and less likely to be diabetic, graft outcomes were significantly worse than primary transplantation with ECD. This may have significant ramifications concerning patient and programmatic expectations.

Finding the “Diamond in the Rough” Kidneys Amongst Deceased Donors With a High Terminal Creatinine (hiCr).

The Maryland Aggregate Pathology Index is a published pre-implantation scoring tool that predicts graft outcome is reflective of donor renal pathology. A low(Lo) score (MAPI 0-7) indicates little donor disease, whereas a high(Hi) score (MAPI 12-15) indicates severe donor disease (Intermediate(In) is 8-11). As MAPI has been useful to further risk stratify ECD and older kidneys, we investigated whether MAPI can do the same for deceased donor(DD) kidneys with a hiCr. Methods: We analyzed 205 DDs transplants with a mean follow up of 683 days. 35 DDs with a hiCr (>2.0 mg/dl) were used due to favorable donor clinical parameters. Results: The hiCr gp was younger (41 yrs vs. 53 yrs, p<0.001), were less likely to have HTN (23% vs. 60%, p<0.04), and likely to have a shorter cold ischemia time (20 hrs vs. 24 hrs, p=0.047). Otherwise, this gp was similar to the low creatinine gp (loCr). The 4 yr survival for the loCr gp was 70% compared to 43.9% for the hiCr gp (p=0.8). Within each MAPI gp, there was no difference in 4 yr survival between the loCr or hiCr gps.Table: No Caption available.Hi & In MAPI kidneys faired worse regardless of the donor terminal creatinine. Conversely, within either the loCr and hiCr gps, the graft survival was significantly influenced by the MAPI score. For the loCr gp, the 4 yr survival was 84% for the Lo MAPI kidneys vs. 45% for the In & Hi MAPI kidneys combined, p<0.001. Similarly, in the hiCr gp, the 4 yr survival was 93% for Lo MAPI kidneys vs 14% for the In & Hi MAPI kidneys combined, p=0.001.Figure: No Caption available.By both uni and multivariate analysis, clinical donor parameters were poor predictors of graft outcome. MAPI score on the other hand, was the best predictor of graft function (p<0.001). hiCr had no significant impact. Conclusion: Although the use of hiCr donor kidneys can have good results, it is important to risk stratify within that group. As a pre-implantation scoring tool, MAPI successfully segregated the hiCr kidneys; Lo MAPI kidneys within that gp had excellent outcomes and were equivalent to Lo MAPI kidneys from the loCr group.

Calcineurin Free Protocol Is Associated With Increase in FOXP3 Expression in the Peripheral Blood of Recipients of Extended Criteria Donor Kidneys.

Background: The significance of the factor forkhead box (FOXP3) expression in the peripheral blood of renal transplant recipients (RTx) of extended (ECD) or standard (SCD) criteria donor kidneys is yet to be determined. Aim: To investigate the clinical significance of FOXP3 level in relation to the type of kidney donor, immunosuppressive protocol (ISS) and graft function in stable ECD RTx. Methods: Prospective, open label study with 36 stable RTx randomized according to the type of donor to receive tacrolimus (TAC; n= 19) or everolimus (EVL; n=17) based protocols combined to mycophenolate sodium, prednisone and induction therapy with basiliximab. Using qRT-PCR we measured FOXP3 expression in the peripheral blood of patients (pts) at the 3rd month after Tx. Results: Greater expression of FOXP3 was observed in recipients of ECD when compared to SCD (ECD=1.98 ± 2.8 vs SCD= 0.63 ± 0.71; p=0.02). EVL based immunosuppression (EVL= 1.49 ± 2.1 vs TAC= 0.51 ± 0.57; p=0.03) and absence of DGF post-Tx (DGF- = 1.94 ± 2.5 vs DGF+ = 0.54 ± 0.6; p=0.014) were also associated with high levels of FOXP3 expression. Cold ischemia time, acute rejection episodes and serum creatinine (sCr) at 3rd month were not associated with changes in FOXP3 expression. Multivariate logistic regression analysis showed that ECD (p= 0.025) absence of DGF (0.015) were independently associated with high levels of FOXP3. Correlation between sCr and FOXP3 was inverse in TAC treated pts and positive in those taking EVL (r= 0.74, P = 0.007). FOXP3 expression was low in kidneys with mild or no chronic lesions (IFTA score < 2) regardless the ISS. Patients treated with EVL presenting IFTA score ≥ 2 had increased expression of FOXP3 (p=NS vs TAC). Conclusions: Results suggest that recipients of ECD kidneys without having undergone DGF, treated with EVL presented an increased expression of FOXP3 in their peripheral blood. The higher FOXP3 levels associated with more chronic histological lesions may represent an anti-inflammatory response elicited by ongoing chronic allograft damage. DISCLOSURES:Abbud-Filho, M.: Grant/Research Support, Novartis. Dias, C.: Grant/Research Support, Novartis. Caldas, H.: Grant/Research Support, Novartis. Nunes, R.: Grant/Research Support, Novartis. Mazeti, C.: Grant/Research Support, Novartis. Fernandes-Charpiot, I.: Grant/Research Support, Novartis. Baptista, M.: Grant/Research Support, Novartis. Abbud-Filho, M.: Grant/Research Support, Novartis.

Outcomes at 3-Years in EBV+ Recipients of UNOS Criteria ECD Kidneys From a Randomized Trial (BENEFIT-EXT) Comparing Belatacept vs Cyclosporine.

Outcomes at 3-Years in EBV+ Recipients of UNOS Criteria ECD Kidneys From a Randomized Trial (BENEFIT-EXT) Comparing Belatacept vs Cyclosporine.

Preemptive Kidney Transplantation and the Utilization of ECD Kidneys: Who Are We Helping?

Preemptive Kidney Transplantation and the Utilization of ECD Kidneys: Who Are We Helping?

Evaluation of Donor-Specific Antibodies Through 5 Years With Belatacept in BENEFIT and BENEFIT-EXT.

Background: Donor-specific antibodies (DSA) are associated with negative post-transplant outcomes, including increased risk of antibody-mediated rejection and graft failure. De novo (DN) DSA occur in ˜11 % of kidney transplant recipients by 1 year and in ˜20% by 5 years (Everly et al, Transplantation 2013;95(3):410-7). The 3 year ITT results from BENEFIT and BENEFIT-EXT showed that belatacept was associated with lower rates of DN DSA than CsA (3% vs. 8%, Larsen C et al, ESOT 2011 [presentation O244]). Here we report the incidence of DN DSA through Year 5 in the long-term extensions (LTE) of these studies. Methods: In BENEFIT, patients received living donor or SCD kidneys, and in BENEFIT-EXT, patients received ECD kidneys. Patients received more (MI) or less intensive (LI) belatacept or CsA and could enter the LTE after 3 years. The presence of DSA was established centrally by comparing the HLA type of donors and recipients, identifying the recipient’s HLA antibodies, and then determining if any of those HLA antibodies were donor directed. HLA antibody screening was performed by solid phase flow cytometry (FLowPRATM), and specificity (Class I and II) assessed by LabScreenTM single antigen beads (One Lambda, Inc.). Results: From baseline through Year 5 in the LTE cohort of both studies, numerically fewer belatacept- vs. CsA-treated patients developed DN DSA (Table): in BENEFIT, 3 (1.9%) MI, 6 (3.6%) LI, and 16 (11.8%) CsA, and in BENEFIT-EXT, 7 (6.7%) MI, 1(0.9) LI, and 9 (10.3%) CsA-treated patients developed DN DSA. Conclusions: These data demonstrate a reduced rate of DN DSA with belatacept vs. CsA from baseline through 5 years, consistent with the findings observed through 3 years.Table: No Caption available.DISCLOSURE:Ganguly, B.: Employee, Bristol-Myers Squibb, Stockholder, Bristol-Myers Squibb. Townsend, R.: Employee, Bristol-Myers Squibb. Meier-Kriesche, U.: Employee, Bristol-Myers Squibb. Harler, M.: Employee, Bristol-Myers Squibb.

Kidney donor risk index is a good prognostic tool for graft outcomes in deceased donor kidney transplantation with short, cold ischemic time

We performed a retrospective cohort study to determine the prognostic value of standard criteria donor/expanded criteria donor (SCD/ECD) designation, with regard to one-yr GFR and graft survival rate, in a region with short, cold ischemic time (CIT), and how this designation compares with the kidney donor risk index (KDRI) and zero-time kidney biopsies. We reviewed 362 cases of deceased donor kidney transplantation (DDKT). Donor kidneys were classified as SCD or ECD. They were also assessed by the KDRI. Zero-time kidney biopsy was performed in 196 patients, and histologic score was assessed. Median follow-up duration was 46 months. Forty-two cases (11.6%) used ECD kidneys. The mean CIT was only 4.9 ± 2.7 h. Graft survival rates were not significantly different between ECD and SCD groups. The KDRI showed the best correlation with one-yr estimations of glomerular filtration rate (eGFR) (R(2) = 0.230, p < 0.001), and higher KDRI was associated with a higher risk of graft failure (hazard ratio 2.63, 95% confidence interval 1.01-6.87). However, higher histologic score was not associated with a higher risk of graft failure. KDRI has greater predictive value for short-term outcomes in DDKT with short CIT than the SCD/ECD designation or pathology.

Clinical and Histopathologic Comparative Analysis Between Kidney Transplant Recipients From Expanded-Criteria Donors and Standard-Criteria Donors

Owing to the disparity between the supply of kidney donors and demand, the use of organs from older deceased donors was initiated in recent years. The potentially poor outcome of these grafts is a major concern. This retrospective study compares graft and patient 1-year survivals between recipients from expanded-criteria donors (ECD; n = 30) and standard-criteria donors (SCD; n = 104). Rates of delayed graft function (DGF), acute rejection (AR), and chronic injury in the pre-implantation biopsy were also assessed. Increasing donor age was associated with increased rates of DGF, and DGF correlated with AR. Cold ischemia time >30 hours was associated with worse graft outcomes. Induction with Simulect correlated with better patient survival compared with Timoglobulina. Chronic injury pre-implantation biopsy correlated with worse renal function, but graft survival was similar. Death-censored graft survival at 1 year was 90% and patient survival 82%, and these were similar in ECD and SCD recipients. Selection of transplant candidates for ECD kidneys must be performed with caution. One-year graft survival was similar to that of SCD kidneys, but kidney function was worse during the same period. This may result in poorer graft survival over longer follow-up.

Transplantation With Kidneys Retrieved From Deceased Donors With Acute Renal Failure

The discard rate of kidneys recovered from deceased donors with acute renal failure (ARF) is higher compared with those without ARF mainly due to the uncertainty regarding short-term and long-term outcomes. We retrospectively analyzed 1-year patient, graft, and rejection-free survivals and renal function of transplantations performed with kidneys recovered from deceased donors with or without ARF, defined as serum creatinine level of more than 1.5 mg/dL. We performed multivariable analysis to evaluate whether ARF was an independent risk factor associated with inferior outcomes. Of a total of 1518 patients, 253 received kidneys from expanded-criteria donors (ECD; with ARF [n=116] and without ARF [n=137]) and 1265 from standard-criteria donors (SCD; with ARF [n=369] and without ARF [n=896]). The incidence of delayed graft function was higher in ECD (68.1% vs. 58.4%; P=0.072) and SCD (69.9% vs. 50.6%; P<0.001) recipients of kidneys with ARF compared with those without ARF, respectively. At 1 year, patient, graft, and rejection-free survivals were not statistically different in SCD or ECD recipients with or without ARF. Renal function at 1 year was similar in recipients of ECD (41.9±26.3 vs. 40.1±21.7 mL/min; P=0.565) or SCD (50.9±29.9 vs. 53.6±28.5 mL/min; P=0.131) kidneys with and without ARF, respectively. Compared with kidneys without ARF, receiving a kidney allograft with ARF was not associated with increased risk of death, graft lost, or inferior renal function 1 year after transplantation. In this cohort of patients, kidneys from deceased donors with ARF provided graft survival and renal function comparable with kidneys from donors without ARF 1 year after transplantation.

Kidney Transplantation Alone in ESRD Patients With Hepatitis C Cirrhosis

We read with great interest the article titled “Kidney Transplantation Alone in ESRD Patients with Hepatitis C Cirrhosis” (1). We have recently reviewed our own experience with KTA in well-compensated cirrhotics (submitted for publication). We agree that the presence of cirrhosis in HCV-positive patients is not a significant variable affecting either graft or patient survival. In our study, we compared 18 well-compensated cirrhotics versus 103 HCV-positive noncirrhotics. Our 1- and 3-year death-censored graft survival was 89 and 78% for the cirrhotics and 95% and 81% for NC. Our patient survival at 1 and 3 years were 100% and 83% for the cirrhotic group and 91% and 83% for NC. In our study, recipient age was not a factor in any outcomes. Serum albumin and platelet count were not a factor in allograft outcomes in the cirrhotic group. Additionally, both groups did not show any statistically significant differences in multiple demographic variables, patient survival, graft survival, adherence, acute rejection at 1 year, delayed graft function and liver decompensation or infection as a cause of graft loss or death. In our study, cancer was statistically more significant in the cirrhotic group. We attributed this to the use of thymoglobulin induction (immunosuppression was not addressed by Paramesh et al.). Additionally, many of the patients who developed cancer were retransplant recipients and KTA after liver transplantation. We agree that it is imperative to maximize the use of HCV-positive donor organs. In our study, more than two thirds of the recipients received HCV+ grafts without negatively affecting patient or allograft survival. We do not limit the use of HCV+ donors to genotype 1 patients. We also do not combine ECD with HCV. None of our cirrhotic patients received ECD kidneys. Although there was no association between donor ECD versus SCD in recipient outcomes in the paper by Paramesh et al., we believe that the HR of 2.78 for graft survival is important and may become relevant with a larger cohort studied over a longer period. In summary, in our report of 121 transplants, we confirm that well-compensated cirrhosis is not a negative prognostic indicator. Additionally, we very closely studied multiple donor and recipient variables and outcomes. We found a higher incidence of cancer in our cirrhotic group, perhaps attributed to aggressive induction. We are hopeful that this may lead to timely KTA and will minimize liver allograft wastage. Stalin Campos Afshin Parsikia Radi F. Zaki Jorge A. Ortiz Department of Transplant Albert Einstein Medical Center Philadelphia, PA