Allograft Outcomes Research Articles

344.2: Delta Changes in Donor-Derived Cell-Free DNA (dd-cfDNA) Complement the Donor Fraction in Kidney Transplant Surveillance

Introduction: Delta changes in dd-cfDNA levels over time may identify patients with evolving alloimmune injury, providing complementary information to thedonor fraction. We explored the dd-cfDNA trajectories preceding biopsy-proven rejection (BPAR) events among kidney transplant recipients enrolled in theKidney allograft Outcomes AlloSure Registry (KOAR, NCT03326076) and undergoing longitudinal surveillance with dd-cfDNA. Methods: In the primary analysis, we compared the change in dd-cfDNA from baseline to the time of BPAR (for-cause or surveillance biopsies). We identifiedpatients with first-time rejection events and at least 3 prior dd-cfDNA results; the index result was obtained ≤30 days before BPAR; we then selected the lowestof two preceding results as the patient-specific baseline and compared this with the index result. We then analyzed patients with rejection (first or subsequent, atleast 90 days apart) and ≥2 dd-cfDNA results, including one within 30 days of the index biopsy. The reference change value (RCV) was calculated using areference population of patients with stable allograft function, at least 3 dd-cfDNA measurements, and no significant clinical events. Results: A total of 28 patients with BPAR met criteria for the primary analysis; among these, median baseline dd-cfDNA was 0.22% (IQR: 0.19 - 0.35) and mediandd-cfDNA at the time of rejection was 1.35% (IQR: 0.75 - 2.75), representing a 491% (IQR: 177 - 1133) increase between these results, obtained 71.5 (IQR: 46 -113) days apart (Table 1A).51 events met criteria for the second analysis where a median increase of 253% (IQR: 72 - 821%) between sequential dd-cfDNAvalues obtained 69 days (IQR: 45 - 108) apart preceded biopsy-proven rejection events (Table 1B). The calculated RCV for the stable reference population withinKOAR was 56.3%. 39 of these 51 events (76%) demonstrated increases greater than this RCV. Conclusions: Longitudinal surveillance with dd-cfDNA allows the integration of delta changes and trajectories over time, allowing earlier identification ofevolving allograft injury. Significant changes from an established baseline and between sequential values ahead of biopsy-proven rejection highlight how longitudinal surveillance may improve diagnostic performance.

Timing of Organ Procurement From Brain-Dead Donors Associates With Short- and Long-Term Outcomes After Liver Transplantation.

Brain death-induced cytokine storm is thought to harm transplantable organs. However, longer procurement times have been associated with non-inferior or better outcomes in kidney, heart, and lung transplants, while optimal procurement time for liver allografts is unknown. Our aim was to analyze the association of time interval from brain death to organ procurement with liver allograft outcomes in two nationwide cohorts. The association of procurement interval with graft survival and short-term complications was analysed in multivariable models. Altogether 643 and 58,017 orthotopic liver transplantations from brain-dead donors were included from Finland between June 2004 and December 2017 and the US between January 2008 and August 2018, respectively. Median time from brain death to organ procurement was 10.5 h in Finland and 34.6 h in the US. Longer interval associated with better graft survival (non-linearly, p = 0.016) and less acute rejections (OR 0.935 95% CI 0.894–0.978) in the US cohort, and better early allograft function (p = 0.005; Beta −0.048 95% CI −0.085 −(−0.011)) in the Finnish cohort, in multivariable models adjusted with Donor Risk Index, recipient age, Model for End-Stage Liver Disease and indication for transplantation. Progressive liver injury after brain death is unlikely. Rushing to recover seems unnecessary; rest and repair might prove beneficial.

Risk assessment of human cytomegalovirus infection in solid organ transplantation: Insight into CD4+ T cell subsets

AbstractHuman cytomegalovirus (HCMV) is a significant risk factor for post‐transplant viral infections in organ transplantation, affecting allograft outcomes. Most current methods attempt to predict HCMV viremia or disease by monitoring virus‐specific T cell immunity. This approach may support physicians in limiting treatment toxicity, overmedication, and cost. T cells play an essential role in acquired immunity for stable and long‐term protection against viruses. As a component of cell‐mediated immunity, heterogeneous CD4+ T cells orchestrate immune responses by involving their different subsets, including T helper 1 (Th1), Th2, Th17, Th22, Th9, T follicular helper (Tfh), and T regulatory (Treg). HCMV affects the frequency and phenotype of CD4+ T cells, changing the composition of their subsets during different infection stages. Hypothetically, defining a panel of HCMV‐specific CD4+ T cell subsets and investigating their profile may help classify at‐risk patients. The early detection could be followed by a personalized treatment. This review discusses the frequency changes of CD4+ T cell subsets post‐transplant and their predictive value during HCMV infection.

Allograft versus autograft for reconstruction after resection of primary bone tumors: a comparative study of long-term clinical outcomes and risk factors for failure of reconstruction

There have been no studies comparing the outcomes of nonvascularized autograft (NA) and allograft after resection of primary bone tumors. This study compares the clinical, functional outcomes of NA and allograft reconstruction and analyzes the risk factors for failure after these procedures. A retrospective study of patients with primary bone tumors of the extremities who underwent NA (n = 50) and allograft reconstruction (n = 47). The minimum follow up time was 24 months. The mean time to union for the NA and allograft group was 9.8 ± 2.9 months and 11.5 ± 2.8 months, respectively (p = 0.002). Reconstruction failure in the NA and allograft group was 19 (38%) and 26 (55.3%), respectively. Nonunion (30%) was the most common complication found in the NA group, while structural failure (29.8%) was the most common in the allograft group. There was no significant difference in functional outcome in terms of the mean Musculoskeletal Tumor Society score between the NA and allograft groups (23.5 ± 2.8 and 23.9 ± 2.1, respectively, p = 0.42). Age, sex, tumor location, graft length, method of reconstruction did not significantly influence failure of reconstruction. Chemotherapy was the only significant risk factor affecting outcomes (HR = 3.49, 95% CI = 1.59–7.63, p = 0.002). In the subgroup analysis, the use of chemotherapy affected graft-host nonunion (p < 0.001) and structural failure in both the NA and allograft groups (p = 0.02). Both NA and allograft reconstruction methods provide acceptable clinical and functional outcomes. Chemotherapy is a risk factor for failure of both reconstructions, particularly graft-host nonunion and structural failure.

Donor-derived Cell-free DNA Measurement in Kidney Transplant Patients Without Allograft Dysfunction: More Evidence and More Questions.

Donor-derived Cell-free DNA Measurement in Kidney Transplant Patients Without Allograft Dysfunction: More Evidence and More Questions.

The Korean Organ Transplantation Registry (KOTRY): an overview and summary of the kidney-transplant cohort.

BackgroundAs the need for a nationwide organ-transplant registry emerged, a prospective registry, the Korean Organ Transplantation Registry (KOTRY), was initiated in 2014. Here, we present baseline characteristics and outcomes of the kidney-transplant cohort for 2014 through 2019.MethodsThe KOTRY consists of five organ-transplant cohorts (kidney, liver, lung, heart, and pancreas). Data and samples were prospectively collected from transplant recipients and donors at baseline and follow-up visits; and epidemiological trends, allograft outcomes, and patient outcomes, such as posttransplant complications, comorbidities, and mortality, were analyzed.ResultsFrom 2014 to 2019, there were a total of 6,129 registered kidney transplants (64.8% with living donors and 35.2% with deceased donors) with a mean recipient age of 49.4 ± 11.5 years, and 59.7% were male. ABO-incompatible transplants totaled 17.4% of all transplants, and 15.0% of transplants were preemptive. The overall 1- and 5-year patient survival rates were 98.4% and 95.8%, respectively, and the 1- and 5-year graft survival rates were 97.1% and 90.5%, respectively. During a mean follow-up of 3.8 years, biopsy-proven acute rejection episodes occurred in 17.0% of cases. The mean age of donors was 47.3 ± 12.9 years, and 52.6% were male. Among living donors, the largest category of donors was spouses, while, among deceased donors, 31.2% were expanded-criteria donors. The mean serum creatinine concentrations of living donors were 0.78 ± 0.62 mg/dL and 1.09 ± 0.24 mg/dL at baseline and 1 year after kidney transplantation, respectively.ConclusionThe KOTRY, a systematic Korean transplant cohort, can serve as a valuable epidemiological database of Korean kidney transplants.

Incidence, Risk Factors, and Effect on Allograft Survival of Glomerulonephritis Post-transplantation in a United Kingdom Population: Cohort Study.

Post-transplant glomerulonephritis (PTGN) has been associated with inferior long-term allograft survival, and its incidence varies widely in the literature. This is a cohort study of 7,623 patients transplanted between 2005 and 2016 at four major transplant UK centres. The diagnosis of glomerulonephritis (GN) in the allograft was extracted from histology reports aided by the use of text-mining software. The incidence of the four most common GN post-transplantation was calculated, and the risk factors for disease and allograft outcomes were analyzed. In total, 214 patients (2.8%) presented with PTGN. IgA nephropathy (IgAN), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), and membranoproliferative/mesangiocapillary GN (MPGN/MCGN) were the four most common forms of post-transplant GN. Living donation, HLA DR match, mixed race, and other ethnic minority groups were associated with an increased risk of developing a PTGN. Patients with PTGN showed a similar allograft survival to those without in the first 8 years of post-transplantation, but the results suggest that they do less well after that timepoint. IgAN was associated with the best allograft survival and FSGS with the worst allograft survival. PTGN has an important impact on long-term allograft survival. Significant challenges can be encountered when attempting to analyze large-scale data involving unstructured or complex data points, and the use of computational analysis can assist.

Predictive Value of HAS-BLED Score Regarding Bleeding Events and Graft Survival following Renal Transplantation.

Objective: Due to the high prevalence and incidence of cardio- and cerebrovascular diseases among dialysis-dependent patients with end-stage renal disease (ERSD) scheduled for kidney transplantation (KT), the use of antiplatelet therapy (APT) and/or anticoagulant drugs in this patient population is common. However, these patients share a high risk of complications, either due to thromboembolic or bleeding events, which makes adequate peri- and post-transplant anticoagulation management challenging. Predictive clinical models, such as the HAS-BLED score developed for predicting major bleeding events in patients under anticoagulation therapy, could be helpful tools for the optimization of antithrombotic management and could reduce peri- and postoperative morbidity and mortality. Methods: Data from 204 patients undergoing kidney transplantation (KT) between 2011 and 2018 at the University Hospital Leipzig were retrospectively analyzed. Patients were stratified and categorized postoperatively into the prophylaxis group (group A)—patients without pretransplant anticoagulation/antiplatelet therapy and receiving postoperative heparin in prophylactic doses—and into the (sub)therapeutic group (group B)—patients with postoperative continued use of pretransplant antithrombotic medication used (sub)therapeutically. The primary outcome was the incidence of postoperative bleeding events, which was evaluated for a possible association with the use of antithrombotic therapy. Secondary analyses were conducted for the associations of other potential risk factors, specifically the HAS-BLED score, with allograft outcome. Univariate and multivariate logistic regression as well as a Cox proportional hazard model were used to identify risk factors for long-term allograft function, outcome and survival. The calibration and prognostic accuracy of the risk models were evaluated using the Hosmer–Lemshow test (HLT) and the area under the receiver operating characteristic curve (AUC) model. Results: In total, 94 of 204 (47%) patients received (sub)therapeutic antithrombotic therapy after transplantation and 108 (53%) patients received prophylactic antithrombotic therapy. A total of 61 (29%) patients showed signs of postoperative bleeding. The incidence (p < 0.01) and timepoint of bleeding (p < 0.01) varied significantly between the different antithrombotic treatment groups. After applying multivariate analyses, pre-existing cardiovascular disease (CVD) (OR 2.89 (95% CI: 1.02–8.21); p = 0.04), procedure-specific complications (blood loss (OR 1.03 (95% CI: 1.0–1.05); p = 0.014), Clavien–Dindo classification > grade II (OR 1.03 (95% CI: 1.0–1.05); p = 0.018)), HAS-BLED score (OR 1.49 (95% CI: 1.08–2.07); p = 0.018), vit K antagonists (VKA) (OR 5.89 (95% CI: 1.10–31.28); p = 0.037), the combination of APT and therapeutic heparin (OR 5.44 (95% CI: 1.33–22.31); p = 0.018) as well as postoperative therapeutic heparin (OR 3.37 (95% CI: 1.37–8.26); p < 0.01) were independently associated with an increased risk for bleeding. The intraoperative use of heparin, prior antiplatelet therapy and APT in combination with prophylactic heparin was not associated with increased bleeding risk. Higher recipient body mass index (BMI) (OR 0.32 per 10 kg/m2 increase in BMI (95% CI: 0.12–0.91); p = 0.023) as well as living donor KT (OR 0.43 (95% CI: 0.18–0.94); p = 0.036) were associated with a decreased risk for bleeding. Regarding bleeding events and graft failure, the HAS-BLED risk model demonstrated good calibration (bleeding and graft failure: HLT: chi-square: 4.572, p = 0.802, versus chi-square: 6.52, p = 0.18, respectively) and moderate predictive performance (bleeding AUC: 0.72 (0.63–0.79); graft failure: AUC: 0.7 (0.6–0.78)). Conclusions: In our current study, we could demonstrate the HAS-BLED risk score as a helpful tool with acceptable predictive accuracy regarding bleeding events and graft failure following KT. The intensified monitoring and precise stratification/assessment of bleeding risk factors may be helpful in identifying patients at higher risks of bleeding, improved individualized anticoagulation decisions and choices of antithrombotic therapy in order to optimize outcome after kidney transplantation.

Short-term kidney transplant outcomes from severe acute respiratory syndrome coronavirus 2 lower respiratory tract positive donors.

ObjectiveIn this study, we aim to assess short‐term allograft outcomes following deceased donor kidney transplantation from severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) lower respiratory tract (LRT) nucleic acid testing (NAT) positive donors.MethodsFrom September to December 2021, SARS‐CoV‐2 NAT positive organ donors, whose solid abdominal organs were transplanted at our academic medical center were identified. Donors were stratified into having tested positive for SARS‐CoV‐2 in an upper respiratory tract (URT) or LRT sample. For this study, the SARS‐CoV‐2 LRT NAT positive deceased kidney donors and their respective recipients were examined. Donor and recipient demographic data, coronavirus disease 2019 (COVID‐19)‐related history, patient outcomes, as well as postoperative graft function were evaluated.ResultsThirteen SARS‐CoV‐2 positive deceased donors were identified. Of these, eight were LRT NAT positive and yielded nine kidneys. These allografts were successfully transplanted into vaccinated and unvaccinated recipients. All recipients received standard induction immunosuppression and did not receive any prophylactic therapy for SARS‐CoV‐2. Two recipients had delayed graft function. At 1‐month post‐transplant, there was no clinical evidence of donor‐derived COVID‐19 or graft loss, and all recipients were free from dialysis.ConclusionWe describe the first case series of SARS‐CoV‐2 LRT NAT positive deceased kidney donors for vaccinated and unvaccinated recipients with excellent short‐term allograft outcomes and no clinical evidence of donor‐derived COVID‐19 post‐transplantation. Given the increasing prevalence of SARS‐CoV‐2 in the population, utilization of SARS‐CoV‐2 LRT NAT positive deceased donors could be considered an acceptable source of organs for renal transplantation, especially as multi‐center experiences and longer‐term follow‐up emerge.

Clinical indicators of slow graft function and outcome after pediatric kidney transplantation.

Lesser degrees of perioperative ischemia-reperfusion injury that does not require dialysis may nonetheless influence allograft outcomes, necessitating evaluation of suitable surrogate indicators of perioperative allograft injury. This retrospective analysis of pediatric kidney transplants evaluated two indicators representing pace and completeness of recovery, for association with 12-month estimated glomerular filtration rate (eGFR) and first-year rate of eGFR decline: time to creatinine nadir (TTN) and ratio of recipient/donor unadjusted GFR (uGFRR/D ) at 1-month post-transplant. Donor, recipient, and perioperative risk factors were tested further for association with these 2 indicators. 179 patients (190 transplants) aged 13 (IQR 7-17) years and 56% male were included. Twelve-month eGFR was strongly associated with unadjusted GFR at 1 month (uGFR1M , p < .001) and uGFRR/D (p=.003), but not with TTN. None of the indicators was associated with the rate of subsequent eGFR decline after 1-month post-transplant. As a potential surrogate indicator, uGFR1M is effectively modeled by TTN and uGFRR/D (adjusted R2 =0.57) and is associated with 12-month eGFR (β=0.81 ± 0.08; p < .001). Clinical factors associated with uGFRR/D included donor uGFR (p < .001), BSA (p=.026), age (p=.074), and recipient BSA (p < .001). Factors associated with pace of recovery (TTN) included donor uGFR (p=.018), type (p=.019), and recipient BSA (p=.022). The uGFRR/D ratio, but not TTN, is a useful indicator of perioperative allograft damage that is associated with one-year functional outcome; and uGFR1M is a potential early surrogate outcome. Donor, recipient, and perioperative factors that are associated with slow allograft function are identified.

Management of postkidney transplant anemia – is it feasible to maintain patient and allograft survival?

Background Kidney transplantation has been established as the best therapy for end-stage renal disease. After transplantation and to provide a prolonged and safe patient and allograft survival, early and prompt diagnosis of posttransplant sequelae, for example, posttransplant anemia (PTA) in particular, is currently crucial. Timing of presentation of this disease has its effect on PTA development. The ‘early’ presented PTA (before 6 months) may differ clinically from the ‘late’ one (after 6 months) with respect to the underlying background. Although early PTA is multifactorial, allograft dysfunction is usually the underlying mechanism in the ‘late’ one. Furthermore, PTA is currently considered as an independent risk factor for the evolution of cardiovascular system events; the latter has been proved to be the first leading cause of death in this cohort of patients. The aims and objectives of this review is to evaluate critically the risk factors responsible for PTA development, its epidemiology, diagnostic criteria, etiology for both ‘early’ and ‘late’ PTA, the available therapeutic approaches for PTA, as well as the effect of PTA in allograft and patient survival. Methods Current available literature and analysis of various trials concerned with PTA. Results The impact of anemia on patients as well as allograft outcomes cannot be simply overlooked. Management of the early as well as late PTA is crucial. However, a variety of hazards of its therapeutic options should be thoroughly considered. Conclusions A lowered threshold of post-transplant anemia (PTA) awareness and its early management has its crucial impact on allograft as well as patient survival. Benefits of PTA correction is not only reflected on patients’ and allograft longevity but also on upgrading KTRs’ quality of life.

Risk Factors of Early Allograft Dysfunction in Patients With Hepatitis B Virus-Related Acute-on-Chronic Liver Failure After Deceased Donor Liver Transplant

Hepatitis B virus-related acute-on-chronic liver failure remains a life-threatening syndrome, and transplant is the definitive treatment. Early allograft dysfunction is a postoperative complication and affects morbidity and mortality. We studied the risk factors associated with early allograft dysfunction in livertransplantrecipients with hepatitis B virus-related acute-on-chronic liver failure. This single-center retrospective study of early allograft dysfunction is based on data from January 2015 to June 2020 for 323 recipients with hepatitis B virus-related acute-on-chronic liver failure and 445 with only hepatitis B virus infection (control group). Data that correlated with early allograft dysfunction and outcome were analyzed. Incidence of early allograft dysfunction in patients with hepatitis B virus-related acute-on-chronic liver failure was significantly higher versus the control group (39.3% vs 21.1%; P < .001). Transplant recipients with hepatitis B virus-related acute-onchronic liver failure who developed early allograft dysfunction had lower 90-day, 180-day, and 360-day patient survival rates versus patients with no early allograft dysfunction (89.0% vs 98.0%, 82.7% vs 97.5%, and 80.3% vs 96.4%, respectively; P < .001). Pretransplant kidney failure (odds ratio, 2.644; 95% CI, 1.019-6.864; P = .046), pretransplant coagulation failure (odds ratio, 2.162; 95% CI, 1.291-3.621; P = .003), and operative time (odds ratio, 1.005; 95% CI, 1.002-1.008; P = .003) were independent risk factors for early allograft dysfunction in liver transplant recipients with hepatitis B virus-related acute-onchronic liver failure. There was a synergistic effect of early allograft dysfunction and preoperative kidney/coagulation failure on survival rates of liver transplant recipients with hepatitis B virus-related acute-on-chronic liver failure. Preoperative kidney/coagulation failure and operative time were independent risk factors of early allograft dysfunction in deceased donor liver transplant recipients with hepatitis B virus-related acute-on-chronic liver failure. The combination of early allograft dysfunction and preoperative kidney/coagulation failure was significantly associated with lower survival of these recipients.

Impact of different urinary tract infection phenotypes within the first year post-transplant on renal allograft outcomes

In this study, we investigated the clinical impact of different urinary tract infection (UTI) phenotypes occurring within the first year after renal transplantation. The population included 2368 transplantations having 2363 UTI events. Patients were categorized into four groups based on their compiled UTI events observed within the first year after transplantation: (i) no colonization or UTI (n = 1404; 59%), (ii) colonization only (n = 353; 15%), (iii) occasional UTI with 1–2 episodes (n = 456; 19%), and (iv) recurrent UTI with ≥3 episodes (n = 155; 7%). One‐year mortality and graft loss rate were not different among the four groups, but patients with recurrent UTI had a 7‐10 ml/min lower eGFR at year one (44 ml/min vs. 54, 53, and 51 ml/min; p < .001). UTI phenotypes had no impact on long‐term patient survival (p = .33). However, patients with recurrent UTI demonstrated a 10% lower long‐term death‐censored allograft survival (p < .001). Furthermore, recurrent UTI was a strong and independent risk factor for reduced death‐censored allograft survival in a multivariable analysis (HR 4.41, 95% CI 2.53–7.68, p < .001). We conclude that colonization and occasional UTI have no impact on pertinent outcomes, but recurrent UTI are associated with lower one‐year eGFR and lower long‐term death‐censored allograft survival. Better strategies to prevent and treat recurrent UTI are needed.

Evaluation of clotrimazole prophylaxis on tacrolimus trough concentrations in kidney transplant recipients.

BackgroundClotrimazole troches are used as prophylaxis against oropharyngeal candidiasis post‐transplant and have limited systemic absorption. Following several occurrences of tacrolimus concentration fluctuations after clotrimazole discontinuation, its use as prophylaxis was discontinued post‐kidney transplant.MethodsWe conducted a retrospective cohort study to evaluate the effect of clotrimazole prophylaxis on tacrolimus trough concentrations post‐kidney transplant. The study included adult patients who received a kidney transplant at Cleveland Clinic Main Campus from August 1, 2019 to July 1, 2020 and were maintained on per‐protocol, standard‐dose tacrolimus through 90 days post‐transplant. Patients were excluded if they received cyclosporine, systemic antifungals, strong CYP3A4 inhibitors or inducers, or a simultaneous multiorgan transplant. The primary objective was to compare tacrolimus trough concentrations before and after completion of clotrimazole prophylaxis. Secondary objectives were to compare the time to first post‐transplant goal tacrolimus trough concentration, the rate of for‐cause allograft biopsies within 90 days after transplant, and the incidence and type of candidiasis within 30 days after transplant, pre‐ and post‐protocol change.ResultsFollowing clotrimazole discontinuation, the median tacrolimus trough concentration decreased from 10.5 ng/ml (IQR 8.4–12.2) to 6.6 ng/ml (IQR 5–8.7, p < 0.0001). No statistically significant differences in the rate of for‐cause allograft biopsies (4.9% vs. 9.7%, p = 0.264) or incidence of candidiasis (1.2% vs. 5.4%, p = 0.217) were observed between those who received clotrimazole and those who did not receive clotrimazole.ConclusionsOur study provides further evidence of a significant drug–drug interaction between tacrolimus and clotrimazole among kidney transplant recipients that can potentially lead to negative allograft outcomes.

Impact of Carbapenem Peri-Transplant Prophylaxis and Risk of Extended-Spectrum Cephalosporin-Resistant Enterobacterales Early Urinary Tract Infection in Kidney Transplant Recipients: A Propensity Score-Matched Analysis.

BackgroundUrinary tract infection (UTI) is the most common bacterial infection after kidney transplantation (KT), leading to unfavorable clinical and allograft outcomes. Gram-negative uropathogenic bacteria are frequently encountered especially extended-spectrum cephalosporin-resistant (ESC-R) Enterobacterales (EB), causing UTI early after KT.MethodsA retrospective single transplant study was conducted between January 2016 and December 2019. We performed 1:1 nearest-neighbor propensity score matching without replacement using recipient age, recipient sex, induction, transplant year, human leukocyte antigen, cold ischemia time, and panel-reactive antibody before analyses. Cumulative incidence of ESC-R EB early (within 14 days after KT) UTI was estimated by the Kaplan–Meier method. Risk factors for ESC-R EB early UTI were analyzed by a Cox proportional hazards model. Variables measured after transplantation were considered time-dependent covariates.ResultsWe included 620 KT recipients (37% women; mean age ± SD, 43 ± 11 years). Overall, 64% and 76% received deceased-donor allograft and induction therapy. Sixty-five (10%) and 555 (90%) received carbapenems and cefuroxime peri-transplant prophylaxis, respectively. Early UTI occurred in 183 (30%) patients, 52% caused by ESC-R EB. Propensity score matching produced 65 well-balanced pairs. During a 14-day follow-up, the cumulative incidence of ESC-R EB early UTI was 5 and 28% in the carbapenems and cefuroxime groups, respectively (log-rank test = 0.003). Peri-transplant carbapenems prophylaxis was a protective factor against ESC-R EB after KT (hazard ratio, 0.19; 95% confidence interval, 0.05–0.64; p = 0.008). Clinical and allograft outcomes did not differ significantly between the groups.ConclusionsIn the setting where ESC-R EB UTI is common among KT recipients, carbapenems peri-transplant prophylaxis could protect against the occurrence of early ESC-R EB UTI after KT. Further prospective studies should focus on this specific infection prevention strategy.

Pediatric Kidney Transplantation-Can We Do Better? The Promise and Limitations of Epitope/Eplet Matching.

Kidney transplant is the optimal treatment for end-stage kidney disease as it offers significant survival and quality of life advantages over dialysis. While recent advances have significantly improved early graft outcomes, long-term overall graft survival has remained largely unchanged for the last 20 years. Due to the young age at which children receive their first transplant, most children will require multiple transplants during their lifetime. Each subsequent transplant becomes more difficult because of the development of de novo donor specific HLA antibodies (dnDSA), thereby limiting the donor pool and increasing mortality and morbidity due to longer time on dialysis awaiting re-transplantation. Secondary prevention of dnDSA through increased post-transplant immunosuppression in children is constrained by a significant risk for viral and oncologic complications. There are currently no FDA-approved therapies that can meaningfully reduce dnDSA burden or improve long-term allograft outcomes. Therefore, primary prevention strategies aimed at reducing the risk of dnDSA formation would allow for the best possible long-term allograft outcomes without the adverse complications associated with over-immunosuppression. Epitope matching, which provides a more nuanced assessment of immunological compatibility between donor and recipient, offers the potential for improved donor selection. Although epitope matching is promising, it has not yet been readily applied in the clinical setting. Our review will describe current strengths and limitations of epitope matching software, the evidence for and against improved outcomes with epitope matching, discussion of eplet load vs. variable immunogenicity, and conclude with a discussion of the delicate balance of improving matching without disadvantaging certain populations.

Long-Term Clinical Outcomes of Keratolimbal Allograft Alone or in Combination With Keratoplasty in Chronic and Delayed-Onset Mustard Gas Keratopathy.

The purpose of this study was to investigate the long-term clinical outcome of keratolimbal allograft (KLAL) alone or in combination with keratoplasty, in the management of patients with chronic and delayed-onset mustard gas keratopathy (MGK). Patients who had KLAL for MGK with or without corneal transplantation between 2002 and 2016 were recalled to be enrolled in this retrospective interventional case series. The primary outcome was the success rate of the KLAL demonstrated by Kaplan-Meier cumulative survival analysis. The secondary outcomes were postoperative BCVA and the need for further surgery. A total of 108 eyes of 68 patients with MGK underwent KLAL. All patients were male with an average age of 54 ± 6 years with an average follow-up duration of 81.9 ± 38.4 months. Sectoral KLAL alone was performed in 62 eyes (57.4%), combined with lamellar keratoplasty (LKP) in 40 eyes (37%) and combined with penetrating keratoplasty in 6 eyes (5.6%). The cumulative probability of success was 75% within the follow-up duration. The mean duration of successful KLAL survival was 80.6 ± 38 months. 88.1% of these eyes needed only 1 operation to stabilize the ocular surface. Average BCVA did not improve significantly after KLAL alone, except in those accompanied by keratoplasty. KLAL combined with LKP achieved the superior clinical outcome compared with KLAL alone. Infectious keratitis occurred in 6 eyes (5.5%). No adverse event due to postoperative systemic immunosuppression was observed. KLAL alone or combined with LKP is effective, durable, and visually acceptable in the reconstruction of ocular surface in patients with limbal stem cell deficiency secondary to MGK.

Donor Nephrectomy Through Mini-Flank Incision: A Single-Centre Experience Among Nigerian Patients.

Background and objectiveThe field of kidney transplantation in sub-Saharan Africa is still in the rudimentary stages. The majority of patients with chronic kidney disease have no access to renal replacement therapy, leading to very high mortality rates. Donor nephrectomy (DN) is an important aspect of kidney transplantation. Over the last two decades, open DN (ODN) has given way to minimally invasive techniques like laparoscopic DN (LDN) and robotic-assisted DN. In this study, we aimed to describe our experience with mini-flank incision donor nephrectomy (MIDN) at a Nigerian renal transplant center.Materials and methodsWe conducted a retrospective review of all DN cases performed at a single Nigerian kidney transplantation center over a three-year period. Information obtained from these patients was classified into pre-, intra-, and postoperative. The data included sociodemographic characteristics, preoperative preparation, details of intraoperative techniques, and postoperative findings. These were entered into a proforma and analyzed using SPSS Statistics version 21 (IBM Corp., Armonk, NY).ResultsA total of 230 patients underwent ODN during the study period. The majority of the donors were males (92.8%) with a mean age of 30.83 ±8.43 years. The body mass index (BMI) of most (76.1%) of the donors was within the normal range (18.5-24.9 kg/m2). The duration of DNs ranged from 72 to 154 minutes with a mean duration of 130 ±28 minutes. The length of flank incisions ranged from 7.8 to 12 cm with a mean incision length of 10.8 ±1.0 cm. Donors who had MIDN attained satisfactory postoperative pain control with about 90% of them having a BMI of <30 kg/m2. Oral intake and ambulation were commenced on the first postoperative day, and the cosmetic outcomes were deemed acceptable in over 90% of kidney donors.ConclusionMini-incision for DN through the flank approach is a suitable alternative to LDN in the developing world where facilities and skills for LDN or robotic nephrectomies are largely unavailable. It offers a short recovery time, early ambulation, and excellent allograft outcomes.

Poor Outcomes in Patients With Transplant Glomerulopathy Independent of Banff Categorization or Therapeutic Interventions.

BackgroundTransplant glomerulopathy (TG) may indicate different disease entities including chronic AMR (antibody-mediated rejection). However, AMR criteria have been frequently changed, and long-term outcomes of allografts with AMR and TG according to Banff 2017 have rarely been investigated.Methods282 kidney allograft recipients with biopsy-proven TG were retrospectively investigated and diagnosed according to Banff'17 criteria: chronic AMR (cAMR, n = 72), chronic active AMR (cAAMR, n = 76) and isolated TG (iTG, n = 134). Of which 25/72 (34.7%) patients of cAMR group and 46/76 (60.5%) of cAAMR group were treated with antihumoral therapy (AHT).ResultsUp to 5 years after indication biopsy, no statistically significant differences were detected among iTG, cAMR and cAAMR groups in annual eGFR decline (−3.0 vs. −2.0 vs. −2.8 ml/min/1.73 m2 per year), 5-year median eGFR (21.5 vs. 16.0 vs. 20.0 ml/min/1.73 m2), 5-year graft survival rates (34.1 vs. 40.6 vs. 31.8%) as well as urinary protein excretion during follow-up. In addition, cAMR and cAAMR patients treated with AHT had similar graft and patient survival rates in comparison with those free of AHT, and similar comparing with iTG group. The TG scores were not associated with 5-year postbiopsy graft failure; whereas the patients with higher scores of chronic allograft scarring (by mm-, ci- and ct-lesions) had significantly lower graft survival rates than those with mild scores. The logistic-regression analysis demonstrated that Banff mm-, ah-, t-, ci-, ct-lesions and the eGFR level at biopsy were associated with 5-year graft failure.ConclusionsThe occurrence of TG is closely associated with graft failure independent of disease categories and TG score, and the long-term clinical outcomes were not influenced by AHT. The Banff lesions indicating progressive scarring might be better suited to predict an unfavorable outcome.

MO953: Relevance of Proteinuria and Donor Specific Antibody in Kidney Transplanted Recipients and Allograft Outcomes

Abstract BACKGROUND AND AIMS The onset of proteinuria in renal allograft recipients is a frequent complication that may be associated with an increased risk of graft failure and mortality. Our aim was to research if proteinuria effects is independent from donor specific antibody (DSA) for transplant graft survival and the changes of proteinuria response to therapy in ABMR group. METHOD 85 transplanted patients were enrolled in our study and followed up till 31 October 2020 or till death, or date of return to dialysis. We created three groups: ABMR group (n = 19, biopsy proven antibody mediated rejection), ABMRDSApos positive group (n = 14) ABMRDSAneg (n = 5), DSA negative group with stabile kidney function without rejection as a reference (n = 52). Differences in patient, donor and transplant characteristics between DSA positive and negative groups were assessed by Fishers exact test for categorical variables. Death censored graft loss was assessed by Kaplan Meier analysis with log risk statistics. RESULTS Proteinuria decrease after treatment in ABMR group (P = 0.0009). Graft failure's frequency increase every 10 mg/mmol elevation of proteinuria means 7% elevation (hazard ratio: 1.07%). Before treatment nephrotic proteinuria was found in group AMBRDSApoz 21%, 14,29% in group ABMR DSAneg 1,92% in reference group. Estimated 3-year graft survival was 87, 5% in ABMR group, 93% in DSA pos group, and 100% in DSA negative group (log-rank probe P = 0.0666). CONCLUSION The presence of DSA increases graft loss but it is independent to proteinuria. Therapy refractory proteinuria state represents worse graft survival.