10-year Death-censored Graft Survival Research Articles

Long-term outcomes after hypothermic oxygenated machine perfusion and transplantation of 1,202 donor livers in a real-world setting (HOPE-REAL study)

Background & AimWe aimed to assess long-term outcome after transplantation of HOPE-treated donor livers based on real-world data (i.e., IDEAL-D stage 4). MethodsIn this international, multicentre, observational cohort study, we collected data from adult recipients of a HOPE-treated liver transplanted between January 2012 and December 2021. Analyses were stratified for brain-dead (DBD) and circulatory-dead (DCD) donor livers, sub-divided by their respective risk categories. The primary outcome was death-censored graft survival. Secondary outcomes included the incidence of primary non-function (PNF) and ischemic cholangiopathy (IC). ResultsWe report on 1202 liver transplantations (64% DBD) performed at 22 European centres. For DBD, a total number of 99 benchmark (8%), 176 standard (15%), and 493 extended-criteria (41%) cases were included. For DCD, 117 transplants were classified as low-risk (10%), 186 as high-risk (16%), and 131 as futile (11%), with significant risk profile variations among centres. Actuarial 1-, 3-, and 5-year death-censored graft survival for DBD and DCD was 95%, 92%, and 91%, vs. 92%, 87%, and 81%, respectively (logrank p=0.003). Within DBD and DCD-strata, death-censored graft survival was similar among risk groups (logrank p=0.26, p=0.99). Graft loss due to PNF or IC was 2.3% and 0.4% (DBD), and 5% and 4.1% (DCD). ConclusionsThis study shows excellent 5-year survival after transplantation of HOPE-treated DBD and DCD livers with low rates of graft loss due to PNF or IC, irrespective of their individual risk profile. HOPE-treatment has now reached IDEAL-D stage 4, which further supports the implementation of HOPE in routine clinical practice. Impact and ImplicationsThis study demonstrates the excellent long-term performance of HOPE-treatment of DCD and DBD liver grafts irrespective of their individual risk profile in a real-world setting, outside the evaluation of randomized controlled trials. While previous studies have established safety, feasibility, and efficacy against the current standard, according to the IDEAL-D evaluation framework, HOPE-treatment has now reached the final IDEAL-D Stage 4, which further supports the implementation of HOPE in routine clinical practice. Trial registrationClinicalTrials.gov Identifier: NCT05520320

#153 The risk of post-transplant recurrent immunoglobulin A nephropathy: the association with post-transplant steroid use

Abstract Background and Aims Immunoglobulin A nephropathy (IgAN) is the most common cause of kidney failure among glomerulopathies worldwide and it is reported that approximately 6-7% of all kidney transplantation is due to IgAN. It is well known that IgAN can recur in the kidney allograft and previous studies suggest that recurrent IgAN is the third most common cause of graft loss in patients with IgAN as primary disease. There is currently no effective treatment for recurrent IgAN, and the main goal is therefore to prevent recurrence in the allograft. Post-transplant steroid therapy is a cornerstone in many immunosuppressive regimens, but steroid treatment also come with several side effects leading to the use of steroid-free protocols. Controversy remains as to whether the use of steroid affects the risk of recurrent IgAN. Previous, retrospective studies report widely divergent associations between the use of steroids and the risk of recurrent IgAN and thus, more research on the association between steroid use and the risk of recurrent IgAN is warranted. We examined this by taking advantage of the fact that two different standard immunosuppression protocols have been employed at two Danish transplantation centers, of which one included steroids and the other did not. The patients treated at the two transplantations centers were otherwise similar with respect to ethnicity, socio-economic status and other aspects of treatment differing only by regional residency. This provided a unique opportunity to compare the association between steroid use, recurrence rate and graft survival. We furthermore aimed to identify potential risk factors for recurrent IgAN. Method A retrospective cohort study including all adult patients (age ≥ 18 years) with biopsy-proven IgAN and a first-time kidney-only transplantation from 1990 to 2020 at either Aarhus University Hospital or Odense University Hospital using a steroid containing or a steroid free post-transplant immunosuppressive protocol, respectively. Renal transplant patients with IgAN were identified from the Danish Nephrology Registry and data on medical treatment, graft survival and histopathological evidence of recurrent IgAN were extracted from electronic medical journals. Data is presented by Aalen-Johansen and Kaplan-Meier plot, and associations between risk factors for recurrent IgAN were analyzed by cox-regression. Results A total of 120 first-time kidney recipients were included in the study. Biopsy-proven, recurrent IgAN was identified in 17 (14.2%) recipients. The median time from transplantation to recurrence was 2.91 years (IQR 0.89−5.60). Only one of 18 (15%) recipients adhering to steroid-free protocol was diagnosed with recurrent IgAN during the study period. The accumulated use of steroid as part of the immunosuppression regime was not associated with the risk of recurrent IgAN (unadjusted HR (95% CI) =1.02 (0.94−1.12)). Transplantation with genetically related living donor was associated with a greater risk of recurrent IgAN compared with non-genetically related ((unadjusted HR (95% CI) = 3.90 (1.37−11.10)) and recipients with recurrent IgAN were more likely to be younger at time of been diagnosed with IgAN and had a shorter time from being diagnosed to kidney failure when compared to recipients with non-recurrent IgAN. There were no associations between the risk of recurrent IgAN and induction therapy or HLA-mismatches. The 10-year death censored graft survival was 45% for recipients with recurrent IgAN, compared to 80% for recipients with non-recurrent IgAN. Conclusion The risk of recurrent IgAN after kidney transplantation was not associated with the use of steroids as part of the immunosuppression protocol, whereas recipients receiving a kidney from a genetic related donor appeared to have a higher risk of recurrent IgAN.

Renal Transplant in Elderly End-Stage Renal Disease Patients: Impact of Comorbidities and Posttransplant Adverse Events on Outcomes.

Elderly renal transplant continues to be debated because of age-related factors affecting transplant success and long-term prognosis. We investigated the effects ofrecipient age and predictors of renal transplant outcomes in elderly renal transplant recipients. We retrospectively analyzed 506 patients who had a first renal transplant between January 2010 and December 2020; there were 165 recipients aged ≥60 years (elderly) and 341 recipients aged <60 years (young).We collected recipient, donor, and transplant characteristics and assessed 1-, 3-, and 5-year overall patient and death-censored graft survival and risk factors influencing outcomes ofrenal transplant in elderly recipients. Elderly recipients showed significantly lower 1-, 3-, and 5-year patient survival rates (96.3%, 89.8%, 80.9%) than young recipients (98.8%, 98.5%, 97.8%; P < .001). However, death-censored graft survival rates were not significantly different (P = .459) between elderly (96.3%, 94.3%, 93.2%) and young recipients (97.7%, 97.0%, 93.9%). Advanced recipient age was identified as an independent risk factor for patient survival, irrespective of donor age. In elderly recipients, male gender (hazard ratio 2.013; 95% CI, 1.110-3.649), pretransplant cardiovascular disease (hazard ratio 1.774; 95% CI, 1.030-3.553), and posttransplant chestinfection (hazard ratio 2.421; 95% CI, 1.439-4.076) were significant predictors of inferior patient survival. Proteinuria at 1 month (hazard ratio 1.006; 95% CI, 1.000-1.011) and low estimated glomerular filtration rate at 3 months (hazard ratio 0.943; 95% CI, 0.899-0.988) posttransplant were early predictors of worse death-censored graft survival. Elderly renaltransplantrecipients showed promising 5-year patient and death-censored graft survival, exceeding 80%, despite higher mortality risk compared with young recipients. Optimizing outcomes of elderly renal transplant necessitates a multifaceted approach encompassing meticulous pretransplant cardiovascular disease assessment, rigorous posttransplant chest infection prevention and management, and proactive monitoring for early posttransplant kidney dysfunction, to permit timely intervention.

Peri-operative and long-term outcomes of kidney transplantation in patients with cystic fibrosis.

There is a lack of data regarding the peri-operative and long-term outcomes of kidney transplantation in cystic fibrosis (CF) patients. Herein, we report the peri-operative and long-term outcomes of kidney transplantation in CF patients. All CF patients who received a kidney transplant at the national kidney transplant center between 1993 and 2022 were identified. Recipients of the contralateral donor kidney were selected as a control group. Primary outcomes included 1-, 5-, and 10- year death-censored graft survival and overall survival. Secondary outcomes included peri-operative morbidity, acute graft rejection, delayed graft function (DGF), and length of stay (LOS). Fourteen patients received a kidney transplant over the study period. Median age at transplantation was 35 (IQR 31, 40) years. The 1-, 5-, and 10-year death-censored graft survival was 92, 74, and 74% in the CF group compared to 100, 92, and 92% in the control group (p=.44). The 1-, 5-, and 10-year overall survival in the CF group was 85, 66, and 57% compared to 100, 92, and 82% in the control group (p=.036). There was no significant difference in peri-operative outcomes including LOS (10vs. 11 days, p=.84), ICU admission (1vs. 0 patients, p>.99), acute rejection episodes (2vs. 1 patients, p>.99), and DGF (1vs. 2 patients, p=.60). CF patients have good long-term graft survival, however, overall survival was worse compared to a matched cohort. These data provide important information for transplant surgeons when considering suitable donor allografts in this unique patient population.

Difficult-to-Treat Rejections in Kidney Transplant Recipients: Our Experience with Everolimus-Based Quadruple Maintenance Therapy.

All chronic and treatment-resistant acute rejections are "difficult-to-treat" and lead to progressive loss of graft function in kidney transplant recipients (KTR), as no effective treatment exists for such rejections to date. We review our experience with a novel strategy to treat such rejections by adding everolimus as a "rescue" to conventional triple maintenance therapy with prednisolone, mycophenolate mofetil and calcineurin inhibitor. We retrospectively analysed data in 28 KTR who received everolimus-based quadruple therapy at our institution for biopsy-proven chronic active T cell-mediated or antibody-mediated rejection (n = 19) or treatment-resistant acute rejections (n = 9) between 2011-2017. The primary outcome was 5-year death-censored graft survival. Main secondary outcomes were response to treatment defined by stable or improved graft function, 5-year patient survival and discontinuation rate of treatment. The Kaplan-Meier estimate for 5-year death-censored graft survival was 79% in all patients, 90% for patients with chronic active T cell-mediated rejections, 78% for chronic active antibody-mediated rejection and 67% for acute rejections. Response to treatment was achieved in 43% and 5-year patient survival was 94%. Treatment was stopped in 12 (43%) patients due to adverse events. Everolimus-based maintenance quadruple therapy, despite high rate of everolimus discontinuation due to adverse events, may be a valid approach in a subset of kidney transplant recipients with such difficult-to-treat rejections, which otherwise would lead to a high rate of graft loss.

Characteristics of Kidney Transplant Recipients with Prolonged Pre-Transplant Dialysis Duration as Identified by Machine Learning Consensus Clustering: Pathway to Personalized Care.

Longer pre-transplant dialysis duration is known to be associated with worse post-transplant outcomes. Our study aimed to cluster kidney transplant recipients with prolonged dialysis duration before transplant using an unsupervised machine learning approach to better assess heterogeneity within this cohort. We performed consensus cluster analysis based on recipient-, donor-, and transplant-related characteristics in 5092 kidney transplant recipients who had been on dialysis ≥ 10 years prior to transplant in the OPTN/UNOS database from 2010 to 2019. We characterized each assigned cluster and compared the posttransplant outcomes. Overall, the majority of patients with ≥10 years of dialysis duration were black (52%) or Hispanic (25%), with only a small number (17.6%) being moderately sensitized. Within this cohort, three clinically distinct clusters were identified. Cluster 1 patients were younger, non-diabetic and non-sensitized, had a lower body mass index (BMI) and received a kidney transplant from younger donors. Cluster 2 recipients were older, unsensitized and had a higher BMI; they received kidney transplant from older donors. Cluster 3 recipients were more likely to be female with a higher PRA. Compared to cluster 1, cluster 2 had lower 5-year death-censored graft (HR 1.40; 95% CI 1.16-1.71) and patient survival (HR 2.98; 95% CI 2.43-3.68). Clusters 1 and 3 had comparable death-censored graft and patient survival. Unsupervised machine learning was used to characterize kidney transplant recipients with prolonged pre-transplant dialysis into three clinically distinct clusters with variable but good post-transplant outcomes. Despite a dialysis duration ≥ 10 years, excellent outcomes were observed in most recipients, including those with moderate sensitization. A disproportionate number of minority recipients were observed within this cohort, suggesting multifactorial delays in accessing kidney transplantation.

Language barriers and kidney transplantation in children.

Understanding disparities in pediatric kidney transplants is important to provide equitable care. We compared transplant outcomes between English-speaking (ES) and interpreter-needing (IN) pediatric kidney transplant recipients. Through retrospective review, primary kidney transplant recipients, 0-21years transplanted between 2005 and 2019, were divided into ES and IN cohorts. Continuous and categorical variables were compared using Wilcoxon rank-sum, Welch two-sample t-test, and chi-squared analyses. Patient survival, graft survival, and rejection-free survival were evaluated using Kaplan-Meier methods and Cox regression. Days hospitalized were evaluated using negative binomial regression. Our sample included 211 ES and 37 IN transplant recipients. Compared withthe ES, the IN cohort was older at transplant (14.56 vs. 11.03years; p < 0.01), had more time between kidney failure and transplant (0.9 vs. 0.3years; p < 0.01), and more often received deceased over living donor transplants (78.4% vs. 30.4%; p < 0.01). Multivariate Cox proportional-hazard models evaluating adjusted 5-year patient survival demonstrated decreased 5-year post-transplant survival in theIN cohort (aHR = 10.10, 95% CI: 1.5, 66.8; p = 0.02). We did not identify differences in 5-year death-censored graft survival (aHR = 0.57; 95% CI: 0.14, 2.4; p = 0.4) nor rejection-free survival (aHR = 0.8; 95% CI: 0.4, 1.5; p = 0.5). We found significantly fewer hospitalization events in the IN cohort during the first year post-transplant (aRR: 0.62; 95% CI: 0.4, 0.9; p = 0.01) but no difference 5-year post-transplant. TheIN cohort had more missed outpatient appointments (10.4% vs. 2.8%; p = 0.03) and undetectable serum immunosuppressant levels (mean: 3.8% vs. 1.3%; p = 0.02) 5years post-transplant. Pediatric kidney transplant recipients requiring interpreter services for healthcare delivery demonstrate fewer post-transplant interactions with their healthcare team (fewer hospitalizations and more no-show visits) and lower 5-year patient survival compared with recipients not requiring interpreters. A higher resolution version of the Graphical abstract is available as Supplementary information.

Cold Ischemia Time, Kidney Donor Profile Index, and Kidney Transplant Outcomes: A Cohort Study

An average of 3,280 recovered deceased donor kidneys are discarded annually in the United States. Increased cold ischemia time is associated with an increased rate of organ decline and subsequent discard. Here we examined the effect of prolonged cold ischemia time on kidney transplant outcomes. Retrospective observational study. Recipients of deceased donor kidney transplants in the United States from 2000 to2018. Recipients of deceased donor kidneys were divided based on documented cold ischemia time:≤16, 16-24, 24-32, 32-40, and>40 hours. The incidence of delayed graft function, primary nonfunction, and 10-year death-censored graft survival. The Kaplan-Meier method was used to generate survival curves, and the log rank test was used to compare graft survival. The rate of observed delayed graft function increased with cold ischemia time (20.9%, 28.1%, 32.4%, 37.5%, and 35.8%). Primary nonfunction also showed a similar increase with cold ischemia time (0.6%, 0.9%, 1.3%, 2.1%, and 2.3%), During a median follow-up time of 4.6 years, 37,301 recipients experienced death-censored graft failure. Analysis based on kidney donor profile index (KDPI) demonstrated significant differences in 10-year death-censored graft survival, with a death-censored graft survival in recipients of a kidney with a KDPI<85% of 71.0% (95% CI, 70.5%-71.5%), 70.5% (95% CI, 69.9%-71.0%), 69.6% (95% CI, 68.7%-70.4%), 65.5% (95% CI, 63.7%-67.3%), and 67.2% (95% CI, 64.6%-69.6%), compared to 53.5% (95% CI, 51.1%-55.8%), 50.7% (95% CI, 48.3%-53.1%), 50.3% (95% CI, 46.6%-53.8%), 50.7% (95% CI, 45.1%-56.1%), and 48.3% (95% CI, 40.0%-56.1%), for recipients of a kidney with a KDPI>85%. Heterogeneity of acceptance patterns among transplant centers, presence of confounding variables leading to acceptance of kidneys with prolonged cold ischemia times. Cold ischemia time was associated with an increased risk of delayed graft function and primary nonfunction. However, the effect of increased cold ischemia time is modest and has less impact than the KDPI. Transplant programs should not consider prolonged cold ischemia time alone as a predominant reason to decline an organ, especially with a KDPI<85%.

Predicting older-donor kidneys' post-transplant renal function using pre-transplant data.

This paper provides a methodology for predicting post-transplant kidney function, that is, the 1-year post-transplant estimated Glomerular Filtration Rate (eGFR-1) for each donor-candidate pair. We apply customized machine-learning algorithms to pre-transplant donor and recipient data to determine the probability of achieving an eGFR-1 of at least 30 ml/min. This threshold was chosen because there is insufficient survival benefit if the kidney fails to generate an eGFR-1 ≥ 30 ml/min. For some donor-candidate pairs, the developed algorithm provides highly accurate predictions. For others, limitations of previous transplants' data results in noisier predictions. However, because the same kidney is offered to many candidates, we identify those pairs for whom the predictions are highly accurate. Out of 6977 discarded older-donor kidneys that were a match with at least one transplanted kidney, 5282 had one or more identified candidate, who were offered that kidney, did not accept any other offer, and would have had ≥80% chance of achieving eGFR-1 ≥ 30 ml/min, had the kidney been transplanted. We also show that transplants with ≥80% chance of achieving eGFR-1 ≥ 30 ml/min and that survive 1 year have higher 10-year death-censored graft survival probabilities than all older-donor transplants that survive 1year (73.61% vs. 70.48%, respectively).

215.11: Evaluating Kidney Transplant Characteristics and Outcomes in Patients With Henoch-Schönlein Purpura

Introduction: Henoch-Schönlein Purpura (HSP) is a small-vessel vasculitis characterized by deposits of immunoglobulin A (IgA) in target tissues. HSP is more frequently seen in children and usually has benign and self-limiting renal involvement; however, it is estimated that up to 2% of children with HSP nephritis can develop End-Stage Renal Disease (ESRD) and require renal replacement therapy. Due to the infrequency of HSP causing ESRD, large-scale studies of HSP and kidney transplant (KT) outcomes are scarce. Methods: We used data from Scientific Registry of Transplant Recipients to evaluate differences for HSP patients listed for KT. Adult and pediatric patients listed from October 1987 to April 2021 were included. Recipients without HSP were randomly selected and matched in a 3:1 ratio to HSP recipients according to age (exact year), gender, ethnicity, donor source (living versus deceased), and year of transplantation (±3 years). Inferential statistics were used to evaluate differences between HSP and non-HSP patients. Regression modeling using a forward conditional approach and Kaplan-Meier survival analysis with a Mantel-Cox log-rank test were performed to calculate survivals and compare outcomes. Results: During the study time period, 504,878 KT were performed; 893 (0.17%) were for HSP. Compared with non-HSP patients, HSP KT recipients were younger (30.6±14.2vs 47.2±15.8; p<0.001) and more commonly Caucasian (87.5% vs 68.6%; p<0.001), received a living donor allograft (44.5 vs 32.9; p<0.001), and female (45.3% vs. 39.5%, p=0.001). Most HSP KT patients were preemptive (79.8%). A total of 773 HSP recipients were matched to 2,319 non-HSP recipients. For HSP patients, 1-, 3-, and 5-year death-censored graft survival (DCGS) was 87.3%, 70.4%, and 53.3%, respectively. For matched non-HSP patients, DCGS was 86.9%, 70.2%, and 52.5%, respectively (all p>0.05). Overall patient survival for HSP patients was 89.8%, 72.4%, and 55.6% at 1, 3, and 5 years, respectively. Overall patient survival for matched non-HSP patients was 89.3%, 72.9%, and 55.4% at 1, 3, and 5 years, respectively (all p>0.05). Acute rejection and graft thrombosis were the two leading causes of graft loss for both HSP (28.6% and 19.0%, resp.) and non-HSP patients (18.8% and 31.6%, resp.). In HSP patients who did not suffer recurrence, 1-, 3-, 5-, and 10-year DCGS was 95.8%, 88.8%, 81.3%, and 64.0%, respectively. Using regression model analysis of HSP KT patients for recurrence, older age (OR, 95% CI 1.05, 1.03-1.07, p<0.001) was significantly associated with recurrence; while a living donor allograft (0.50, 0.32-0.79, p=0.003) and a higher BMI (0.95, 0.91-0.99, p=0.020) were protective. Conclusion: In a contemporary cohort of HSP KT patients, we demonstrate comparable graft and patient survival for HSP patients, compared to matched non-HSP patients, and superior survival if recurrence can be avoided.

The Need for Routine Native Nephrectomy in the Workup for Kidney Transplantation in Autosomal Dominant Polycystic Kidney Disease Patients

Introduction: There is no consensus if nor when a native nephrectomy should be performed in the workup for kidney transplantation in ADPKD patients. In our PKD Expertise Center, a restrictive approach is pursued in which nephrectomy is performed only in patients with severe complaints, i.e., in case of serious volume-related complaints, lack of space for the allograft, recurrent cyst infections, persistent cyst bleedings, or chronic refractory pain. We analyzed in a retrospective cohort study whether this approach is justified. Methods: All ADPKD patients who received kidney transplantation between January 2000 and January 2019 were reviewed. Patients were subdivided into three groups: no nephrectomy (no-Nx), nephrectomy performed before (pre-Tx), or after kidney transplantation (post-Tx). Simultaneous nephrectomy together with transplantation were not performed in our center. Results: 391 patients (54 ± 9 years, 55% male) were included. The majority of patients did not undergo a nephrectomy (n = 257, 65.7%). A nephrectomy was performed pre-Tx in 114 patients (29.2%). After Tx, nephrectomy was performed in only 30 patients (7.7%, median 4.4 years post-Tx). Surgery-related complication rates did not differ between both groups (38.3% pre-Tx vs. 27.0% post-Tx, p = 0.2), nor were there any differences in 10-year patient survival (74.4% pre-Tx vs. 80.7% post-Tx vs. 67.6% no-Nx, p = 0.4), as well as in 10-year death-censored graft survival (84.4% pre-Tx vs. 85.5% post-Tx vs. 90.0% no-Nx, p = 0.9). Conclusions: This study indicates that with a restrictive nephrectomy policy in the workup for kidney transplantation, only a part of ADPKD patients need a native nephrectomy.

Distinct Phenotypes of Kidney Transplant Recipients in the United States with Limited Functional Status as Identified through Machine Learning Consensus Clustering.

Background: There have been concerns regarding increased perioperative mortality, length of hospital stay, and rates of graft loss in kidney transplant recipients with functional limitations. The application of machine learning consensus clustering approach may provide a novel understanding of unique phenotypes of functionally limited kidney transplant recipients with distinct outcomes in order to identify strategies to improve outcomes. Methods: Consensus cluster analysis was performed based on recipient-, donor-, and transplant-related characteristics in 3205 functionally limited kidney transplant recipients (Karnofsky Performance Scale (KPS) < 40% at transplant) in the OPTN/UNOS database from 2010 to 2019. Each cluster’s key characteristics were identified using the standardized mean difference. Posttransplant outcomes, including death-censored graft failure, patient death, and acute allograft rejection were compared among the clusters Results: Consensus cluster analysis identified two distinct clusters that best represented the clinical characteristics of kidney transplant recipients with limited functional status prior to transplant. Cluster 1 patients were older in age and were more likely to receive deceased donor kidney transplant with a higher number of HLA mismatches. In contrast, cluster 2 patients were younger, had shorter dialysis duration, were more likely to be retransplants, and were more likely to receive living donor kidney transplants from HLA mismatched donors. As such, cluster 2 recipients had a higher PRA, less cold ischemia time, and lower proportion of machine-perfused kidneys. Despite having a low KPS, 5-year patient survival was 79.1 and 83.9% for clusters 1 and 2; 5-year death-censored graft survival was 86.9 and 91.9%. Cluster 1 had lower death-censored graft survival and patient survival but higher acute rejection, compared to cluster 2. Conclusion: Our study used an unsupervised machine learning approach to characterize kidney transplant recipients with limited functional status into two clinically distinct clusters with differing posttransplant outcomes.

The Kidney Donor Profile Index (KDPI) Correlates With Histopathologic Findings in Post-reperfusion Baseline Biopsies and Predicts Kidney Transplant Outcome.

BackgroundThe increasing organ shortage in kidney transplantation leads to the necessity to use kidneys previously considered unsuitable for transplantation. Numerous studies illustrate the need for a better decision guidance rather than only the classification into kidneys from standard or expanded criteria donors referred to as SCD/ECD-classification. The kidney donor profile index (KDPI) exhibits a score utilizing a much higher number of donor characteristics. Moreover, graft biopsies provide an opportunity to assess organ quality.MethodsIn a single center analysis 383 kidney transplantations (277 after deceased and 106 after living donation) performed between January 1st, 2006, and December 31st, 2016, retrospectively underwent SCD/ECD and KDPI scoring. Thereby, the quality of deceased donor kidneys was assessed by using the KDPI and the living donor kidneys by using the living KDPI, in the further analysis merged as (L)KDPI. Baseline biopsies taken 10 min after the onset of reperfusion were reviewed for chronic and acute lesions. Survival analyses were performed using Kaplan-Meier analysis and Cox proportional hazards analysis within a 5-year follow-up.ResultsThe (L)KDPI correlated with glomerulosclerosis (r = 0.30, p < 0.001), arteriosclerosis (r = 0.33, p < 0.001), interstitial fibrosis, and tubular atrophy (r = 0.28, p < 0.001) as well as the extent of acute tubular injury (r = 0.20, p < 0.001). The C-statistic of the (L)KDPI concerning 5-year death censored graft survival was 0.692. Around 48% of ECD-kidneys were classified as (L)KDPI<85%. In a multivariate Cox proportional hazard analysis including (preformed) panel reactive antibodies, cold ischemia time, (L)KDPI, and SCD/ECD-classification, the (L)KDPI was significantly associated with risk of graft loss (hazard ratio per 10% increase in (L)KDPI: 1.185, 95% confidence interval: 1.033–1.360, p = 0.025). Survival analysis revealed decreased death censored (p < 0.001) and non-death censored (p < 0.001) graft survival in kidneys with an increasing (L)KDPI divided into groups of <35, 35–85, and >85%, respectively.ConclusionWith a higher granularity compared to the SCD/ECD-classification the (L)KDPI is a promising tool to judge graft quality. The correlation with chronic and acute histological lesions in post-reperfusion kidney biopsies underlines the descriptive value of the (L)KDPI. However, its prognostic value is limited and underlines the urgent need for a more precise prognostic tool adopted to European kidney transplant conditions.

Tumor Necrosis Factor-α Gene Polymorphism is Associated with Short- and Long-Term Kidney Allograft Outcomes.

IntroductionKidney transplantation has excellent short-term results with current immunosuppression regimes, but long-term outcomes have barely improved over the past two decades. Hence, there is a need for new therapeutic options to increase long-term survival of kidney grafts. Drug development for kidney transplantation has slowly plateaued, limiting progress while making drug repurposing an attractive alternative. We, therefore, investigated the impact of tumor necrosis factor-alpha (TNF-α) gene (TNF) polymorphisms on kidney graft survival after transplantation.MethodsWe performed a prospective cohort study to assess the association of TNF polymorphisms (rs1800629 G>A and rs3093662 A>G) with primary non-function and death-censored kidney allograft survival in 1271 kidney transplant pairs from the University Medical Center Groningen in The Netherlands.ResultsThe G-allele of the TNF rs3093662 polymorphism in donor kidneys was associated with a higher risk of immediate graft loss (odds ratio: 2.05; 95%-CI: 1.06–3.97; P = 0.032). Furthermore, the G-allele of this TNF rs3093662 polymorphism in the donor was also associated with worse 5-year, 10-year, and 15-year death-censored kidney graft survival (P < 0.05). The cumulative incidence of graft loss was 15.9% in the reference AA-genotype group and 25.2% in the AG/GG-genotype group, respectively. In multivariable analysis, the association between the TNF rs3093662 polymorphism in the donor and 15-year death-censored kidney graft survival remained significant (hazard ratio: 1.51; 95%-CI: 1.05–2.19, P = 0.028).DiscussionIn conclusion, kidney allografts possessing a high-producing TNF polymorphism have a greater risk of immediate and late graft loss. Our study adds to a growing body of literature indicating the potential of TNF-α blockade in improving kidney transplantation outcomes.

Post-transplant outcomes in recipients of living donor kidneys and intended recipients of living donor kidneys

BackgroundLong-term kidney transplant survival at the population level is consistently favorable, but this survival varies widely at an individual level due to both recipient and donor factors. The distinct contribution of recipient and donor factors to individual post kidney transplant outcome remains unclear. Comparing outcomes in deceased donor (DD) recipients with potential but non-actualized living donors (DD1) to those recipients with actualized living donors (LD), and to DD recipients without potential living donors (DD0) may provide transplant candidates with more information about their own post-transplant prognosis.MethodsWe conducted an observational retrospective cohort study of kidney transplant candidates presenting to our centre for evaluation between 01/01/06 and 31/12/18, and who also received a transplant during that time. Patients were followed to 31/08/2019. Candidates were classified as DD0, DD1, or LD based on whether they had an identified living donor at the time of initial pre-transplant assessment, and if the donor actualized or not. Primary outcome was 5-year death-censored graft survival, adjusted for common pre- and post-transplant donor and recipient risk factors. Secondary outcomes analyzed included patient survival and graft function.ResultsThere were 453 kidney transplant recipients (LD = 136, DD1 = 83, DD0 = 234) who received a transplant during the study period. DD0 and DD1 did not differ in key donor organ characteristics. The 5-year death censored graft survival of DD1 was similar to LD (p = 0.19). DD0 graft survival was inferior to LD (p = 0.005), but also trended inferior to DD1 (p = 0.052). By multivariate Cox regression analysis, LD demonstrated similar 5-year graft survival to DD1 (HR for graft loss 0.8 [95% CI 0.25–2.6], p = 0.72) but LD graft survival was superior to DD0 (HR 0.34 [0.16–0.72], p = 0.005). The 5-year patient survival in DD1 was similar to LD (p = 0.26) but was superior to DD0 (p = 0.01).ConclusionsDD recipients with potential but non-actualized living donors exhibit similar mid-term graft and patient survival compared to LD recipients. Having an identified living donor at the time of pre-transplant assessment portends a favorable prognosis for the recipient.

Outcomes after simultaneous pancreas–kidney transplantation from donation after circulatory death donors: A UK registry analysis

There are concerns that simultaneous pancreas-kidney (SPK) transplants from donation after circulatory death (DCD) donors have a higher risk of graft failure than those from donation after brain death (DBD) donors. A UK registry analysis of SPK transplants between 2005 and 2018 was performed. Pancreas survivals of those receiving organs from DCD or DBD donors were compared. Multivariable analyses were used to adjust for baseline differences between the two groups and to identify factors associated with pancreas graft loss. A total of 2228 SPK transplants were implanted; 403 (18.1%) were from DCD donors. DCD donors were generally younger, slimmer, less likely to have stroke as a cause of death, with lower terminal creatinines and shorter pancreas cold ischemic times than DBD donors. Median (IQR) follow-up was 4.2 (1.6-8.1) years. On univariable analysis, there were no statistically significant differences in 5-year death-censored pancreas graft survival between the two donor types (79.5% versus 80.4%; p=.86). Multivariable analysis showed no statistically significant differences in 5-year pancreas graft loss between transplants from DCD (n=343) and DBD (n=1492) donors (hazard ratio 1.26, 95% CI 0.76-1.23; p=.12). The findings from this study support the increased use of SPK transplants from DCD donors.

Inferior survival outcomes of pancreas transplant alone in uremic patients

Theoretically, pancreas transplant alone in uremic (PTAU) patients could also be one of the options for those waiting for both pancreas and kidney grafts, but it has never been reported. There were 160 cases of pancreas transplant in this study, including 16% PTAU. The 5-year patient survival was 66.2% after PTAU, 94.5% after SPK, 95.8% after PAK, and 95.4% after PTA. Rejection of pancreas graft was significantly lower in PTAU group (3.8%), followed by 16.7% in pancreas after kidney transplant (PAK), 29.8% in simultaneous pancreas and kidney transplant (SPK) and 37.0% in pancreas transplant alone (PTA). Fasting blood sugar and serum HbA1c levels after PTAU were not significantly different from those by other subgroups. The 5-year death-censored pancreas graft survival was 100% after PTAU and PAK, and 97.0% after SPK and 77.9% after PTA. However, the 5-year death-uncensored pancreas graft survival was 67.0% after PTAU, 100% after PAK, 91.3% after SPK, and 74.0% after PTA. The superior graft survival in the PTAU group was achieved only if deaths with a functioning graft were censored. In conclusion, given the inferior patient survival outcome, PTAU is still not recommended unless SPK and PAK is not available. Although PTAU could be a treatment option for patients with diabetes complicated by end-stage renal disease (ESRD) in terms of surgical risks, endocrine function, and immunological and graft survival outcomes, modification of the organ allocation policies to prioritize SPK transplant in eligible patients should be the prime goal.

Evaluation of severity of delayed graft function in kidney transplant recipients.

The most common definition of delayed graft function (DGF) relies on dialysis during the first week post-transplant and does not consider DGF severity. The impact of DGF severity on long-term graft outcome remains controversial. We analysed 627 deceased-donor kidney transplant recipients (KTRs) transplanted in 2005-2015 at our centre for DGF severity, associated risk factors and long-term consequences of DGF. We found 349 (55.7%) KTRs with DGF, which were classified into four groups according to DGF duration (0-1, 2-7, 8-14, >14days) and were compared with KTR with no DGF. A longer duration of DGF was associated with progressive worsening of 10-year death-censored graft survival {no DGF: 88.3% [95% confidence interval (CI) 82.4-94.2]; 0-1 day: 81.3% [95% CI 68.2-94.4], 2-7 days: 61.5% [95% CI 43.1.1-79.9], 8-14 days: 66.6% [95% CI 47.4-85.8], >14days: 51.2% [95% CI 33-69.4]; P<0.001}. In kidneys with a Kidney Donor Profile Index (KDPI) ≥85%, all DGF severity groups demonstrated reduced graft survival. However, inthe <85% KDPIkidneys, only>14days DGF duration showed worse outcomes. DGF had a duration-dependent effect on graft survival, which varied depending on the KDPI. Of note, 0- to 1-day DGF showed comparable results to no DGF in the whole cohort.

Maternal versus paternal living kidney transplant donation is associated with lower rejection in young pediatric recipients: A Collaborative Transplant Study report.

Approximately 1700 children per year with end-stage kidney disease undergo kidney transplantation in Europe and the United States of America; 30%-50% are living donor kidney transplantations. There may be immunological differences between paternal and maternal donors due to transplacental exchange of cells between the mother and fetus during pregnancy leading to microchimerism. We investigated whether the outcome of living-related kidney transplantation in young children is different after maternal compared with paternal organ donation. Using the international Collaborative Transplant Study (CTS) database, we analyzed epidemiological data of 7247 children and adolescents aged <18years who had received a kidney transplant from either mother or father. Risk of treated rejection episodes and death-censored graft failure were computed using the Kaplan-Meier method and multivariable Cox regression. In the recipient age group 1-4years, the rate of treated rejection episodes in recipients of kidneys from maternal donors (N=195) during the first 2years post-transplant was significantly lower (hazard ratio HR=0.47, p=.004) than in patients receiving kidneys from paternal donors (N=179). This association between donor sex and risk of treated rejections was not observed in children aged 5-9years. The 5-year death-censored graft survival in children aged 1-4years with a maternal or paternal donor was comparable. Maternal kidney donation in young pediatric renal transplant recipients is associated with an approximately 50% lower rate of treated rejection than paternal kidney donation. Whether this phenomenon is due to maternal microchimerism-induced donor-specific hyporesponsiveness must be evaluated in prospective mechanistic studies.

Analysis of risk factors for donation after circulatory death kidney transplantation in Japan.

BackgroundIn Japan, donations after circulatory death kidney transplantation are widely performed due to legislation delays. The number of donations after brain death kidney transplantations is increasing, but the target remains unmet. We reviewed the outcomes of donation after circulatory death in Japan.MethodsWe analyzed 2923 deceased kidney transplantations (2239: donation after circulatory death (DCD), 684: donation after brain death (DBD)) performed in Japan from 2000 to 2019. The outcomes of the DCD and DBD groups were compared. We examined the risk factors for graft loss in the DCD group.ResultsThe 5-year patient survival and death-censored graft survival rates of the DCD group, obtained by propensity score matching, were 93.6% and 95.2%, respectively, which were equivalent to 94.2% and 93.8%, respectively, obtained in the DBD group. Older donors (≥ 50 years) and prolonged cold ischemia time (≥ 12 h) were risk factors for graft loss; in the presence of these, graft survival was lower in the DCD group.ConclusionsOlder donors and prolonged cold ischemia time reduced graft survival in the DCD group. Proper evaluation of donors and careful preparation for transplant surgery are, therefore, essential to ensure good transplant outcomes.