Living Donor Kidney Transplant Recipients Research Articles

Long-Term Outcomes of Kidney Paired Donation Transplantation: A Single Center Retrospective Cohort Study

This study aimed to compare the kidney paired donation (KPD) program recipients with the traditional living donor kidney transplantation (LDKT) recipients regarding patient and graft survival. We retrospectively analyzed 141 recipients of the KPD program and 141 classic LDKT recipients that we matched for age and sex as controls between July 2005 and June 2019. We compared the 2 transplant groups for patient and kidney survival using the Kaplan-Maier test. We also performed Cox Regression analysis to examine factors affecting patient survival, including transplant type. The average follow-up period was 96.17 ± 44.22 months. Of the 282 patients, 88 died in the follow-up period. There was no statistically significant difference in graft and patient survival between the KPD and LDKT groups. In the Cox regression model, including the transplant type, only the serum creatinine level measured in the first month after discharge was a significant factor in predicting patient survival. The findings of this study indicate that the KPD program is an effective and reliable method to increase LDKT. Country-wide multicentric studies should confirm the results of this study. In countries where cadaver transplantation is insufficient, efforts should be made to expand the KPD program.

Impact of Low-Level Donor-Specific Anti-HLA Antibody on Posttransplant Clinical Outcomes in Kidney Transplant Recipients.

The clinical significance of low-level donor-specific anti-HLA antibody (low-DSA) remains controversial. We investigated the impact of low-DSA on posttransplant clinical outcomes in kidney transplant (KT) recipients. We retrospectively reviewed 1,027 KT recipients, namely, 629 living donor KT (LDKT) recipients and 398 deceased donor KT (DDKT) recipients, in Seoul St. Mary's Hospital (Seoul, Korea) between 2010 and 2018. Low-DSA was defined as a positive anti-HLA-DSA result in the Luminex single antigen assay (LABScreen single antigen HLA class I - combi and class II - group 1 kits; One Lambda, Canoga Park, CA, USA) but a negative result in a crossmatch test. We compared the incidence of biopsy-proven allograft rejection (BPAR), changes in allograft function, allograft survival, patient survival, and posttransplant infections between subgroups according to pretransplant low-DSA. The incidence of overall BPAR and T cell-mediated rejection did not differ between the subgroups. However, antibody-mediated rejection (ABMR) developed more frequently in patients with low-DSA than in those without low-DSA in the total cohort and the LDKT and DDKT subgroups. In multivariate analysis, low-DSA was identified as a risk factor for ABMR development. Its impact was more pronounced in DDKT (odds ratio [OR]: 9.60, 95% confidence interval [CI]: 1.79-51.56) than in LDKT (OR: 3.76, 95% CI: 0.99-14.26) recipients. There were no significant differences in other outcomes according to pretransplant low-DSA. Pretransplant low-DSA has a significant impact on the development of ABMR, and more so in DDKT recipients than in LDKT recipients, but not on long-term outcomes.

Protection From Second Warm Ischemic Injury Using a Thermal Barrier Bag in Kidney Transplantation.

A living-donor nephrectomy was performed using a minimum skin incision procedure. After back table preparation, the kidney graft was placed inside the TBB and preserved during vascular anastomosis. The graft surface temperature was measured before and after vascular anastomosis using a noncontact infrared thermometer. After completion of the anastomosis, the TBB was removed from the transplanted kidney before graft reperfusion. Clinical data, including patient characteristics and perioperative variables, were collected. The primary endpoint was safety, which was assessed by evaluating adverse events. The secondary endpoints were the feasibility, tolerability, and efficacy of the TBB in kidney transplant recipients. Ten living-donor kidney transplant recipients with a median age of 56 y (range, 39-69 y) were enrolled in this study. No serious adverse events related to the TBB were observed. The median second warm ischemic time was 31 (27-39) min, and the median graft surface temperature at the end of anastomosis was 16.1 °C (12.8-18.7 °C). TBB can maintain transplanted kidneys at a low temperature during vascular anastomosis, which contributes to the functional preservation of transplanted kidneys and stable transplant outcomes.

Long-term prolonged-release tacrolimus outcomes in living donor kidney transplantation: The Japan Academic Consortium of Kidney Transplantation study-II.

To evaluate the 10-year efficacy and safety of a prolonged-release tacrolimus-based combination immunosuppressive regimen on longer-term outcomes in living donor kidney transplantation. Data from Japanese living donor kidney transplant recipients (n= 410) maintained on continuous prolonged-release tacrolimus-based immunosuppression from 2009-2013 were analyzed with a median follow-up of 9.9 years. A prolonged-release, tacrolimus-based combination regimen provided death-censored graft failure and all-cause death rates at 10 years of 7.0% and 6.8%, respectively. In multivariable analyses, acute and chronic rejection and 'throughout' (new-onset plus preexisting) diabetes mellitus were risk factors for death-censored graft failure. Recipient age ≥ 65 years, throughout diabetes mellitus and malignancy were common risk factors for all-cause death. Throughout diabetes mellitus was the most common risk factor for both death-censored graft failure and all-cause death. Additional analyses showed 10-year cumulative rates of death-censored graft failure were 14.0% and 5.4% for recipients with or without preexisting diabetes mellitus, respectively (log-rank test: p= 0.009). All-cause death rates were 12.7% and 5.4% in the preexisting and non-diabetes mellitus groups, respectively (log-rank test: p= 0.023). In this real-world, retrospective, living donor kidney transplantation study, a prolonged-release tacrolimus-based immunosuppressive combination regimen provided 10-year death-censored graft failure rates of 14.0% and 5.4% in diabetes mellitus and non-diabetes mellitus patients, respectively; Similarly, 10-year all-cause death rates were 12.7% and 5.4% in diabetes mellitus and non-diabetes mellitus patients, respectively. To our knowledge, the data in this study are the first to provide 10-year transplant outcomes in living donor kidney transplant recipients under prolonged-release tacrolimus-based regimen.

563 - A Randomized, Controlled, Multicenter, Safety and Efficacy Study of FCR001 Cell-Based Therapy Relative to a Tacrolimus- and Mycophenolate-Based Regimen in De Novo Living-Donor Kidney Transplant Recipients, and Safety in FCR001 Donors (FREEDOM-1 study)

563 - A Randomized, Controlled, Multicenter, Safety and Efficacy Study of FCR001 Cell-Based Therapy Relative to a Tacrolimus- and Mycophenolate-Based Regimen in De Novo Living-Donor Kidney Transplant Recipients, and Safety in FCR001 Donors (FREEDOM-1 study)

A Single-Center Experience With Kidney Transplantation in Patients Who Had Low Left Ventricular Ejection Fraction.

Left ventricular hypertrophy is one of the most typical cardiac abnormalities detected in patients with end-stage renal disease. In patients with congestive heart failure, the most crucial factor determining patient survival is left ventricular ejection fraction. Herein, we present our experience with living donor kidney transplant recipients with a left ventricular ejection fraction of <50%. Patients who underwent living donor kidney transplant in our center between November 2008 and November 2021 and had pretransplant left ventricular ejection fraction <50% were included. All patients had dialysis the day before surgery. All patients underwent 2-dimensional echocardiograms after dialysis and were categorized according to New York Heart Association classification, pretransplant and on posttransplant day 5. Demographic parameters and additional data, including pretransplant and posttransplant day 5 New York Heart Association classification, left ventricular ejection fraction at 6 months, and graft survival at 6 months, as well as patient survival data, were analyzed. Our study included 31 patients (mean age of 46.6 ± 18.3; range, 11-77 years). We found significant differences in New York Heart Association classifications before and after transplant, indicating that kidney transplant had a positive effect on pretransplant congestive heart failure in patients with low left ventricular ejection fraction (P = .001). The mean pretransplant left ventricular ejection fraction was 32 ± 9.9% (range, 1%-45%), whereas the mean 6-month posttransplant left ventricular ejection fraction was 52 ± 8.7% (range, 28%-63%) (P < .001). Both graft loss and all-cause mortality rates were 12.9%. Low left ventricular ejection fraction is not a contraindication for kidney transplant. We suggest that myocardial scintigraphy should be performed in patients with end-stage renal disease and low left ventricular ejection fraction, and kidney transplant should be considered in those without ischemic findings.

The detrimental effect of donor-specific antibodies is irrespective of its level in highly-immunized living donor kidney transplant recipients: A case-control series.

The impact of donor-specific antibodies (DSA) in (highly-) immunized living donor kidney transplant recipients is reported differentially in various patient cohorts. We have performed a retrospective analysis of all consecutive HLA-incompatible living donor kidney transplant recipients in our center between 2010-2019. Recipients who underwent plasmafiltration for a positive CDC-crossmatch were excluded. For each DSA+ recipient (DSA+), one immunized recipient without DSA (pPRA+) and two non-immunized recipients (pPRA-) were included. Patient and graft survival were analyzed and a subgroup analysis of DSA+ recipients was performed. For 63 DSA+ recipients, 63 PRA+ and 126 PRA- recipients were included. 26 (41%) had class I, 24 (38%) class II and 13 (21%) combined HLA class I and II DSA. Death-censored graft survival was inferior in DSA+ recipients compared to pPRA+ (HR 2.38 [95% CI 1.00-5.70]) as well as to pPRA- (HR 3.91 [1.86-8.22]). In multivariate analysis, DSA remained of negative influence on death-censored graft survival. Flowcytometric crossmatch, MFI value, HLA class and origin of DSA were not of significant impact. In our cohort of (highly-) immunized recipients, pretransplant DSA led to inferior death-censored graft survival. There were no "safe" DSA characteristics since only DSA per se impacted death-censored graft survival.

Low Incidence of Acute Antibody-Mediated Rejection after HLA Desensitization in Living Donor Kidney Transplant Recipients.

Desensitization allows the performance of human leukocyte antigen (HLA)-incompatible transplants. However, the incidence of acute rejection (AR) is high. This study aims to analyze the incidence of AR after transplantation with HLA-incompatible living donors in patients who underwent desensitization. Patients were immunosuppressed with tacrolimus, mycophenolic acid derivatives, and steroids after being desensitized with rituximab, plasma exchange, and/or immunoadsorption with specific cytomegalovirus immunoglobulins. A negative complement-dependent cytotoxicity or flow cytometry crossmatch and a donor-specific antibody titer < 1000 mean fluorescence intensity (MFI) were used to determine desensitization efficacy. A total of 36 patients underwent desensitization, and 27 (75%) were transplanted. After a follow-up of 58 ± 58 months (Min−Max: 0.13−169.5), five episodes of AR occurred: two antibody-mediated and three T-cell-mediated. No differences were found in baseline calculated panel-reactive antibodies (cPRA), class I or II MFI, number of antibodies, or Relative Intensity Scale (RIS) between AR and non-AR patients. Patients with antibody-mediated AR had higher cPRA (NS), MFI class I (p = 0.07) and class II (p = 0.006), and RIS (p = 0.01). The two patients with antibody-mediated AR and one patient with T-cell-mediated AR lost their grafts. In conclusion, the incidence of acute antibody-mediated rejection after desensitization was 7.4%, which occurred early post-transplantation in patients with high MFI and was associated with early graft loss.

Role of gender mismatch on outcomes of living donor kidney transplant recipient: a 5-year retrospective study

Role of gender mismatch on outcomes of living donor kidney transplant recipient: a 5-year retrospective study

Delayed graft function in pediatric living donor kidney transplantation.

Pediatric recipients of living donor kidneys have a low rate of delayed graft function (DGF). We examined the incidence, risk factors and outcomes of DGF in pediatric patients who received a living donor allograft. The STARfile was queried to examine all pediatric patients transplanted with a living donor kidney between 2000 and 2020. Donor and recipient demographic data were examined, as were survival and outcomes. Recipients were stratified into DGF and no DGF groups. DGF was defined as the need for dialysis within the first week after transplant. 6480 pediatric patients received a living donor (LD) kidney transplant during the study period. 269 (4.2%) developed DGF post-transplant. Donors were similar in age, creatinine, and cold ischemia time. Recipients of kidneys with DGF were similar in age, sensitization status and HLA mismatch. Focal segmental glomerulosclerosis (FSGS) was the most common diagnosis in recipients with DGF, and allograft thrombosis was the most common cause of graft loss in this group. Small recipients (weight < 15 kg) were found to have a significantly higher rate of DGF. Length of stay doubled in recipients with DGF, and rejection rates were higher post-transplant. Recipients of LD kidneys who developed DGF had significantly worse 1 year allograft survival (67% vs. 98%, p< .0001). Pediatric living donor kidney transplant recipients who experience DGF have significantly poorer allograft survival. Optimizing the donor and recipient matching to avoid compounding risks may allow for better outcomes.

Influence of Graft Ureter Length, a Donor-Related Factor, on Urinary Tract Infections After Living-Donor Kidney Transplantation: A Single-Center Analysis of 211 Cases.

Urinary tract infection (UTI) occurs in 25% of recipients of living-donor kidney transplantation (LDKT). Female sex, age, and anatomical abnormalities have been reported as recipient-related risk factors for UTI after LDKT; few studies have reported donor-related factors. We retrospectively examined UTI occurrence within 5years of transplantation in recipients (n = 211) who underwent LDKT at our hospital between April 2011 and April 2021. All nephrectomies were performed using a retroperitoneal pure laparoscopic approach. The ureter was dissected at the lower level of the common iliac artery and trimmed to the shortest length, enough to reach the bladder using extra vesicular ureterocystoneostomy with a 3cm submucosal tunnel. Twenty-nine recipients (13.7%) developed UTI within 5years, and the median time to onset was 40.0days. After adjusting for the well-known factors, including recipient sex, graft ureter length was an independent factor for UTI occurrence (HR 1.25, 95% CI 1.02∼1.53, p = 0.028) in the multivariate Cox regression analysis. The long ureter is usually trimmed, and the widest part is used for anastomosis, which may increase the possibility of reflux from the bladder to the ureter in the standard technique. The ureter length may be associated with the incidence of UTI after LDKT.

Individualised immunosuppression with intravenously administered donor-derived modified immune cells compared with standard of care in living donor kidney transplantation (TOL-2 Study): protocol for a multicentre, open-label, phase II, randomised controlled trial

IntroductionDonor-derived modified immune cells (MIC) induced long-term specific immunosuppression against the allogeneic donor in preclinical models of transplantation. In a phase I clinical trial (TOL-1 Study), MIC treatment resulted in...

Effect of pretransplant dialysis vintage on clinical outcomes in deceased donor kidney transplant

The waiting time for deceased donor kidney transplants (DDKT) is increasing. We evaluated DDKT prognosis according to the pretransplant dialysis vintage. A total of 4117 first-time kidney transplant recipients were enrolled from a prospective nationwide cohort in Korea. DDKT recipients were divided into tertiles according to pretransplant dialysis duration. Graft failure, mortality, and composite were compared between DDKT and living donor kidney transplant (LDKT) recipients. Pretransplant dialysis vintage was longer annually in DDKT recipients. In the subdistribution of the hazard model for the competing risk, the first tertile did not show an increased risk of graft failure compared with LDKT recipients; however, the second and third tertile groups had an increased risk of graft failure compared to LDKT recipients (adjusted hazard ratio [aHR] 3.59; 95% confidence interval [CI] 1.69–7.63; P < 0.001; aHR 2.37; 95% CI 1.06–5.33; P = 0.037). All DDKT groups showed a significantly higher risk of patient death than LDKT, with the highest risk in the third tertile group (aHR 11.12; 95% CI 4.94–25.00; P < 0.001). A longer pretransplant dialysis period was associated with a higher risk of the composite of patient death and graft failure in DDKT recipients. DDKT after a short period of dialysis had non-inferior results on graft survival compared with LDKT.

Patient and Graft Survival After A1/A2-incompatible Living Donor Kidney Transplantation.

Background.ABO type B and O kidney transplant candidates have increased difficulty identifying a compatible donor for living donor kidney transplantation (LDKT) and are harder to match in kidney paired donation registries. A2-incompatible (A2i) LDKT increases access to LDKT for these patients. To better inform living donor selection, we evaluated the association between A2i LDKT and patient and graft survival.Methods.We used weighted Cox regression to compare mortality, death-censored graft failure, and all-cause graft loss in A2i versus ABO-compatible (ABOc) recipients.Results.Using Scientific Registry of Transplant Recipients data 2000–2019, we identified 345 A2i LDKT recipients. Mortality was comparable among A2i and ABOc recipients; weighted 1-/5-/10-y mortality was 0.9%/6.5%/24.2%, respectively, among A2i LDKT recipients versus 1.4%/7.7%/22.2%, respectively, among ABOc LDKT recipients (weighted hazard ratio [wHR], 0.811.041.33; P = 0.8). However, A2i recipients faced higher risk of death-censored graft failure; weighted 1-/5-/10-y graft failure was 5.7%/11.6%/22.4% for A2i versus 1.7%/7.5%/17.2% for ABOc recipients (wHR in year 1 = 2.243.565.66; through year 5 = 1.251.782.53; through year 10 = 1.151.552.07). By comparison, 1-/5-/10-y wHRs for A1-incompatible recipients were 0.631.966.08/0.390.942.27/0.390.831.74.Conclusions.A2i LDKT is generally safe, but A2i donor/recipient pairs should be counseled about the increased risk of graft failure and be monitored as closely as their A1-incompatible counterparts posttransplant.

Pain Interference in End Stage Kidney Disease is Associated with Changes in Gut Microbiome Features Before and After Kidney Transplantation

BackgroundPain, a common debilitating symptom among kidney transplant recipients (KTRs), is among the most common and undertreated symptoms after kidney transplantation. AimsCharacterize associations between gut microbiome features and pain interference before and after kidney transplantation. DesignLongitudinal, repeated measures study, collecting fecal specimens and pain interference data pretransplant and 3 months posttransplant. SettingParticipants were recruited at the kidney transplant clinic at the University of Illinois Hospital & Health Sciences System. Participants/subjects19 living donor kidney transplant recipients. MethodsWe assessed fecal microbial community structure with shotgun metagenomic sequencing; we used pain interference scores derived from the Patient-Reported Outcomes Measurement Information System-57. ResultsWe measured a reduction in the Shannon diversity index in both groups after transplantation but observed no significant differences between groups at either time point. We did observe significant differences in fecal microbial Bray-Curtis similarity index among those reporting pain interference pre- transplant versus no pain interference at 3-months posttransplant (R = .306, p = .022), and between pain interference groups at posttransplant (R = .249, p = .041). Pairwise models showed significant differences between groups posttransplant in relative abundances of several taxa, including a 5-fold reduction.ßin Akkermansia among those with pain interference and a higher relative abundance of taxa associated with chronic inflammation in those with pain interference posttransplant. Functional gene analysis identified two features that were significantly enriched in those with pain interference, including a peptide transport system gene. ConclusionsGut microbiota community structure differs between groups with and without pain interference at 3 months after kidney transplantation. Several taxa involved in intestinal barrier integrity and chronic inflammation were associated with posttransplant pain.

Induction of Long-Lasting Regulatory B Lymphocytes by Modified Immune Cells in Kidney Transplant Recipients.

We recently demonstrated that donor-derived modified immune cells (MICs)-PBMCs that acquire immunosuppressive properties after a brief treatment-induced specific immunosuppression against the allogeneic donor when administered before kidney transplantation. We found up to a 68-fold increase in CD19 + CD24 hi CD38 hi transitional B lymphocytes compared with transplanted controls. Ten patients from a phase 1 clinical trial who had received MIC infusions before kidney transplantation were followed to post-transplant day 1080. Patients treated with MICs had a favorable clinical course, showing no donor-specific human leukocyte antigen antibodies or acute rejections. The four patients who had received the highest dose of MICs 7 days before surgery and were on reduced immunosuppressive therapy showed an absence of in vitro lymphocyte reactivity against stimulatory donor blood cells, whereas reactivity against third party cells was preserved. In these patients, numbers of transitional B lymphocytes were 75-fold and seven-fold higher than in 12 long-term survivors on minimal immunosuppression and four operationally tolerant patients, respectively ( P <0.001 for both). In addition, we found significantly higher numbers of other regulatory B lymphocyte subsets and a gene expression signature suggestive of operational tolerance in three of four patients. In MIC-treated patients, in vitro lymphocyte reactivity against donor blood cells was restored after B lymphocyte depletion, suggesting a direct pathophysiologic role of regulatory B lymphocytes in donor-specific unresponsiveness. These results indicate that donor-specific immunosuppression after MIC infusion is long-lasting and associated with a striking increase in regulatory B lymphocytes. Donor-derived MICs appear to be an immunoregulatory cell population that when administered to recipients before transplantation, may exert a beneficial effect on kidney transplants. MIC Cell Therapy for Individualized Immunosuppression in Living Donor Kidney Transplant Recipients (TOL-1), NCT02560220.

423.2: Patient and Graft Survival After A1/A2-Incompatible Living Donor Kidney Transplantation

Background: ABO type B and O kidney transplant candidates often have increased difficulty identifying a compatible donor for living donor kidney transplantation (LDKT) and are harder to match in kidney paired donation (KPD) registries. A2-incompatible (A2i) LDKT increases access to LDKT for these patients. Kidney transplantation across the A2 barrier (A2 -> O, A2 -> B, A2B -> B) is believed to be safer than that across the A1 barrier (A1 -> O, A1 -> B, A1B -> B) because A2 kidneys express fewer A antigens on their renal endothelial surfaces. However, the differential risk of A2i LDKT and its relative benefit when compared to A1-incompatible (A1i) LDKT, if any, remains unknown. To better inform living donor selection, we evaluated the association between A2i LDKT and patient and graft survival. Methods: We used inverse probability weighted Cox regression to compare mortality, death-censored graft failure, and all-cause graft loss in A2i vs. ABO-compatible (ABOc) recipients. These methods were repeated to compare mortality, death-censored graft failure, and all-cause graft loss between A1i vs. comparable ABOc LDKT recipients. Results: Using data from the Scientific Registry of Transplant Recipients (SRTR) 2000-2019, we identified 345 A2i LDKT recipients. Mortality was comparable among A2i and ABOc recipients; weighted 1/5/10-year mortality was 1.0%/7.7%/24.3%, respectively, among A2i LDKT recipients vs. 1.8%/8.7%/23.1%, respectively, among comparable recipients in the ABOc LDKT weighted cohort (wHR 0.751.021.40, p=0.9). However, A2i recipients faced higher risk of death-censored graft failure; weighted 1/5/10-year graft failure was 7.9%/16.4%/28.3% for A2i vs. 2.2%/9.7%/20.4% for ABOc recipients (wHR in year 1 = 2.053.766.88; through year 5 = 1.231.983.19; through year 10 = 1.131.672.46). By comparison, 1/5/10-year weighted hazard ratios for death-censored graft failure among A1-incompatible recipients were 0.164.7019.07/0.471.595.35/0.421.213.53. Conclusions: This registry analysis considered the differential risk of A2i LDKT in the United States and demonstrated comparable mortality to ABOc LDKT recipients, but an increased risk of death-censored graft failure for A2i LDKT recipients, particularly in the first year post-transplant. Nonetheless, A2i LDKT remains an excellent treatment option, providing access to LDKT for patients who must otherwise remain on the waitlist in hopes of receiving DDKT. Our findings further the field’s understanding of the risks and benefits of A2i LDKT, and should inform patient counseling, KPD matching algorithms, and post-operative monitoring procedures in the future.K24AI144954 from the National Institute of Allergy and Infectious Diseases (NIAID). K01DK101677 from the National Institute of Diabetes andDigestive and Kidney Diseases (NIDDK).

416.3: Are HLA-A,B,DR and DQ-Mismatching Important for the Kidney Allocation Schemes?-UK Registry Data- an Artificial Intelligence Approach

Introduction: Currently, there is inconsistency among different kidney allocation systems for deceased donors and paired exchange schemes in terms of assessment for HLA-A,B,DR and DQ mismatch. The aim of our study is to assess the effect of HLA-A,B,DR and DQ mismatch on kidney transplant graft survival in the current era. Methodology: All renal transplant patients registered in the United Kingdom Transplant Registry database between January 2005 till January 2015 were retrospectively reviewed. Patients with complete data about HLA-A,D,DR and DQ mismatch were included. Follow up was till April 2021.Patient with complete dataset were included in the study. Recipients with multiple organ transplant, previous renal transplants, or those with missing data about HLA mismatch were excluded from the study. For survival analysis, we fit a penalised Cox model to the entire set of data. We obtained the estimated set of alphas using estimated cross-validated grid-search. The variables included in the penalised cox model donor, recipient and transplant factors in addition to the HLA mismatches. Then we determined the set of alpha for evaluation using optimized cross-validated grid-search. Moreover, we visualised how the coefficients changed for varying α using ridge regression model. The regression models were adjusted for recipient factors (age, sex, ethnicity, diabetes, body mass index), transplant factors (HLA mismatches, calculated reaction frequency, cold ischemia time, delayed graft function, induction, and maintenance immunotherapy) and donor factors (donor type, donor creatinine at time of retrieval, donor age). Results: Median follow-up was 7.5 years. Among living donor kidney transplant recipients (n=4782), Incremental increase in HLA-DR mismatch touched statistical significance and was associated with worse survival (Two HLA-DR: HR=1.31, P=0.05, 95%CI: 1.0-1.72; One HLA-DR mismatch: HR=1.21, P=0.05, 95%CI: 1.00-1.47). None of the other categories of HLA mismatches were associated with worse graft outcomes (P>0.05 for each category).Other factors that played an important role in determining graft survival were delayed graft function (P<0.01), black ethnicity (HR=1.88, 95%CI:1.45-2.51, p<0.01), and donor age (HR=1.02, P<0.01). Among deceased donor kidney transplant recipients (n=7996), None of the HLA mismatches were associated with worse graft survival (P>0.05 for each category of HLA mismatches). The factors that played an important role in determining graft survival were delayed graft function (HR=1.84, 95%CI: 1.67-2.03, P<0.01), black ethnicity (HR=1.42, 95%CI:1.21-1.65, p<0.01), donor age (HR=1.02, P<0.01), and recipient age (HR=0.99, P<0.01). Conclusion: In the current era, HLA-DR mismatches are associated with worse graft outcomes among living donor transplants. However, none of the HLA mismatches are associated with worse graft outcomes among deceased donor kidney transplant recipients. Other factors that play an important role in determining graft survival are delayed graft function, donor age and black ethnicity.

401.1: Impact of HLA-A,B DR and DQ on Living Kidney Transplant Outcomes in the Tacrolimus/MMF Era: An Artificial Intelligence Approach

Introduction: One of the biological barriers that can impact outcomes among Living donor kidney transplantation is HLA mismatch. The aim of our study is to assess the effect of HLA mismatches on acute rejection rates and graft survival in the Tacrolimus era. Moreover, to assess factors affecting survival. Methodology: All Living donor kidney transplant patients registered in UNOS database between 01/01/2005 and 01/12/2019 were retrospectively reviewed. Inclusion criteria: Living donor transplant recipients that were discharged on Tacrolimus/Mycophenolate Mofetil. Exclusion criteria: multiple organ transplants, previous kidney transplants, recipient age<18 years old, deceased donor transplants, missing data about induction therapy, missing HLA mismatch or ABO incompatible transplant. We used double-selection lasso (least absolute shrinkage and selection operator) logistic regression model to assess for acute rejection rates at one-year post-transplant. Variables of interest were HLA-A,B,DR and DQ mismatch. Variables Lasso selected from were: recipient characteristics (age, sex, BMI, ethnicity, diabetes, recipient/donor CMV status, pre-transplant dialysis), donor characteristics (age,ethnicity, diabetes and hypertension) and transplant characteristics (induction therapy, steroid intake, cold ischemia time, delayed graft function, PRA). Acute rejection was defined as biopsy proven or clinically suspected rejection. For survival analysis, we fit a penalised Cox model after choosing best alpha. Cross-validated grid-search was used to evaluate the best alpha. The variables included in the penalised cox model donor, recipient and transplant factors plus HLA mismatches. Results: 28,736 patients were included in our study. Worse acute rejection rates at one-year post-transplant were noted with incremental increase in HLA-DQ (Two HLA-DQ: OR=1.29, P<0.01, 95%CI:1.08-1.54; One HLA DQ:OR=1.22,P=0.01, 95%CI:1.05-1.44), HLA-DR mismatches (Two HLA-DR: OR=1.85, P<0.01, 95%CI:1.48-2.31; One HLA-DR: OR=1.51,p<0.01, 95%CI:1.23-1.85),HLA-B mismatches(Two HLA-B OR=1.33, P=0.01,95%CI:1.05-1.69; One HLA-B mismatch: OR=1.21,P=0.09) and HLA-A mismatch (OR:1.19, P<0.01). In the penalized cox regression model, None of the HLA types (A,B,DR or DQ) were associated with worse graft survival (P>0.05 for every type). The factors that were associated with worse outcomes are: Recipient black ethnicity (HR 1.2, P<0.01, 95%CI:1.10-1.31); delayed graft function (HR=1.54, p<0.01, 95%CI:1.31-1.81), pre-transplant dialysis (HR=1.19,P<0.01, 95%CI:1.12-1.26) and donor Black ethnicity(HR=1.21, P<0.01, 95%CI:1.10-1.33). Conclusion: HLA-DQ, DR,B and A mismatches play a vital role in the occurrence of acute rejection among Living donor kidney transplant recipients. However, HLA mismatches have no significant effect on graft survival. Delayed graft function, pre-transplant dialysis recipient and donor black ethnicity, play an important role in determining graft survival.

P8.052: Long-term Outcomes and Predictors of Graft Function in Living-Donor Preemptive Kidney Transplants

Background: Beyond the new strategies for dialysis treatment, kidney transplantation has already been associated with better outcomes for patients with advanced kidney chronic disease (CKD), and a preemptive kidney transplant seems to be the preferred option for those patients. Thus, this study purposed to evaluate predictors of long-term graft function and unfavorable outcomes in living-donor preemptive kidney transplant recipients. Methods: Single-center cohort study enrolled 222 living-donor preemptive kidney transplant recipients transplanted between 2011 and 2016 and followed up to 2021. Five-year graft function was estimated by CKD-Epi (5-year-eGFR). The primary outcome was composed of death, graft loss, acute rejection, and 5-year-eGFR < 30 mL/min/1.73m2. The multivariable analysis for 5-year-eGFR was performed by linear regression and logistic regression for the primary outcome. Results: Recipients were 40 (31; 48) years old, 59.9% were male, and 35.1% had CKD due to chronic glomerulonephritis. Donors were 48.5 (41.0; 55.2) years old, being most frequently siblings (50%) or parents (28/8%). One-third of patients received ATG as an induction strategy (30.2%), followed by Tacrolimus + azathioprine (59.5%) or cyclosporin + azathioprine (14.4%) or tacrolimus + mycophenolate (11.3%) as the maintenance immunosuppression. The overall incidence of acute rejection, graft loss, and death was 20.3%, 6.3%, and 0.5%, respectively. The median follow-up time was 88.9 months, and the median 5-year-eGFR was 54.7 mL/min. Sixty-five patients presented the primary outcome (29.2%), significantly associated with the HLA compatibility, not using induction therapy and CMV-related event. Compared with identical HLA matches, the OR was 6.81 for haploidentical (P=0.001) and 11.2 for distinct (P<0.001) HLA matches. In addition, the probability for the primary outcome was reduced by 81% (OR= 0.19, p<0.001) for patients who received ATG as induction therapy and 4-fold higher in those who had CMV-related events (OR=4.09; p=0.001). In the linear regression, the association with 5-yr-eGFR was less evident with HLA matches and AR than donor age. Thus, the identical HLA (B= +6.04; p=0.09) match and AR (B=-6.34; p=0.07) tend to be associated with 5-year-eGFR in the linear regression, while donor age (B= -0,69 per year old; p<0.001) presented a significant and inverse association. Conclusion: In recipients of living-donor preemptive kidney transplants, the HLA matches, thymoglobulin induction therapy, and CMV-related events were predictors of composite outcomes of long-term death, graft loss, acute rejection, and low grade of graft function. In addition, only donor age was independently associated with long-term graft function.