Adult Kidney Transplant Recipients Research Articles

Long-term Outcomes of Single and Dual En Bloc Kidney Transplants From Small Pediatric Donors: An ANZDATA Registry Study.

Data were obtained from the Australia and New Zealand Dialysis and Transplant Registry. All adult recipients of kidney transplants from donors aged ≤5 y were identified. The primary outcome of interest was death-censored graft survival by donor type. The secondary outcomes were early graft loss, delayed graft function, serum creatinine posttransplantation, acute rejection, and patient survival. There were 183 adult recipients of kidney transplants from donors aged ≤5 y old. Of these, 60 patients had EBKT grafts, 79 patients had SKT grafts, and 44 patients had grafts of unknown type. Compared with SKT donors, EBKT donors had lower mean age (P < 0.001) and body weight (P < 0.001). There was no significant difference in death-censored graft survival between the groups, with median survival of 23.8 y (interquartile range 21.2-25) in the EBKT cohort and 21.8 y (11.6-26.8) in the SKT cohort (hazard ratio 1.3; 95% confidence interval, 0.59-2.64; P = 0.56). EBKT grafts had lower acute rejection rates than SKT grafts (P = 0.014). There was no significant difference observed between groups with respect to early graft loss, delayed graft function, posttransplantation serum creatinine posttransplantation, or patient survival. EBKT and SKTs from small pediatric donors are associated with excellent long-term graft survival rates.

Tixagevimab-cilgavimab as an Early Treatment for COVID-19 in Kidney Transplant Recipients.

Tixagevimab-cilgavimab as an Early Treatment for COVID-19 in Kidney Transplant Recipients.

Recipient and kidney graft outcomes of deceased donors with human immunodeficiency virus in the United States.

The HIV Organ Policy Equity (HOPE) act afforded transplantation of organs from donors who have HIV. Herein we compared the long-term outcomes of recipients with HIV by donor HIV testing status. Using the Scientific Registry of Transplant Recipients, we identified all primary adult kidney transplant recipients who were HIV-positive between 1/1/16-12/31/21. Recipients were grouped into three cohorts according to the donor HIV status based on antibody (Ab) and nucleic acid testing (NAT): Donor Ab-/NAT- (n=810), Donor Ab+ /NAT- (n=98), and Donor Ab+/NAT+ (n=90). We compared recipient and death-censored graft survival (DCGS) by donor HIV testing status using Kaplan-Meier curves and Cox proportional hazards regression, censored at 3 years posttransplant. Secondary outcomes were delayed graft function (DGF) and the following 1-year outcomes: acute rejection, re-hospitalization, and serum creatinine. In Kaplan-Meier analyses, patient survival and DCGS were similar by donor HIV status (log rank p=.667; log rank p=.388). DGF occurred more frequently in donors with HIV Ab-/NAT- testing compared with Ab+/NAT- or Ab+/NAT+ testing (38.0%vs. 28.6%vs. 26.7%, p=.028). Average dialysis time before transplant was twice as long for recipients who received organs from donors with Ab-/NAT- testing (p<.001). Acute rejection, re-hospitalization and serum creatinine at 12 months did not differ between the groups. Patient and allograft survival for recipients living with HIV remains comparable irrespective of donor HIV testing status. Utilizing kidneys from deceased donors with HIV Ab+/NAT- or Ab+/NAT+ testing shortens dialysis time prior to transplant.

Metabolic acidosis in pediatric kidney transplant recipients.

Metabolic acidosis is a risk factor for faster kidney function decline in chronic kidney disease (CKD) and in adult kidney transplant recipients (KTRs). We hypothesized that metabolic acidosis would be highly prevalent and associated with worse allograft function in pediatric KTRs. Pediatric KTRs at Montefiore Medical Center from 2010 to 2018 were included. Metabolic acidosis was defined as serum bicarbonate < 22mEq/L or receiving alkali therapy. Regression models were adjusted for demographic factors and donor/recipient characteristics. Sixty-three patients were identified with a median age at transplant of 10.5 (interquartile range (IQR) 4.4-15.2) years and post-transplant follow-up of 3 (IQR 1-5) years. Baseline serum bicarbonate was 21.7 ± 2.4mEq/L, serum bicarbonate < 22mEq/L was present in 28 (44%), and 44% of all patients were receiving alkali therapy. The prevalence of acidosis ranged from 58 to 70% during the first year of follow-up. At baseline, each 1-year higher age at transplant and every 10ml/min/1.73m2 higher eGFR were associated with 0.16mEq/L (95% CI: 0.03-0.3) and 0.24mEq/L (95% CI: 0.01-0.5) higher serum bicarbonate, respectively. Older age at transplant was associated with lower odds of acidosis (OR: 0.84; 95% CI: 0.72-0.97). During follow-up, metabolic acidosis was independently associated with 8.2ml/min/1.73m2 (95% CI 4.4-12) lower eGFR compared to not having acidosis; furthermore, eGFR was significantly lower among KTRs with unresolved acidosis compared with resolved acidosis. Among pediatric KTRs, metabolic acidosis was highly prevalent in the first year post-transplantation and was associated with lower eGFR during follow-up. A higher resolution version of the Graphical abstract is available as Supplementary information.

Vegetable Intake, but Not Fruit Intake Is Inversely Associated With Fasting Plasma Glucose in Kidney Transplant Recipients

The association between dietary intake and glycemic control has been extensively investigated in type 2 diabetes. However, little is known about this association in kidney transplant recipients (KTRs). We performed an observational study involving 263 adult KTRs with a functioning allograft for at least 1 year at the outpatient clinic of the Hospital from November 2020 to March 2021. Dietary intake was assessed by food frequency questionnaire. Linear regression analyses were performed to evaluate the association between fruit and vegetable intake and fasting plasma glucose. The vegetable and fruit intake were 238.24 g/d (102.38-416.67) and 511.94 g/d (321.19-849.05), respectively. The fasting plasma glucose was 5.15 ± 0.95 mmol/L. The linear regressions revealed that vegetable intake, but not fruit intake was inversely associated with fasting plasma glucose in KTRs (adjusted R2=0.203, P < .001). The clear dose-response relation was observed. Moreover, each 100 g increase in vegetable intake was associated with 11.6% reduction of fasting plasma glucose. Vegetable intake, but not fruit intake, is inversely associated with fasting plasma glucose in KTRs.

Role of standard HLA mismatch in modifying associations between non-pharmacologic risk factors and solid organ malignancy after kidney transplantation

BackgroundHuman leukocyte antigen mismatch(es) (HLA-mm) between donors and recipients has not been extensively studied either as a risk factor for solid organ malignancy (SOM) or as a modifier of associations between nonpharmacologic risk factors and SOM in kidney transplant recipients (KTRs). MethodsIn a secondary analysis from a previous study, 166,256 adult KTRs in 2000–2018 who survived the first 12 months post-transplant free of graft loss or malignancy were classified into 0, 1–3, and 4–6 standard HLA-mm cohorts. Multivariable cause-specific Cox regressions analyzed the risks of SOM and all-cause mortality (ac-mortality) in 5 years following the first KT year. Comparisons of associations between SOM and risk factors in HLA mismatch cohorts were made by estimating the ratios of adjusted hazard ratios. ResultsCompared with 0 HLA-mm, 1–3 HLA-mm was not associated, and 4–6 HLA-mm was equivocally associated with increased risk of SOM [hazard ratio, (HR) = 1.05, 95%, confidence interval (CI) = 0.94–1.17 and HR = 1.11, 95% CI = 1.00–1.34, respectively]. Both 1–3 HLA-mm and 4–6 HLA-mm were associated with increased risk of ac-mortality compared with 0 HLA mm [hazard ratio (HR) = 1.12, 95%, Confidence Interval (CI) = 1.08–1.18) and (HR = 1.16, 95% CI = 1.09–1.22), respectively]. KTR's history of pre-transplant cancer, age 50–64, and >/=65 years were associated with increased risks of SOM and ac-mortality in all HLA mismatch cohorts. Pre-transplant dialysis >2 years, diabetes as the primary renal disease, and expanded or standard criteria deceased donor transplantation were risk factors for SOM in the 0 and 1–3 HLA-mm cohorts and of ac-mortality in all HLA-mm cohorts. KTRs male sex or history of previous kidney transplant was a risk factor for SOM in the 1–3 and 4–6 HLA-mm cohorts and of ac-mortality in all HLA-mm cohorts. ConclusionDirect association between SOM and the degree of HLA mismatching is equivocal and limited to the 4–6 HLA-mm stratum; however, the degree of HLA mismatching has significant modifying effects on the associations between specific nonpharmacologic risk factors and SOM in KTRs.

#3440 TOCILIZUMAB INDUCTION THERAPY IN KIDNEY TRANSPLANTATION

Abstract Background and Aims Antibody induction therapy is frequently used as an adjunct to the maintenance immunosuppression in adult kidney transplant recipients (KTRs). There are few comparisons of antibody induction therapy allowing early glucocorticoid withdrawal in KTRs. The purpose of the present study was to compare induction therapy involving tocilizumab with the most commonly used induction regimens in patient populations at either high immunologic risk or low immunologic risk. Method In this prospective study, we randomly assigned patients to receive tocilizumab or conventional induction therapy such as basiliximab. Patients were stratified according to acute rejection risk, with a high risk defined by a repeat transplant, a peak or current value of panel-reactive antibodies of 30% or more. The 102 high-risk patients received tocilizumab (one dose of 8 mg/kg, in 52 patients) or basiliximab (a total of 40 mg over 4 days, in 50 patients). The 113 low-risk patients received tocilizumab (one dose of 8 mg/kg, in 62 patients) or basiliximab (a total of 40 mg over 4 days, in 51 patients). All patients received tacrolimus and mycophenolate mofetil and underwent a 10-days glucocorticoid (prednisone) taper in a regimen of early steroid withdrawal. The primary end point was biopsy-confirmed acute rejection at 6 months and 12 months. Patients were followed for 2 years for safety and efficacy end points. Results The rate of biopsy-confirmed acute rejection was significantly lower in the tocilizumab group than in the basiliximab group at both 6 months (5.3% vs. 10.9%, P&amp;lt;0.01) and 12 months (7.9% vs. 12.9%, P&amp;lt;0.01). At 2 years, the rate of biopsy-confirmed acute rejection in low-risk patients was lower with tocilizumab than with basiliximab (9.7% vs. 17.7%, P&amp;lt;0.05), but among high-risk patients, no significant difference was seen between tocilizumab and basiliximab (19.2% vs. 16.0%, P = 0.68). Adverse-event rates were similar among all four treatment groups. Conclusion By the first year after transplantation, biopsy-confirmed acute rejection was less frequent with tocilizumab than with conventional therapy. The apparent superiority of tocilizumab with respect to early biopsy-confirmed acute rejection was restricted to patients at low risk for transplant rejection; among high-risk patients, tocilizumab and basiliximab had similar efficacy. Further randomized and controlled studies are needed to support these results.

#6833 ARE KT RECIPIENTS TAKING THEIR IMMUNOSUPPRESSANT MEDICATION? PRELIMINARY EVIDENCE FROM A SUPER-SPECIALIZED TRANSPLANT CENTRE IN SUB-SAHARAN AFRICA

Abstract Background and Aims Immunosuppressant non-adherence is a leading cause of preventable renal allograft dysfunction, rejection and graft loss. The barriers to immunosuppressant adherence as well as associated risk factors of non-adherence vary across studies in different locations. This study aimed to investigate the prevalence of immunosuppressant non-adherence among adult kidney transplant recipients and identify barriers to adherence in a renal transplant cohort. Method A cross sectional survey was conducted using the Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS), the Immunosuppressant Therapy Barrier Scale and the Beliefs about Medicines Questionnaire. Adherence was defined according to the BAASIS, with barriers to adherence and beliefs about medicines compared between the two groups. Participants were recruited from the out-patient clinic at Zenith Medical and Kidney centre. An advert for the study was placed in consultation rooms and patients were approached to join the study when they attend appointments. IBM SPSS Statistics for Windows, Version 23 (Armonk, NY: IBM Corp) was used for data analysis. Results The rate of non-adherence was 50.7% out of 67 kidney transplant recipients attending outpatient clinic. There were statistically significant associations between non-adherence and occupation (P = 0.049). Participants who are on MMF were more adherent than those on sirolimus (97.0% vs 79.4% and 0.0% vs 8.8%) and this difference is statistically significant (P = .038). Also, participants who have had one or more post-transplant hospital admission are more non-adherent when compared with those that have never been admitted (P = .022) The only significant barrier to adherence was when patients travelled out of town (P &amp;lt; 0.005). Adherence was not associated with patients’ belief about their medicines. Conclusion Interventions aimed at ensuring constant access to immunosuppressant drugs and those based on habit forming may significantly improve adherence in this cohort.

#4953 IMPACT OF IMMUNOSUPPRESSIVE REGIMEN ON ANTIBODY RESPONSE AFTER CHADOX1 NCOV-19 VACCINATION IN THAI KIDNEY TRANSPLANT RECIPIENTS

Abstract Background and Aims The lower humoral immunity response after COVID-19 vaccine in kidney transplant recipients (KTRs) has been reported in several studies. However, the study regarding efficacy of ChAdOx1 nCoV-19 (AstraZeneca) vaccine among various immunosuppressive treatments in Asian population is scarce. Method We conducted a cross-sectional study in Siriraj Hospital, Bangkok, Thailand. Adult KTRs who received two doses of the ChAdOx1 nCoV-19 vaccine at intervals of 3 months were enrolled. Anti-SARS-COV-2 S-RBD-IgG antibody (anti-RBD) was assessed at the one month after the second vaccine dose and considered positive if the level ≥ 50 AU/ml. Primary outcome was seropositivity of anti-RBD. Association between type, dose and level of immunosuppressive regimen, and seropositivity of anti-RBD were analyzed. The statistical analysis was performed using SPSS version 23.0. Results Between October 2021 and January 2022, 153 KTRs with median follow up time of 59 (30 – 125) months, were enrolled. Mean age was 49.3 ± 11 years and 61.4% were male. Regimen of tacrolimus (TAC)/mycophenolate (MPA)/prednisolone (CS), everolimus (EVR)/MPA/CS and TAC/EVR/CS were prescribed for 92 (60.1%), 23 (15%) and 24 (15.7%) patients, respectively. The anti-RBD ≥ 50 AU/ml after vaccination was observed in 82 patients (53.6%) with median level of 476.7 (129 – 1253.2) AU/ml. Patients received TAC/EVR/CS had significantly higher proportion of seropositivity than EVR/MPA/CS (95.8% vs 65.2%; p = 0.008) and TAC/MPA/CS regimen (95.8% vs 37%; p &amp;lt; 0.001). Among the seropositive KTRs, the median level of anti-S is significantly highest in TAC/EVR/CS treatment when compared to EVR/MPA/CS and TAC/MPA/CS group, respectively (1,204 vs 260.7 vs 315.4; p &amp;lt; 0.001). Among KTRs who received tacrolimus, the seropositivity was significantly higher in patients who had tacrolimus trough level &amp;lt; 3 ng/mL (83.3% vs 45.7%; p = 0.014). Conclusion The seropositivity of anti-S after vaccination with ChAdOx1 nCoV-19 in KTRs was 53.6% which was lower than general population. KTRs who received TAC/EVR/CS regimen had highest immune response after vaccination, which is relatively comparable to healthy control in Thailand. Immunosuppressive regimen should be considered for vaccine dose and schedule in the future.

#5146 KINETIC ESTIMATION OF GFR AND URINARY CREATININE EXCRETION RATE AS PREDICTORS OF DELAYED GRAFT FUNCTION IN RENAL TRANSPLANTS FROM DECEASED DONORS

Abstract Background and Aims Delayed graft function (DGF) is a common complication after renal transplant. Definitions of DGF are based on analysis of estimated glomerular filtration rate (eGFR) underlying the plasma creatinine fluctuations after renal transplant. We tried to validate an early parameter of DGF in a renal transplant population based on the kinetic estimation of glomerular filtration rate, since this formula adds a quantitative dimension to the assessment of kidney function, and consequently predicting DGF could get a better post-transplant management. Method This is a longitudinal study of 886 renal transplant recipients from our center during the first post-transplant month. As we are searching for functional biochemical markers in renal transplant from decesased donors, we excluded patients with primary gtaft disfunction.The final simple was composed of 574 adult kidney transplant recipients, 348 renal transplant from donors after circulatory death (DCD) and 226 from donors after brain death (DBD). The following are analyzed 5creatinine concentrations, serum Lactate dehydrogenase (LDH) and urinary creatinine excretion rate (CER). Results In DCD there was a significant correlation between DGF duration and all KeGFR and CER determinations during the first post-transplant week. The parameters that achieved the best correlation to predict DGF were KeGFR (r = 0.515; p&amp;lt;0.001) and CER on the fourth day (r = 0.584; p&amp;lt;0.001) (Figure 1). In the DBD, a weak correlation was observed between DGF duration and KeGFR determinations in the first days, being KeGFR at the fourth day the one that presented the highest correlation (r = 0.59 p&amp;lt;0.001). We observed that serum LDH on the first day in the DBD group is associated with worse renal graft function at first, third month and one year after transplantation (p&amp;lt;.045, p&amp;lt;.05 and p&amp;lt;.067 respectively). Conclusion The determination of KeGFR and CER could predict the duration of DGF, especially in DCD recipients. DCD recipients with DGF have significantly better graft survival at one year than DBD recipients with DGF. (p&amp;lt;.001).

Letermovir vs Valganciclovir for Prophylaxis of Cytomegalovirus in High-Risk Kidney Transplant Recipients

Valganciclovir for 200 days is standard care for cytomegalovirus (CMV) prophylaxis in high-risk CMV-seronegative kidney transplant recipients who receive an organ from a CMV-seropositive donor, but its use is limited by myelosuppression. To compare the efficacy and safety of letermovir with valganciclovir for prevention of CMV disease in CMV-seronegative kidney transplant recipients who receive an organ from a CMV-seropositive donor. Randomized, double-masked, double-dummy, noninferiority, phase 3 trial in adult CMV-seronegative kidney transplant recipients who received an organ from a CMV-seropositive donor at 94 participating sites between May 2018 and April 2021 (final follow-up in April 2022). Participants were randomized in a 1:1 ratio (stratified by receipt of lymphocyte-depleting induction immunosuppression) to receive letermovir, 480 mg, orally daily (with acyclovir) or valganciclovir, 900 mg, orally daily (adjusted for kidney function) for up to 200 days after transplant, with matching placebos. The primary outcome was CMV disease, confirmed by an independent masked adjudication committee, through posttransplant week 52 (prespecified noninferiority margin, 10%). CMV disease through week 28 and time to onset of CMV disease through week 52 were secondary outcomes. Exploratory outcomes included quantifiable CMV DNAemia and resistance. The rate of leukopenia or neutropenia through week 28 was a prespecified safety outcome. Among 601 participants randomized, 589 received at least 1 dose of the study drug (mean age, 49.6 years; 422 [71.6%] men). Letermovir (n = 289) was noninferior to valganciclovir (n = 297) for prevention of CMV disease through week 52 (10.4% vs 11.8% of participants with committee-confirmed CMV disease; stratum-adjusted difference -1.4% [95% CI, -6.5% to 3.8%]). No participants who received letermovir vs 5 participants (1.7%) who received valganciclovir developed CMV disease through week 28. Time to onset of CMV disease was comparable between the groups (hazard ratio, 0.90 [95% CI, 0.56-1.47]). Quantifiable CMV DNAemia was detected in 2.1% of participants in the letermovir group vs 8.8% in the valganciclovir group by week 28. Of participants evaluated for suspected CMV disease or CMV DNAemia, none (0/52) who received letermovir and 12.1% (8/66) who received valganciclovir had resistance-associated substitutions. The rate of leukopenia or neutropenia through week 28 was lower with letermovir vs valganciclovir (26% vs 64%; difference, -37.9% [95% CI, -45.1% to -30.3%]; P < .001). Fewer participants in the letermovir group than the valganciclovir group discontinued prophylaxis due to adverse events (4.1% vs 13.5%) or drug-related adverse events (2.7% vs 8.8%). Among adult CMV-seronegative kidney transplant recipients who received an organ from a CMV-seropositive donor, letermovir was noninferior to valganciclovir for prophylaxis of CMV disease over 52 weeks, with lower rates of leukopenia or neutropenia, supporting its use for this indication. ClinicalTrials.gov Identifier: NCT03443869; EudraCT: 2017-001055-30.

Pathophysiological Changes in the Hemostatic System and Antithrombotic Management in Kidney Transplant Recipients.

Nowadays, the main cause for early graft loss is renal graft thrombosis because kidney transplant outcomes have improved drastically owing to advances in immunological techniques and immunosuppression. However, data regarding the efficacy of antithrombotic therapy in the prevention of renal graft thrombosis are scarce. Adequate antithrombotic management requires a good understanding of the pathophysiological changes in the hemostatic system in patients with end-stage kidney disease (ESKD). Specifically, ESKD and dialysis disrupt the fine balance between pro- and anticoagulation in the body, and further changes in the hemostatic system occur during kidney transplantation. Consequently, kidney transplant recipients paradoxically are at risk for both thrombosis and bleeding. This overview focuses on the pathophysiological changes in hemostasis in ESKD and kidney transplantation and provides a comprehensive summary of the current evidence for antithrombotic management in (adult) kidney transplant recipients.

A randomized controlled trial of preemptive rituximab to prevent recurrent focal segmental glomerulosclerosis post-kidney transplant (PRI-VENT FSGS): protocol and study design.

Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage kidney disease requiring kidney transplantation and can recur in the allograft in 30-80% of recipients resulting in reduced graft survival. Plasmapheresis has shown efficacy in treating some cases of recurrent FSGS but isolated plasmapheresis has not demonstrated efficacy in preventing recurrent FSGS. Rituximab has had anecdotal success in preventing recurrence in a single center study but has not been studied in combination with plasmapheresis for preventing FSGS recurrence. We are conducting a randomized, controlled, multicenter clinical trial of adult and pediatric kidney transplant recipients with primary FSGS to assess whether plasmapheresis in combination with rituximab prevents recurrent disease post-transplantation. Rituximab combined with plasmapheresis is a promising, novel therapy to prevent recurrent FSGS, a disease with limited therapeutic options and no consensus guidelines for prevention or treatment. https://clinicaltrials.gov/ct2/show/NCT03763643, identifier NCT03763643.

Incidence of Thromboembolic Complications Following Kidney Transplantation with Short and Extended Aspirin Prophylaxis: A Retrospective Single-Center Study.

BACKGROUND Aspirin prophylaxis has been associated with reduced graft-related thrombosis following kidney transplantation. Aspirin cessation, however, can increase risk of venous thromboembolic complications, including pulmonary thromboembolism and deep venous thrombosis. This single-center, retrospective, pre-post interventional study from Brisbane, Australia, aimed to compare the rate of thrombotic complications in 1208 adult kidney transplant recipients receiving postoperative aspirin for 5 days or >6 weeks. MATERIAL AND METHODS We enrolled1208 kidney transplant recipients who received 100 mg aspirin for 5 days (n=571) or >6 weeks (n=637) postoperatively. The primary outcome was venous thromboembolism (VTE) in the first 6 weeks after transplant, examined by multivariable logistic regression analysis. Secondary outcomes were renal vein/artery thrombosis, 1-month serum creatinine, rejection, myocardial infarction, stroke, blood transfusion, dialysis at day 5 and day 28, and mortality. RESULTS Sixteen (1.3%) patients experienced VTE (5-day n=8, 1.4%; >6-week n=8, 1.3%; P=0.8). Extended aspirin duration was not independently associated with a reduction in VTE (OR 0.91, 95% CI 0.32-2.57; P=0.9). Graft thrombosis was rare (n=3, 0.25%). Aspirin duration was not associated with cardiovascular events, blood transfusion, graft thrombosis, graft dysfunction, rejection, or mortality. VTE was independently associated with older age (OR 1.09, 95% CI 1.04-1.16; P=0.002), smoking (OR 3.59, 95% CI 1.20-13.2; P=0.032), younger donor age (OR 0.96, 95% CI 0.93-1.00; P=0.036), and thymoglobulin use (OR 10.5, 95% CI 3.09-32.1; P≥0.001). CONCLUSIONS Extended-duration aspirin use did not significantly reduce the incidence of VTE in the first 6 weeks following kidney transplantation. An association was identified between anti-human thymocyte immunoglobulin and VTE, which requires further assessment.

An automated histological classification system for precision diagnostics of kidney allografts.

For three decades, the international Banff classification has been the gold standard for kidney allograft rejection diagnosis, but this system has become complex over time with the integration of multimodal data and rules, leading to misclassifications that can have deleterious therapeutic consequences for patients. To improve diagnosis, we developed a decision-support system, based on an algorithm covering all classification rules and diagnostic scenarios, that automatically assigns kidney allograft diagnoses. We then tested its ability to reclassify rejection diagnoses for adult and pediatric kidney transplant recipients in three international multicentric cohorts and two large prospective clinical trials, including 4,409 biopsies from 3,054 patients (62.05% male and 37.95% female) followed in 20 transplant referral centers in Europe and North America. In the adult kidney transplant population, the Banff Automation System reclassified 83 out of 279 (29.75%) antibody-mediated rejection cases and 57 out of 105 (54.29%) T cell-mediated rejection cases, whereas 237 out of 3,239 (7.32%) biopsies diagnosed as non-rejection by pathologists were reclassified as rejection. In the pediatric population, the reclassification rates were 8 out of 26 (30.77%) for antibody-mediated rejection and 12 out of 39 (30.77%) for T cell-mediated rejection. Finally, we found that reclassification of the initial diagnoses by the Banff Automation System was associated with an improved risk stratification of long-term allograft outcomes. This study demonstrates the potential of an automated histological classification to improve transplant patient care by correcting diagnostic errors and standardizing allograft rejection diagnoses.ClinicalTrials.gov registration: NCT05306795 .

Postoperative length of stay following kidney transplantation in patients without delayed graft function-An analysis of center-level variation and patient outcomes.

Early discharge after surgical procedures has been proposed as a novel strategy to reduce healthcare expenditures. However, national analyses of the association between discharge timing and post-transplant outcomes following kidney transplantation are lacking. This was a retrospective cohort study of all adult kidney transplant recipients without delayed graft function from 2014 to 2019 in the Organ Procurement and Transplantation Network and Nationwide Readmissions Databases. Recipients were divided into Early (LOS≤4 days), Routine (LOS 5-7), and Delayed (LOS>7) cohorts. Of 61798 kidney transplant recipients, 26821 (43%) were discharged Early and 23279 (38%) Routine. Compared to Routine, patients discharged Early were younger (52 [41-61] vs. 54 [43-62] years, p<.001), less commonly Black (33% vs. 34%, p<.001), and more frequently had private insurance (41% vs. 35%, p<.001). After adjustment, Early discharge was not associated with inferior 1-year patient survival (Hazard Ratio [HR] .74, 95% Confidence Interval [CI] 0.66-0.84) or increased likelihood of nonelective readmission at 90-days (HR .93, CI .89-.97), relative to Routine discharge. Discharging all Routine patients as Early would result in an estimated cost saving of ∼$40 million per year. Multi-level modeling of post-transplantation LOS revealed that 28.8% of the variation in LOS was attributable to interhospital differences rather than patient factors. Early discharge after kidney transplantation appears to be cost-efficient and not associated with inferior post-transplant survival or increased readmission at 90 days. Future work should elucidate the benefits of early discharge and develop standardized enhanced recovery protocols to be implemented across transplant centers.

Recipient race modifies the association between obesity and long-term graft outcomes after kidney transplantation

Donor and recipient obesity (defined using body mass index [BMI]) are associated with worse outcomes after kidney transplant (KT). In adult KT recipients identified using the Scientific Registry of Transplant Recipients (2000-2017), we examined the modifying effect of recipient race on recipient obesity (BMI > 30 kg/m2) and combined donor and recipient (DR) obesity pairing, with death-censored graft loss (DCGL), all-cause graft loss (ACGL), and short-term graft outcomes using multivariable Cox proportional hazards models and logistic regression. Obesity was associated with a higher risk of DCGL in White (adjusted hazard ratio [aHR], 1.29; 95% CI, 1.25-1.35) than Black (aHR, 1.13; 95% CI, 1.08-1.19) recipients. White, but not Black, recipients with obesity were at higher risk for ACGL (aHR, 1.08; 95% CI, 1.05-1.11, for White recipients; aHR, 0.99; 95% CI, 0.95-1.02, for Black recipients). Relative to nonobese DR, White recipients with combined DR obesity experienced more DCGL (aHR, 1.38; 95% CI, 1.29-1.47 for White; aHR, 1.19; 95% CI, 1.10-1.29 for Black) and ACGL (aHR, 1.12; 95% CI, 1.07-1.17 for White; aHR, 1.00; 95% CI, 0.94-1.07 for Black) than Black recipients. Short-term obesity risk was similar irrespective of race. An elevated BMI differentially affects long-term outcomes in Black and White KT recipients; uniform BMI thresholds to define transplant eligibility are likely inappropriate.

Outcome of Brain Lymphoma in a High Epstein-Barr Virus–Prevalence Country After Kidney Transplantation

The incidence of post-transplant lymphoproliferative disorder (PTLD) in adult kidney transplant (KTx) recipients is less common in Taiwan. In our institute, we observed that brain lymphoma was the most notorious type. The study describes the clinical, histologic, and radiological features of primary central nervous lymphoma (PCNSL) and the outcomes and associations with Epstein-Barr virus (EBV) infection in our center. Among 1470 KTx recipients, 5 patients had tissue-proven brain lymphoma (0.34%). The brain pathology disclosed diffuse large B-cell lymphoma in all patients. EBV was detected through in situ hybridization for Epstein-Barr encoding region (EBER) to disclose the EBV inclusion in the nuclei of lymphoma cells. The first treatment step was the reduction of immunosuppressants; 4 patients received whole-brain radiotherapy after complete resection of PCNSL, and 1 received concurrent chemoradiotherapy. Only one patient had poor performance status at the time of diagnosis and had a poor response to treatment with steroids. Four patients survived (mean 36.5 months, range 8.6 to 57.6 months), but one died after rapid neurologic deterioration. Epstein-Barr virus inclusion was found in PCNSL in our patients; however, the role of EBV in PCNSL remains to be clarified. Post-transplant lymphoproliferative disorder is a rare malignancy after KTx with a predilection of brain involvement in Taiwan. We report a successful care experience in a patient with primary CNS lymphoma with better survival.

25(OH)D-but not 1,25(OH)2D-Is an independent risk factor predicting graft loss in stable kidney transplant recipients.

Vitamin D deficiency (VDD) or vitamin D insufficiency is common in kidney transplant recipients (KTRs). The impact of VDD on clinical outcomes in KTRs remain poorly defined and the most suitable marker for assessing vitamin D nutritional status in KTRs is unknown so far. We conducted a prospective study including 600 stable KTRs (367 men, 233 women) and a meta-analysis to pool existing evidence to determine whether 25(OH)D or 1,25(OH)2D predicted graft failure and all-cause mortality in stable KTRs. Compared with a higher 25(OH)D concentration, a low concentration of 25(OH)D was a risk factor for graft failure (HR 0.946, 95% CI 0.912-0.981, p = 0.003), whereas 1,25 (OH)2D was not associated with the study end-point graft loss (HR 0.993, 95% CI 0.977-1.009, p = 0.402). No association was found between either 25(OH)D or 1,25 (OH)2D and all-cause mortality. We furthermore conducted a meta-analysis including 8 studies regarding the association between 25(OH)D or 1,25(OH)2D and graft failure or mortality, including our study. The meta-analysis results were consistent with our study in finding that lower 25(OH)D levels were significantly associated with the risk of graft failure (OR = 1.04, 95% CI: 1.01-1.07), but not associated with mortality (OR = 1.00, 95% CI: 0.98-1.03). Lower 1,25(OH)2D levels were not associated with the risk of graft failure (OR = 1.01, 95% CI: 0.99-1.02) and mortality (OR = 1.01, 95% CI: 0.99-1.02). Baseline 25(OH)D concentrations but not 1,25(OH)2D concentrations were independently and inversely associated with graft loss in adult KTRs.

Normal Saline vs Plasma-Lyte A Use Intra- and Post-Operatively in Adult Kidney Transplant Recipients

Fluid management intra- and post-operatively for kidney transplant recipients (KTR) is essential to maintain adequate perfusion to the kidney. 0.9% normal saline (NS) is commonly used, but it can cause hyperchloremic metabolic acidosis, which may result in hyperkalemia and lead to delayed graft function (DGF). Plasma-Lyte A (PA) is an alternative option that has a lower amount of chloride and a neutral pH, which may offset the risk of hyperkalemia. The aim of this study is to determine the incidence of DGF in KTRs comparing NS vs PA use intra- and initially post-operatively. This single-center, retrospective cohort study in adult KTRs from January 1, 2016 to February 1, 2021 consisted of two cohorts, those receiving NS vs PA. Multi-organ transplant recipients were excluded. The primary outcome was the incidence of DGF. A total of 244 KTRs in the NS group and 263 KTRs in the PA group were included. There was no significant difference in incidence of DGF between the groups, (NS 23.4% vs PA 25.9%, p = 0.537). The logistic regression for only deceased donors were not significantly different (OR 1.369 (0.819-2.288). There was no difference in the incidence of DGF when comparing NS vs PA.