Death-censored Allograft Survival Research Articles

Kidney transplant outcomes in children with simultaneous versus sequential heart-kidney transplants.

Heart transplant recipients frequently require kidney transplantation for concomitant advanced chronic kidney disease. Data on simultaneous (heart and kidney transplants performed simultaneously) versus sequential (heart transplant performed before kidney) heart-kidney transplants in children are limited. Herein, we compare kidney transplant outcomes between the two groups. We used the Scientific Registry of Transplant Recipients to identify all pediatric (age <21 years) heart transplant recipients who also received a kidney transplant within 10 years of the heart transplant. We divided the study cohort into simultaneous heart-kidney and sequential heart-kidney recipients. We compared patient and death-censored graft survival using the Cox regression, adjusting for age at kidney transplant, sex, race, pre-transplant dialysis, donor type, and prior kidney transplant. We evaluated delayed graft function (defined as dialysis within the first week posttransplant) using logistic regression. Our analysis cohort included 165 recipients (86 simultaneous and 79 sequential). The incidence of delayed graft function was higher in simultaneous recipients (22.4 vs. 7.7%, p=0.017), but the difference lost statistical significance on multivariable analysis. We found no difference in patient survival (aHR 0.97; 95% CI 0.39, 2.41; p=0.95) after kidney transplant but higher death-censored kidney graft survival in sequential heart-kidney recipients compared with simultaneous heart-kidney recipients (aHR 4.26; 95% CI 1.21, 14.9; p=0.02). Sequential heart-kidney transplants are associated with higher death-censored kidney allograft survival in children compared with simultaneous heart-kidney transplants.

#1016 Kidney transplantation in highly sensitized patients with preformed donor-specific antibodies through personalized delisting strategies

Abstract Background and Aims This study explores a personalized delisting strategy enabling kidney transplantation in highly sensitized patients with preformed donor-specific anti-HLA antibodies (DSA) trying to minimize the risk of antibody-mediated rejection (ABMR). Method Retrospective single-centre analysis of 50 kidney transplant recipients with preformed DSA (preDSA) after employing a delisting strategy to enhance their access to transplantation, and without received a pre-transplant or immediate post-transplant desensitization protocol. The delisting approach focused on allowing less deleterious antibodies according to their mean fluorescence intensity (MFI), anti-HLA class and C1q study results. The strategy consisted on eliminating as prohibited HLA antigens those recognized by antibodies with the lowest MFI in the following order: 1st- MFI &amp;lt; 5000; 2nd- MFI &amp;lt; 10000; 3rd-Any MFI. Additionally, delisting prioritized a single locus in the following order: 1st- one of the HLA class I loci (A, B, or Cw); 2nd- the rest of the class I loci; 3rd- HLA-DP, followed by DR. C1q studies were performed before delisting and transplantation was contraindicated in the presence of DSA detected in the C1q assay. Two comparative cohorts included 50 sensitized recipients without pre-transplant DSA (SwoDSA) and 50 non-sensitized recipients (NS). Results The delisting strategy allowed transplantation with preformed DSA and demonstrated comparable rejection rates to SwoDSA and NS groups (16%, 14% and 8%, respectively; log-rank = 0.28). However, the occurrence of acute ABMR was 12% in the preDSA group, significantly higher than in SwoDSA (1%) and NS (0%) (log-rank = 0.0093). The immunological risk assumed in delisting correlated with ABMR incidence (patients with ABMR had significantly higher sum MFI [mean ± SD: 9301 ± 6340 vs 4492 ± 5641; p = 0.049]), emphasizing the importance of tailored strategies. DSA persistence after transplantation correlated with higher MFI and increased ABMR risk. Of note, 16% of preDSA patients developed de novo DSA versus only the 4% of SwoDSA and 0% of NS patients (p = 0.004). After a mean follow-up of 3.1 ± 2.1 years, the 1-, 3- and 5-year death-censored allograft survival rates were 100%, 90% and 78%, respectively, in the preDSA group; 98%, 84% and 84% in the SwoDSA group and 100% in NS group (log-rank = 0.02). Conclusion The present study demonstrates the feasibility and acceptable outcomes of kidney transplantation in highly sensitized patients with preformed DSA through a personalized delisting strategy without using desensitization protocols.

Long-Term Outcomes after Conversion to a Belatacept-Based Immunosuppression in Kidney Transplant Recipients.

Conversion to a belatacept-based immunosuppression is currently used as a calcineurin inhibitor (CNI) avoidance strategy when the CNI-based standard-of-care immunosuppression is not tolerated after kidney transplantation. However, there is a lack of evidence on the long-term benefit and safety after conversion to belatacept. We prospectively enrolled 311 kidney transplant recipients from 2007 to 2020 from two referral centers, converted from CNI to belatacept after transplant according to a prespecified protocol. Patients were matched at the time of conversion to patients maintained with CNIs, using optimal matching. The primary end point was death-censored allograft survival at 7 years. The secondary end points were patient survival, eGFR, and safety outcomes, including serious viral infections, immune-related complications, antibody-mediated rejection, T-cell-mediated rejection, de novo anti-HLA donor-specific antibody, de novo diabetes, cardiovascular events, and oncologic complications. A total of 243 patients converted to belatacept (belatacept group) were matched to 243 patients maintained on CNIs (CNI control group). All recipient, transplant, functional, histologic, and immunologic parameters were well balanced between the two groups with a standardized mean difference below 0.05. At 7 years post-conversion to belatacept, allograft survival was 78% compared with 63% in the CNI control group ( P < 0.001 for log-rank test). The safety outcomes showed a similar rate of patient death (28% in the belatacept group versus 36% in the CNI control group), active antibody-mediated rejection (6% versus 7%), T-cell-mediated rejection (4% versus 4%), major adverse cardiovascular events, and cancer occurrence (9% versus 11%). A significantly higher rate of de novo proteinuria was observed in the belatacept group as compared with the CNI control group (37% versus 21%, P < 0.001). This real-world evidence study shows that conversion to belatacept post-transplant was associated with lower risk of graft failure and acceptable safety outcomes compared with patients maintained on CNIs. Long-term Outcomes after Conversion to Belatacept, NCT04733131 .

Myosteatosis is associated with poor survival after kidney transplantation: a large retrospective cohort validation.

We aim to establish diagnostic thresholds of sarcopenia and myosteatosis based on CT measurements, and to validate their prognostic value in a large cohort of kidney transplant recipients. Local healthy population with abdominal CT between 2010 and 2022, and patients underwent kidney transplantation between 2015 and 2019 at our center were retrospectively included. The skeletal muscle index and muscle attenuation of abdominal muscles were calculated based on CT image at the middle of the third lumbar vertebra. Primary endpoints included all-cause mortality and death censored allograft survival. Age- and sex-specific thresholds for sarcopenia and myosteatosis were established based on 1598 healthy local population. The final patient cohort consisted of 992 kidney transplant recipients (median age 34years, interquartile range 28-44years; 694 males), including 33 (3.3%) with sarcopenia and 95 (9.5%) with myosteatosis. Multivariate analysis revealed myosteatosis (adjusted hazard ratio = 3.08, p = 0.022) was an independent baseline risk factor of mortality after adjusting for age, the history of cancer, and the history of cardiovascular event. Multivariate analysis found preemptive transplantation (adjusted hazard ratio = 0.36, p = 0.037) was an independent protective factor of allograft loss. No difference was found in the prognosis between kidney transplant recipients with and without sarcopenia. Myosteatosis was an independent risk factor of mortality after kidney transplantation, but sarcopenia was not. Neither sarcopenia nor myosteatosis was associated with graft loss.

Association of Implantation Biopsy Findings in Living Donor Kidneys With Donor and Recipient Outcomes

Some living donor kidneys are found to have biopsy evidence of chronic scarring and/or glomerular disease at implantation, but it is unclear if these biopsy findings help predict donor kidney recovery or allograft outcomes. Our objective was to identify the prevalence of chronic histological changes and glomerular disease in donor kidneys, and their association with donor and recipient outcomes. Retrospective cohort study. Single center, living donor kidney transplants from January 2010 to July2022. Chronic histological changes, glomerular disease in donor kidney implantation biopsies. For donors, single-kidney estimated glomerular filtration rate (eGFR) increase, percent total eGFR loss,≥40% eGFR decline from predonation baseline, and eGFR<60mL/min/1.73m2 at 6 months after donation; for recipients, death-censored allograft survival. Biopsies were classified as having possible glomerular disease by pathologist diagnosis or chronic changes based on the percentage of glomerulosclerosis, interstitial fibrosis/tubular atrophy, and vascular disease. We used logistic regression to identify factors associated with the presence of chronic changes, linear regression to identify the association between chronic changes and single-kidney estimated glomerular filtration rate (eGFR) recovery, and time-to-event analyses to identify the relationship between abnormal biopsy findings and allograft outcomes. Among 1,104 living donor kidneys, 155 (14%) had advanced chronic changes on implantation biopsy, and 12 (1%) had findings suggestive of possible donor glomerular disease. Adjusted logistic regression showed that age (odds ratio [OR], 2.44 per 10 years [95% CI, 1.98-3.01), Hispanic ethnicity (OR, 1.87 [95% CI, 1.15-3.05), and hypertension (OR, 1.92 [95% CI, 1.01-3.64), were associated with higher odds of chronic changes on implantation biopsy. Adjusted linear regression showed no association of advanced chronic changes with single-kidney eGFR increase or relative risk of eGFR<60mL/min/1.73m2. There were no differences in time-to-death-censored allograft failure in unadjusted or adjusted Cox proportional hazards models when comparing kidneys with chronic changes to kidneys without histological abnormalities. Retrospective, absence of measured GFR. Approximately 1 in 7 living donor kidneys had chronic changes on implantation biopsy, primarily in the form of moderate vascular disease, and 1% had possible donor glomerular disease. Abnormal implantation biopsy findings were not significantly associated with 6-month donor eGFR outcomes or allograft survival. Kidney biopsies are the gold standard test to identify the presence or absence of kidney disease. However, kidneys donated by healthy living donors-who are extensively screened for any evidence of kidney disease before donation-occasionally show findings that might be considered "abnormal," including the presence of scarring in the kidney or findings suggestive of a primary kidney disease. We studied the frequency of abnormal kidney biopsy findings among living donors at our center. We found that about 14% of kidneys had chronic abnormalities and 1% had findings suggesting possible glomerular kidney disease, but the presence of abnormal biopsy findings was not associated with worse outcomes for the donors or their recipients.

#6395 TUBULORETICULAR INCLUSIONS: A NEW PROGNOSTIC BIOMARKER IN KIDNEY TRANSPLANTATION

Abstract Background and Aims Tubuloreticular inclusions (TRIs) seen on electron microscopy (EM) are classically associated with lupus nephritis (LN) and systemic viral infections in native biopsies. Traditionally a marker for enhanced type I interferon expression, little is known about their significance post-transplant. We aimed to look at a large cohort of transplant biopsies showing TRIs to investigate associations and outcomes. Method A retrospective analysis was performed on two prospective databases; an in-centre transplant registry and a histopathology database holding data on all kidney biopsies performed at our centre. All patients biopsied since 2015, who had EM examination were included. Where patients had more than one biopsy showing a TRI the earliest one was included. Demographic, clinical and transplant data was collected from the laboratory records. Results 2283 kidney transplant biopsies were performed between January 2015 and November 2022; 1898 (83.1%) had EM performed. Of 1898 with EM, 176 (10.8%) had evidence of TRIs. Of 176 patients, 34% were female, the median age was 52.2 (38.9-59.4) years, 32% had underlying glomerulonephritis as their cause of ESKD, 65% were deceased donors and 75% were of non-white ethnicity. TRIs were associated with serological evidence of autoimmunity (16%), viral infections (26%) and donor specific antibodies (28%), with no association found in 41%. Rejection occurred in 49%, including 31% of patients with no recognised association with TRIs. Allograft outcomes were poor, with all-cause allograft survival and death-censored allograft survival of 66% and 60%, after a follow up of 1.9 +/− 1.8 years post index biopsy. A comparison with a matched control group is planned Conclusion In extension to previous work, we show that TRIs appear to be associated with alloimmunity. In this regard they may be a useful biomarker especially in cases where the diagnosis is unclear or biopsy findings are ‘subthreshold’. Irrespective of aetiology, TRIs are associated with poor outcomes and warrant further consideration.

The UK kidney donor risk index poorly predicts long-term transplant survival in paediatric kidney transplant recipients.

The UK kidney offering scheme introduced a kidney donor risk index (UK-KDRI) to improve the utility of deceased-donor kidney allocations. The UK-KDRI was derived using adult donor and recipient data. We assessed this in a paediatric cohort from the UK transplant registry. We performed Cox survival analysis on first kidney-only deceased brain-dead transplants in paediatric (<18 years) recipients from 2000-2014. The primary outcome was death-censored allograft survival >30 days post-transplant. The main study variable was UK-KDRI derived from seven donor risk-factors, categorised into four groups (D1-low risk, D2, D3 and D4-highest risk). Follow-up ended on 31-December-2021. 319/908 patients experienced transplant loss with rejection as the main cause (55%). The majority of paediatric patients received donors from D1 donors (64%). There was an increase in D2-4 donors during the study period, whilst the level of HLA mismatching improved. The KDRI was not associated with allograft failure. In multi-variate analysis, increasing recipient age [adjusted HR and 95%CI: 1.05(1.03-1.08) per-year, p<0.001], recipient minority ethnic group [1.28(1.01-1.63), p<0.05), dialysis before transplant [1.38(1.04-1.81), p<0.005], donor height [0.99 (0.98-1.00) per centimetre, p<0.05] and level of HLA mismatch [Level 3: 1.92(1.19-3.11); Level 4: 2.40(1.26-4.58) versus Level 1, p<0.01] were associated with worse outcomes. Patients with Level 1 and 2 HLA mismatches (0 DR +0/1 B mismatch) had median graft survival >17 years regardless of UK-KDRI groups. Increasing donor age was marginally associated with worse allograft survival [1.01 (1.00-1.01) per year, p=0.05]. Adult donor risk scores were not associated with long-term allograft survival in paediatric patients. The level of HLA mismatch had the most profound effect on survival. Risk models based on adult data alone may not have the same validity for paediatric patients and therefore all age-groups should be included in future risk prediction models.

The comparative efficacy and safety of basiliximab and antithymocyte globulin in deceased donor kidney transplantation: a multicenter cohort study.

Generally, an induction agent is chosen based on the conditions of the deceased donor and the recipient. Antithymocyte globulin (ATG) is preferred in relatively high-risk conditions. No clear evidence indicates which induction agent is safer or more efficient for deceased donor kidney transplantation (DDKT). This study compares the efficacy and safety of basiliximab (BSX) and ATG according to donor characteristics in DDKT. A total of 724 kidney transplant recipients from three transplant centers were enrolled, and propensity score matching was performed. Based on a donor age of 60 years, donor kidney with acute kidney injury (AKI), and Kidney Donor Profile Index (KDPI) score of 65%, we investigated how the choice of induction therapy agent affected the posttransplant clinical outcomes of delayed graft function (DGF), acute rejection (AR), infectious complications, and allograft and patient survival. AR and DGF did not differ significantly according to induction agent in elderly/young donor, AKI/non-AKI, and high-KDPI/ low-KDPI subgroups. The infection rate did not show meaningful differences. The differences in death-censored allograft survival and patient survival rates between induction agents were not statistically significant. Our study suggests that BSX can produce clinical outcomes similarly favorable to those of ATG even in DDKT cases with relatively poor donor conditions. Nonetheless, the donor and recipient conditions, immunological risk, and infection risk must be all taken into consideration when choosing an induction agent. Therefore, clinicians should carefully select the induction therapy agent for DDKT based on the risks and benefits in each DDKT case.

Complications of rabbit anti-thymocyte globulin induction immunosuppression in HIV-infected kidney transplant recipients.

Kidney transplantation in HIV-infected individuals with end-stage kidney disease is associated with improved survival compared to dialysis. Rabbit anti-thymocyte globulin (rATG) induction in HIV-infected kidney transplant recipients has been associated with a lower risk of acute rejection, but data on the rates of de novo malignancy and BK viremia in these patients is lacking. We performed a single-center retrospective cohort study of adult HIV-infected individuals who underwent kidney transplantation with rATG induction between January 2006 and December 2016. The primary outcome was the development of de novo malignancy. Secondary outcomes included the development of BK viremia, infections requiring hospitalization, HIV progression, biopsy-proven acute rejection, and patient and allograft survival. Twenty-seven HIV-infected individuals with end-stage kidney disease received deceased (n=23) or living (n=4) donor kidney transplants. The cumulative rate of malignancy at five years was 29%, of whom 29% died because of advanced malignancy. BK viremia was detected in six participants (22%), of whom one had biopsy-proven BK virus-associated nephropathy and all of whom cleared the BK viremia. Five-year acute rejection rates, patient survival and death-censored allograft survival were 17%, 85% and 80% respectively. rATG induction in HIV-infected kidney transplant recipients was associated with a low risk of acute rejection, but a potentially higher risk of de novo malignancies and BK viremia in this cohort. Screening strategies to closely monitor for BK virus infection and malignancy post-transplantation may improve outcomes in HIV-infected kidney transplant recipients receiving rATG induction.

An interleukin 6-based genetic risk score strengthened with interleukin 10 polymorphisms associated with long-term kidney allograft outcomes

Of all kidney transplants, half are still lost in the first decade after transplantation. Here, using genetics, we probed whether interleukin 6 (IL-6) could be a target in kidney transplantation to improve graft survival. Additionally, we investigated if a genetic risk score (GRS) based on IL6 and IL10 variants could improve prognostication of graft loss. In a prospective cohort study, DNA of 1271 donor-recipient kidney transplant pairs was analyzed for the presence of IL6, IL6R, IL10, IL10RA, and IL10RB variants. These polymorphisms and their GRS were then associated with 15-year death-censored allograft survival. The C|C-genotype of the IL6 polymorphism in donor kidneys and the combined C|C-genotype in donor-recipient pairs were both associated with a reduced risk of graft loss (p=.043 and p=.042, respectively). Additionally, the GRS based on IL6, IL6R, IL10, IL10RA, and IL10RB variants was independently associated with the risk of graft loss (HR 1.53, 95%-CI [1.32-1.84]; p<.001). Notably, the GRS improved risk stratification and prediction of graft loss beyond the level of contemporary clinical markers. Our findings reveal the merits of a polygenic IL-6-based risk score strengthened with IL-10- polymorphisms for the prognostication and risk stratification of late graft failure in kidney transplantation.

401.5: Development of High-Performing and Multicenter-Validated Dynamic Prediction Models With Longitudinal Measurements of Serum Creatinine and Proteinuria for Death-Censored Kidney Graft Failure

Introduction: Prediction models of graft survival in kidney transplantation allow risk stratification of kidney transplant recipients using big data and artificial intelligence. Many models require detailed information on allograft histology and presence of donor-specific antibodies which are not readily available in every transplant center. We developed a joint model using Bayesian estimation to correlate baseline transplant characteristics and longitudinal measurements of both serum creatinine (S-Cr) and urine protein-creatinine ratios (u-PCR) with death-censored graft failure (DCGF). Methods: 3596 kidney transplant recipients (KTRs) from four transplant centers in Europe were included with a total of 452.033 S-Cr and u-PCR measurements. Each KTR had a median of 112 (IQR: 52-163) consecutive measurements. The interval between measurements was 7 (IQR: 1-35) days. Median follow-up was 6 (IQR: 3-9) years. Model predictors included recipient and donor gender and age, total number of human leukocyte antigen-mismatches, donor type, pre-transplant DSAs, and dialysis vintage. Primary outcomes were DCGF six months after last S-Cr or u-PCR measurement and DCGF seven years post-transplantation. Two training and external validation methods have been used to assess best model performance: model 1; development in one center and validation in three remaining centers, and model 2; development on 80% of the total cohort and validation on the remaining 20% (Table 1). Results: A total of 549 (15%) out of 3596 KTRs experienced DCGF. Joint modeling revealed that recipient age, recipient gender, donor age, transplantation after dialysis initiation, and serial measurements of S-Cr and u-PCR were independent risk factors for DCGF. Our final joint models showed good calibration (prediction error: 0.01) and very high discrimination in the development and validation cohorts (6-months incident AUC 0.9 [95% CI: 0.87-0.93] and 7-years dynamic AUC 0.84 [95% CI: 0.81-0.87] for model 1, and 6-months incident AUC 0.98 [95% CI: 0.96-1.00] and 7-years dynamic AUC 0.85 [95% CI: 0.80-0.91] for model 2) (Table 1). Especially model 2 could be of interest as a personalized surveillance tool in clinical practice given its AUCs >0.95 from year 1 onwards.Conclusion: We developed a high performing and multicenter-validated, dynamic prediction model on death-censored allograft survival based on traditionally available baseline transplant characteristics and longitudinal measurements of S-Cr and u-PCR. This dynamic model can continuously be updated with new measurements and might enable personalized surveillance of kidney transplant recipients and objectify allograft prognosis (as illustrated in Figure 1). Of notice, our models can be extended with newly discovered dynamic biomarkers in the future if needed.

Successful ABO and HLA incompatible kidney transplantation in children in the UK

BackgroundThere is increasing evidence of good short-term and medium-term outcomes of ABO incompatible (ABOi) and HLA incompatible (HLAi) kidney transplantation with pre-transplant positive crossmatches in paediatric practice. However, there remain concerns regarding the higher risks of infective complications and antibody-mediated rejections. The aim of our study is to show longer-term follow-up on all ABOi and HLAi paediatric kidney transplant recipients (pKTR) in the UK.MethodsQuestionnaires specifying kidney transplant type, desensitisation requirement and kidney allograft function were sent to 13 paediatric nephrology centres that performed kidney transplantation in children and young people under 18 years of age who received an ABOi and/or HLAi transplant between 1 January 2006 and 31 December 2016. Patient and kidney allograft survival were compared between ABOi, HLAi and ABO/HLA compatible (ABOc/HLAc) groups.ResultsAmong 711 living donor kidney transplants performed in the UK, 23 were ABOi and 6 were HLAi. Patient survival was 87%, 100% and 96% in ABOi, HLAi and ABOc/HLAc groups, respectively, at median follow-up of 6.8 (3.6–14.0) years post-transplant. Death-censored kidney allograft survival was 100% in all 3 groups at last follow-up. There were no cases of primary non-function in ABOi or HLAi groups, but 2% in the ABOc/HLAc group. There was one reported case of Epstein-Barr viral-induced post-transplant lymphoproliferative disorder.ConclusionLonger term follow-up has shown that ABOi and HLAi kidney transplantation are feasible for pKTR where no compatible donors are available, and that minimising desensitisation should be achieved where possible.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information.

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.

Risk factors for renal allograft survival with China novel donation category: Donation after brain death followed by cardiac arrest

IntroductionTo meet the need for transplantable organs, a new donation program was initiated by the Chinese government. This novel policy created three categories for deceased organ donations: donation after circulatory death cardiac death (DCD), donation after brain death (DBD), and donation after brain death followed by circulatory death (DBCD) meaning complete cardiac arrest. In fact, the DBCD method is a combination of both DBD and DCD methods. A DBCD donor meets the criteria of for brain death, but the organ procurement begins after the withdrawal of life support and the subsequent cardiac arrest death. The purpose of this study was to evaluate the long-term outcomes of kidney transplantation in our center with the DBCD policy. Potential risk factors for affecting the renal allograft survival were also analyzed based on our data. MethodA retrospective study, involving 421 kidney transplants derived from 214 donors, was conducted between December 2011 and October 2019. In particular, 373 (88.6%) transplanted organs met the criteria for DBCD, and 48 (11.4%) for DCD. The log-rank test was used to compare the difference in survival. The Cox regression analysis was used for risk factor screening. ResultAnalysis showed that the DBCD group was better than the DCD group in terms of overall (p = 0.031) as well as death-censored (p = 0.026) allograft survival using the log-rank test. A Cox regression analysis revealed that increasing donor age (p = 0.002, HR = 1.820/10 years incremental older), increasing recipient age (p = 0.028, HR = 1.521/10 years increment older), prolonged dialysis duration (p = 0.007, HR = 1.018), occurrence episodes of acute rejection (p = 0.016, HR = 2.697), delayed graft function (p = 0.012, HR = 2.962), mismatch ≥4 HLA loci (p = 0.038, HR = 3.606), and warm ischemia time > 15 min (p = 0.022, HR = 2.915), were all independent risk factors affecting the graft survival. ConclusionThe new DBCD policy of donation produced acceptable results similar or even better than the DCD practice. Based on our analysis, the graft survival of DBCD transplants may be better than DCD transplants. The main risk factors for allograft loss included an increasing donor age, recipient age, warm ischemia time > 15 min, prolonged dialysis duration, acute rejection, delayed graft function, and HLA mismatch ≥4 HLA loci.

Japanese Single-Center Experience of Kidney Transplant: Experience in a Japanese Private Hospital

We reviewed the results of cases of kidney transplant (KTx) that were conducted at the Toda Chuo General Hospital, a private hospital located in Saitama, Japan. A total of 312 patients with end-stage renal failure underwent KTx between January 1992 and December 2019 at Toda Chuo General Hospital. There were 191 men and 121 women. Their mean age was 45.7 years. Of the 312 cases, 310 were living-related KTx, while 2 were deceased donor KTx. The immunosuppressive treatment protocol mainly consisted of 4-drug therapy with methylprednisolone, tacrolimus, mycophenolate mofetil, and basiliximab. Patient survival was 99.7% at 1 year, 99.3% at 5 years, and 97.3% at 10 years. Renal allograft survival was 98.4% at 1 year, 91.7% at 5 years, and 86.5% at 10 years. However, death-censored renal allograft survival was 98.7% at 1 year, 92.4% at 5 years, and 89.0% at 10 years. Among the 312 patients, 33 grafts were lost during the observation period. The loss was because of chronic antibody-mediated rejection in 19 patients, death with function in 6 patients, and acute antibody-mediated rejection in 2 patients. The prognosis of patients and their grafts, which were managed following the immunosuppression protocol at our institute, was relatively good. KTx in a private hospital in Japan is at par with the global standard.

Recipient APOL1 risk alleles associate with death-censored renal allograft survival and rejection episodes.

Apolipoprotein L1 (APOL1) risk alleles in donor kidneys associate with graft loss, but whether recipient risk allele expression affects transplant outcomes is unclear. To test whether recipient APOL1 risk alleles independently correlate with transplant outcomes, we analyzed genome-wide SNP genotyping data on donors and recipients from 2 kidney transplant cohorts: Genomics of Chronic Allograft Rejection (GOCAR) and Clinical Trials in Organ Transplantation 01/17 (CTOT-01/17). We estimated genetic ancestry (quantified as the proportion of African ancestry, or pAFR) by ADMIXTURE and correlated APOL1 genotypes and pAFR with outcomes. In the GOCAR discovery set, we noted that the number of recipient APOL1 G1/G2 alleles (R-nAPOL1) associated with an increased risk of death-censored allograft loss (DCAL), independent of ancestry (HR = 2.14; P = 0.006), as well as within the subgroup of African American and Hispanic (AA/H) recipients (HR = 2.36; P = 0.003). R-nAPOL1 also associated with an increased risk of any T cell-mediated rejection (TCMR) event. These associations were validated in CTOT-01/17. Ex vivo studies of PMBCs revealed, unexpectedly, high expression levels of APOL1 in activated CD4+/CD8+ T cells and NK cells. We detected enriched immune response gene pathways in risk allele carriers compared with noncarriers on the kidney transplant waitlist and among healthy controls. Our findings demonstrate an immunomodulatory role for recipient APOL1 risk alleles associated with TCMR and DCAL. We believe this finding has broader implications for immune-mediated injury to native kidneys.

Increased Levels of sCD30 Have No Impact on the Incidence of Early ABMR and Long-Term Outcome in Intermediate-Risk Renal Transplant Patients With Preformed DSA.

Background: It is still incompletely understood why some patients with preformed donor-specific anti-HLA antibodies (DSA) have reduced kidney allograft survival secondary to antibody-mediated rejection (ABMR), whereas many DSA-positive patients have favorable long-term outcomes. Elevated levels of soluble CD30 (sCD30) have emerged as a promising biomarker indicating deleterious T-cell help in conjunction with DSA in immunologically high-risk patients. We hypothesized that this would also be true in intermediate-risk patients.Methods: We retrospectively analyzed pre-transplant sera from 287 CDC-crossmatch negative patients treated with basiliximab induction and tacrolimus-based maintenance therapy for the presence of DSA and sCD30. The incidence of ABMR according to the Banff 2019 classification and death-censored allograft survival were determined.Results: During a median follow-up of 7.4 years, allograft survival was significantly lower in DSA-positive as compared to DSA-negative patients (p < 0.001). In DSA-positive patients, most pronounced in those with strong DSA (MFI > 5,000), increased levels of sCD30 were associated with accelerated graft loss compared to patients with low sCD30 (3-year allograft survival 75 vs. 95%). Long-term survival, however, was comparable in DSA-positive patients irrespective of sCD30 status. Likewise, the incidence of early ABMR and lesion score characteristics were comparable between sCD30-positive and sCD30-negative patients with DSA. Finally, increased sCD30 levels were not predictive for early persistence of DSA.Conclusion: Preformed DSA are associated with an increased risk for ABMR and long-term graft loss independent of sCD30 levels in intermediate-risk kidney transplant patients.

Pre-transplant donor-specific HLA antibodies and risk for poor first-year renal transplant outcomes: results from the Swiss Transplant Cohort Study.

The aim of this study was to analyze first year renal outcomes in a nationwide prospective multicenter cohort comprising 2215 renal transplants, with a special emphasis on the presence of pre-transplant donor-specific HLA antibodies (DSA). All transplants had a complete virtual crossmatch and DSA were detected in 19% (411/2215). The investigated composite endpoint was a poor first-year outcome defined as (i) allograft failure or (ii) death or (iii) poor allograft function (eGFR ≤25ml/min/1.73m2 ) at one year. Two hundred and twenty-one (221/2215; 10%) transplants showed a poor first-year outcome. Rejection (24/70; 34%) was the most common reason for graft failure. First-year patient's death was rare (48/2215; 2%). There were no statistically significant differences between DSA-positive and DSA-negative transplants regarding composite and each individual endpoint, as well as reasons for graft failure and death. DSA-positive transplants experienced more frequently rejection episodes, mainly antibody-mediated rejection (both P<0.0001). The combination of DSA and any first year rejection was associated with the overall poorest death-censored allograft survival (P<0.0001). In conclusion, presence of pre-transplant DSA per se does not affect first year outcomes. However, DSA-positive transplants experiencing first year rejection are a high-risk population for poor allograft survival and may benefit from intense clinical surveillance.

Application of the iBox prognostication system as a surrogate endpoint in the TRANSFORM randomised controlled trial: proof-of-concept study

ObjectivesDevelopment of pharmaceutical agents in transplantation is currently limited by long waits for hard endpoints. We applied a validated integrative risk-prognostication system integrative Box (iBox) as a surrogate endpoint to...

Functional Fc Gamma Receptor Gene Polymorphisms and Long-Term Kidney Allograft Survival

The functional Fc gamma receptor (FcγR) IIIA polymorphism FCGR3A-V/F158 was earlier suggested to determine the potential of donor-specific HLA antibodies to trigger microcirculation inflammation, a key lesion of antibody-mediated renal allograft rejection. Associations with long-term transplant outcomes, however, have not been evaluated to date. To clarify the impact of FCGR3A-V/F158 polymorphism on kidney transplant survival, we genotyped a cohort of 1,940 recipient/donor pairs. Analyzing 10-year death-censored allograft survival, we found no significant differences in relation to FCGR3A-V/F158. There was also no independent survival effect in a multivariable Cox model. Similarly, functional polymorphisms in two other activating FcγR, FCGR2A-H/R131 (FcγRIIA) and FCGR3B-NA1/NA2 (FcγRIIIB), were not associated with outcome. There were also no significant survival differences among patient subgroups at increased risk of rejection-related injury, such as pre-sensitized recipients (> 0% panel reactivity; n = 438) or recipients treated for rejection within the first year after transplantation (n = 229). Our study results suggest that the earlier shown association of FcγR polymorphism with microcirculation inflammation may not be strong enough to exert a meaningful effect on graft survival.