Positive Kidney Transplant Research Articles

406.2: Graft protein shows a distinct signature in donor-specific antibody positive kidney transplant recipients with antibody-mediated rejection.

406.2: Graft protein shows a distinct signature in donor-specific antibody positive kidney transplant recipients with antibody-mediated rejection.

Evaluation of the relationship between de-novo DSA development and CXCR5+PD-1+CD8+ T cells and PD-1/PD-L1 mRNA expression in kidney transplant recipients.

The relationship between the Follicular Cytotoxic T cell subgroup and expression levels of PD1/PD-L1 genes and the development of donor specific antibody (DSA) is unknown. In this study, we aimed to examine CD8+CXCR5+PD-1+ follicular cytotoxic T cell levels and expression levels of PD1/PD-L1 genes in peripheral blood lymphocytes in de-novo DSA positive and negative kidney transplant recipients (KTR). In our study, expression of PD-1/ PD-L1 genes by Real-Time Quantitative PCR method and CD8+CXCR5+PD-1+ T cell expression levels by flow cytometric method were obtained from peripheral blood samples. 63 participants were included in the study (de-novo DSA positive recipients (n=22, group 1), de-novo DSA negative recipients (n=20, group 2) and healthy control (n=21, group 3). All patients had negative PRA before kidney transplantation. Expression (%) levels of target cells were evaluated by flow cytometry method. IBM SPSS Statistics for Windows Version 22 and R.3.3.2 software were used to evaluate the data. The demographic data of the groups were similar. PD-1 mRNA expression was higher in de-novo DSA positive KTR than negative (respectively, 1.03±.29/.82±.15, p: .001). CD8+CXCR5+PD-1+ T cell expression levels were found to be higher in the de-novo DSA positive group than in the negative group and similar to the healthy group (respectively, 3.06±1.98/.52±.40, p:.001, 3.06±1.98/2.78±.59, p:.62). The percentage of CD8+CXCR5+PD-1+ expressing T cells was significantly lower in the HLA-Class II+ group than other groups (HLA CI/II/ I+II, respectively, 3.63±2.72/1.65±.50/3.68±1.67, p: .04). In our study, a significant relationship was found between DSA formation and PD-1 mRNA level and CD8+CXCR5+PD-1+ follicular cytotoxic T cell in KTR.

Nirmatrelvir/ritonavir treatment in SARS-CoV-2 positive kidney transplant recipients – a case series with four patients

BackgroundDespite vaccination coronavirus disease 2019 (COVID-19)-associated mortality caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains high in kidney transplant recipients. Nirmatrelvir is a protease inhibitor with activity against SARS-CoV-2. Nirmatrelvir reduces the risk for mortality and hospitalization, which is approved for treating adults at risk for severe disease. Nirmatrelvir is metabolized by the cytochrome P-450 (CYP) 3A4 isozyme CYP3A4 and is therefore co-administered with the irreversible CYP3A4 inhibitor ritonavir, which results in a drug interaction with tacrolimus. A limited number of patients with nirmatrelvir/ritonavir and tacrolimus therapy after kidney transplantation have been reported to date. It has been reported that tacrolimus was paused during the five-day nirmatrelvir/ritonavir therapy and subtherapeutic tacrolimus levels were observed after finishing nirmatrelvir/ritonavir in two patients. Therefore, optimization of tacrolimus dosing is urgently needed in transplant recipients receiving nirmatrelvir/ritonavir treatment.Case presentationHere, we present our first-hand experience with four patients receiving tacrolimus therapy following kidney transplantation and nirmatrelvir/ritonavir therapy due to COVID-19. Tacrolimus was paused during nirmatrelvir/ritonavir therapy in all patients, which resulted in stable therapeutic tacrolimus levels. Tacrolimus was continued directly after finishing nirmatrelvir/ritonavir to avoid subtherapeutic levels in the first patient treated. This patient received his usual tacrolimus maintenance dose, which resulted in toxic levels. Based on this observation, tacrolimus therapy was continued 24 h after finishing nirmatrelvir/ritonavir treatment at a reduced dose in the subsequent patients. In these patients, therapeutic to supratherapeutic tacrolimus levels were observed despite the therapeutic break and dose reduction.Discussion and conclusionsBased on altered CYP3A4 metabolism, tacrolimus levels have to be closely monitored after treatment with nirmatrelvir/ritonavir. Our study suggests that tacrolimus treatment should be paused during nirmatrelvir/ritonavir medication and be continued 24 h after completing nirmatrelvir/ritonavir therapy at a reduced dose and under close monitoring. Based on the limited number of patients in this study, results must be interpreted with caution.

Antibody acquisition after second and third SARS-CoV-2 vaccinations in Japanese kidney transplant patients: a prospective study

Kidney transplant patients have lower antibody acquisition after SARS-CoV-2 vaccination. The efficacy of vaccines in Japanese kidney transplant patients with specific characteristics, such as predominant living-donor, ABO-incompatible kidney transplant, and low-dose immunosuppression, requires verification. We conducted a prospective study to estimate anti-SARS-CoV-2 antibody levels in 105 kidney transplant patients and 57 controls. Blood samples were obtained before vaccination, 1, 3, and 6months after second vaccination, and 1month after third vaccination. We investigated antibody acquisition rates, antibody levels, and factors associated with antibody acquisition. One month after second vaccination, antibody acquisition was 100% in the controls but only 36.7% in the kidney transplant group (P < 0.001). Antibody levels in positive kidney transplant patients were also lower than in the controls (median, 4.9 arbitrary units vs 106.4 arbitrary units, respectively, P < 0.001). Years after kidney transplant (odds ratio 1.107, 95% confidence interval 1.012-1.211), ABO-incompatible kidney transplant (odds ratio 0.316, 95% confidence interval 0.101-0.991) and mycophenolate mofetil use (odds ratio 0.177, 95% confidence interval 0.054-0.570) were significant predictors for antibody acquisition after second vaccination. After third vaccination, antibody positivity in the kidney transplant group increased to 75.3%, and antibody levels in positive patients were 71.7 arbitrary units. No factors were associated with de novo antibody acquisition. In Japanese kidney transplant patients, years after kidney transplant, ABO-incompatible kidney transplant and mycophenolate mofetil use were predictors for antibody acquisition after second vaccination. Third vaccination improves antibody status even in patients who were seronegative after the second vaccination.

Low dose thymoglobulin versus basiliximab in cytomegalovirus positive kidney transplant recipients: Effectiveness of preemptive cytomegalovirus modified strategy

BackgroundWe performed a retrospective trial to determine asymptomatic CMV reactivation and CMV disease in kidney allograft recipients with positive CMV serostatus. MethodsPreemptive modified strategy under low dose thymoglobulin versus basiliximab induction was evaluated. Patients were monitored by CMV-polymerase chain reaction (PCR); if the viral load was >4000copies/μl, they received valganciclovir adjusted for their renal function. Results132 recipients were included in the study, 84 and 48 receiving basiliximab and thymoglobulin induction respectively, and followed up for 12 months. Asymptomatic CMV reactivation was significantly higher for thymoglobulin (77.1% vs. 16.7%, p<0.001). Treatment groups had similar rates of CMV disease (3.6% vs. 2.1%, p 0.538). The significant difference in asymptomatic CMV reactivation between two treatment groups did not have any impact on 1 year graft function (71±26ml/min vs. 74±19ml/min; p=0.475) and no histological differences in protocol biopsies were observed among patients with asymptomatic CMV reactivation vs those without CMV reactivation. ConclusionsDue to the high asymptomatic CMV reactivation incidence in patients who received thymoglobulin induction, our results suggest that valganciclovir prophylaxis may be advantageous in CMV seropositive renal transplant recipients after low dose thymoglobulin induction. A preemptive strategy appeared to significantly reduce the likelihood of CMV disease in both groups. Rejection risk and negative impact in renal function associated with asymptomatic CMV reactivation was not found in our series.

210.7: Undetectable Recipient COVID-19 Plasma PCR Following COVID-19 Positive Donor Kidney Transplant: Proof of Concept Analysis

Introduction: With one-third of the United States still not fully vaccinated for COVID-19 and almost one-half unvaccinated in Arkansas, it is common to see patients presenting with non-survivable diagnosis, incidentally testing COVID-19+ or with recent history of mild COVID-19 infection. In the absence of COVID-19, such patients could become organ donors. Limited case series have demonstrated no COVID-19 syndrome following transplantation from such donors. However, hematogenous asymptomatic transmission of the COVID-19 virus following transplant remains unclear. Aim of this study was to assess COVID-19 virus presence in the recipient’s bloodstream at the early post-transplant period following COVID-19+ organ transplantation. Methods: An institutional protocol was drafted for the use of COVID-19+ donor organs. Eligible donors included those test COVID-19+, however with cause of death not related to COVID-19, and no evidence of moderate to severe COVID-19. Eligible recipients included those who tested negative for COVID-19 at the time of transplant, had been fully vaccinated against COVID-19, and consented to receive such organs. A protocol deviation occurred when a COVID-19+ organ was transplanted into a non-vaccinated recipient with recent history of resolved COVID-19 infection. Plasma was drawn to test for COVID-19 polymerase chain reaction (PCR) prior to hospital discharge post-transplant. All recipients received tixagevimab-cilgavimab (Evusheld) after plasma COVID-19 PCR testing. Results: Six recipients underwent kidney transplantation from COVID-19+ donors. One donor had reported mild symptoms of COVID-19 prior to hospitalization. Two donors tested Hepatitis C positive by nucleic amplification testing. 83.3% (N=5) of recipients were fully vaccinated prior to transplant (Table 1). An additional recipient had not been vaccinated but had history of recent COVID-19 infection. None of the recipients developed COVID-19 symptoms post-transplant. All had undetectable serum plasma COVID-19 PCR prior to discharge (testing range post-operative day 2 to 5). Post-transplant median length of stay was 3 days. Median follow-up was 39 days (33, 62). Two recipients had delayed renal allograft function. One patient developed antibody-mediated rejection diagnosed on post-operative day 30. No recipients required post-transplant testing for suspected COVID-19 symptoms. There was no mortality (Table 2). Discussion: This case series provides proof of concept that there is no evidence of hematogenous transfer of COVID-19 from donor positive organs to recipients immune to the virus. Therefore, otherwise transplantable organs from donors incidentally diagnosed with COVID-19 at the time of donation, with no indication of severe COVID-19 disease at the time of donation, should be considered for non-thoracic organ transplantation to suitable recipients, after appropriate consenting.

P16.08: COVID-19 Positive Kidney Transplant Recipients Behave Differently Compared to Non-transplant Patients ICU: Single Center Experience

P16.08: COVID-19 Positive Kidney Transplant Recipients Behave Differently Compared to Non-transplant Patients ICU: Single Center Experience

Occurrence of De novo Donor-Specific Antibodies After COVID-19 in Kidney Transplant Recipients Is Low Despite Immunosuppression Modulation

IntroductionDecreased immunosuppression has been proposed for kidney transplant recipients infected with coronavirus disease 2019 (COVID-19), but the impact on the alloreactive immune response during and after infection has been poorly investigated. We evaluated the occurrence of antihuman leukocyte antigen (HLA) donor-specific antibodies (DSAs) (post–COVID-19) and rejection episodes after COVID-19 with particular focus on immunosuppression modulation.MethodsKidney transplant recipients from 2 French institutions had anti-HLA antibody screening before and after COVID-19. Management of immunosuppression, rejection episodes, COVID-19 severity, inflammatory markers, and antiviral therapies were recorded.ResultsFrom 251 recruited patients, 72 were excluded because of COVID-19–related death (n = 25) and incomplete immunologic follow-up (n = 47). Among the remaining 179 included patients, almost half were hospitalized (49.2%). Antimetabolites were interrupted in 47% of patients (82% in hospitalized, median time of resumption of 23 days and in 15% nonhospitalized, median time of resumption of 7 days). Calcineurin inhibitors were interrupted in 12% of patients (all hospitalized, median time of resumption of 11 days). The incidence of post–COVID-19 DSA was 4% (8% and 0% in hospitalized and nonhospitalized, respectively). Allograft rejection occurred in 3 patients (1.7%) and all were hospitalized. Younger age, transplantation <1 year, and preexisting DSA were more frequently observed in patients with post–COVID-19 DSA, whereas inflammatory markers, lymphopenia, and use of antiviral therapies were not.ConclusionThe incidence of post–COVID-19 DSA among COVID-19–positive kidney transplant recipients was low (4%) despite a significant decrease in immunosuppression and was mainly restricted to high-risk immunologic patient’s status. COVID-19 severity was not associated with post–COVID-19 DSA and/or rejection.

Imlifidase-generated Single-cleaved IgG: Implications for Transplantation.

Background.Imlifidase is an immunoglobulin G (IgG)-specific protease conditionally approved in the EU for desensitization in highly sensitized crossmatch positive kidney transplant patients. Imlifidase efficiently cleaves both heavy chains of IgG in a 2-step process. However, low levels of the intermediate cleavage product, single-cleaved IgG (scIgG), may persist in the circulation. The study objective was to investigate Fc-mediated effector functions of scIgG and its potential impact on common clinical immunologic assays used to assess transplant eligibility.Methods.Imlifidase-generated scIgG, obtained by in vitro cleavage of HLA-sensitized patient serum or selected antibodies, was investigated in different complement- and FcγR-dependent assays and models, including clinical tests used to evaluate HLA-specific antibodies.Results.ScIgG had significantly reduced Fc-mediated effector function compared with intact IgG, although some degree of activity in complement- and FcγR-dependent models was still detectable. A preparation of concentrated scIgG generated from a highly HLA-sensitized individual gave rise to a positive signal in the anti-HLA IgG LABScreen, which uses anti-Fc detection, but was entirely negative in the C1qScreen. The same high-concentration HLA-binding scIgG preparation also generated positive complement-dependent cytotoxicity responses against 80%–100% of donor T and B cells, although follow-up titrations demonstrated a much lower intrinsic activity than for intact anti-HLA IgG.Conclusions.ScIgG has a significantly reduced capacity to mediate Fc-dependent effector functions. However, remaining HLA-reactive scIgG in plasma after imlifidase treatment can cause positive assay results equivalent to intact IgG in clinical assays. Therefore, complete IgG cleavage after imlifidase treatment is essential to allow correct decision-making in relation to transplant eligibility.

A multicenter evaluation of hepatitis B reactivation with and without antiviral prophylaxis after kidney transplantation.

Hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)-negative and hepatitis B core antibody (anti-HBc)-positive kidney transplant recipients ranges between 1.4% and 9.6%. Limited evidence is available regarding routine antiviral prophylaxis and identifiable risk factors for HBV reactivation in this population. In this multicenter retrospective study, we evaluated the prevalence of HBV reactivation in HBsAg-negative anti-HBc-positive kidney transplant recipients who did or did not receive antiviral prophylaxis. The primary outcome assessed the prevalence of HBV reactivation, defined as a positive HBV DNA by PCR of any viral load at or above the minimal detection level. The principal safety outcomes assessed 1-year graft survival, 1-year all-cause mortality, biopsy-proven acute rejection, and antibody-mediated rejection. One hundred and sixty-one patients met inclusion criteria and comprised two groups, antiviral prophylaxis (n=14) and no antiviral prophylaxis (n=147). Of patients who did not receive prophylaxis, only five (3.4%) experienced HBV reactivation, whereas one (7.1%) patient in the prophylaxis group experienced reactivation over a median follow-up of 1103 days (p=.43). Furthermore, there were no differences with respect to all secondary outcomes. Statistical analysis demonstrated delayed graft function to be a significant factor associated with HBV reactivation. These study results suggest that the prevalence of HBV reactivation in HBsAg-negative anti-HBc-positive kidney transplant recipients is low, regardless of antiviral prophylaxis. Furthermore, there were no significant graft-related outcomes among those that did experience reactivation.

Low dose thymoglobulin versus basiliximab in cytomegalovirus positive kidney transplant recipients: Effectiveness of preemptive cytomegalovirus modified strategy

BackgroundWe performed a retrospective trial to determine asymptomatic CMV reactivation and CMV disease in kidney allograft recipients with positive CMV serostatus. MethodsPreemptive modified strategy under low dose thymoglobulin versus basiliximab induction was evaluated. Patients were monitored by CMV-polymerase chain reaction (PCR); if the viral load was >4000copies/μl, they received valganciclovir adjusted for their renal function. Results132 recipients were included in the study, 84 and 48 receiving basiliximab and thymoglobulin induction respectively, and followed up for 12 months. Asymptomatic CMV reactivation was significantly higher for thymoglobulin (77.1% vs. 16.7%, p<0.001). Treatment groups had similar rates of CMV disease (3.6% vs. 2.1%, p 0.538). The significant difference in asymptomatic CMV reactivation between two treatment groups did not have any impact on 1 year graft function (71±26ml/min vs. 74±19ml/min; p=0.475) and no histological differences in protocol biopsies were observed among patients with asymptomatic CMV reactivation vs those without CMV reactivation. ConclusionsDue to the high asymptomatic CMV reactivation incidence in patients who received thymoglobulin induction, our results suggest that valganciclovir prophylaxis may be advantageous in CMV seropositive renal transplant recipients after low dose thymoglobulin induction. A preemptive strategy appeared to significantly reduce the likelihood of CMV disease in both groups. Rejection risk and negative impact in renal function associated with asymptomatic CMV reactivation was not found in our series.

A Programmatic Response, Including Bamlanivimab or Casirivimab-imdevimab Administration, Reduces Hospitalization and Death in COVID-19 Positive Abdominal Transplant Recipients.

(COVID-19) has resulted in significant morbidity and mortality in solid organ transplant recipients. In December 2020, at the peak of the Los Angeles outbreak, our center rapidly implemented a protocol to improve outpatient management and provide bamlanivimab or casirivimab-imdevimab [COVID monoclonal antibody (mAb) therapies] to all eligible COVID-19 positive liver and kidney transplant recipients. A retrospective review of all abdominal organ transplant recipients who were COVID-19 polymerase chain reaction positive between February 2020 and February 2021 from our center was performed. Patient demographics, COVID-19 treatments, hospitalizations, and survival were reviewed. Patients were considered eligible for COVID mAb therapy if they met outpatient criteria at the time of diagnosis. In the study period, 121 patients in the kidney transplant recipients group (KG) and 105 patients in the liver or combined liver/kidney transplant recipients group (LG) were COVID-19 polymerase chain reaction positive. Hospitalization rates were similar for the KG (45%) versus LG (35%) (P = 0.20), but mortality was higher for the KG (22%) when compared to LG (10%) (P = 0.02). Our programmatic response, including outpatient COVID mAb therapies, reduced hospitalizations (P = 0.01) and deaths (P = 0.01). Ninety-four KG and 87 LG patients were identified as potentially eligible for COVID mAb therapy, and 17 KG and 17 LG patients were treated. COVID mAb therapies reduced hospitalization from 32% to 15% (P = 0.045) and eliminated mortality (13% versus 0%, P = 0.04). An aggressive approach including outpatient COVID mAb therapy in the COVID positive abdominal organ transplant recipients significantly decreased hospitalization and death. Early outpatient intervention for COVID-19 disease in transplant patients should be considered where possible.

Casirivimab-Imdevimab (REGN-COV2) for Mild to Moderate SARS-CoV-2 Infection in Kidney Transplant Recipients

Casirivimab-Imdevimab (REGN-COV2) for Mild to Moderate SARS-CoV-2 Infection in Kidney Transplant Recipients

A machine learning framework for predicting long-term graft survival after kidney transplantation

Kidney transplantation (KT) is an optimal treatment for end-stage renal disease (ESRD). Currently, short-term KT outcomes are indeed excellent, but long-term successful outcomes are still difficult to achieve, and improving them is crucial for kidney recipients. An early and accurate prediction of long-term graft survival helps healthcare practitioners to create a more personalized treatment plans for patients and facilitates the performance of clinical trials. In this study, we propose a machine learning framework to early predict graft survival after five years of KT and determine the most influential parameters that affect the survival. Our dataset was collected from Charles Nicolle Hospital in Tunis in Tunisia and it included pre, peri, post KT aspects. We utilized four machine learning algorithms to select the most important features: the least absolute shrinkage and selection operator logistic regression (Lasso-LR), Random Forrest (RF), Decision Tree (DT), and Chi-square (Chi-sq). We utilized three Scikit-learn functions to implement those algorithms: SelectFromModel (SFM), Recursive Feature Elimination (RFE), and SelectKBest (SKB). Five algorithms were utilized to builds prediction models based on the data groups resulted from the feature selection step: logistic regression (LR), k-nearest neighbors (KNN), extreme gradient boosting (XGB), and artificial neural network (ANN). We evaluated the models using five performance measures: accuracy, sensitivity, specificity, F1 measure, and area under the curve (AUC). XGBoost resulted the best model with the highest AUC (89.7%). It was based ten features selected by RF algorithm and SFM function. The accuracy, sensitivity, specificity, and F1 of the best model were 91.5%, 91.9%, 87.5%, and 89.6%, respectively. This study proposes a novel approach for investigating long-term allograft survival while considering the complex relationship between all KT aspects and long-term outcomes. Our framework can be used as a decision support system for Nephrologists to early detect graft status, which helps in developing safer recommendations for kidney patients and consequently obtaining positive KT outcomes and mitigating the risks of graft failure.

Better outcome of COVID-19 positive kidney transplant recipients during the unremitting stage with optimized anticoagulation and immunosuppression.

IntroductionCOVID‐19 is an ongoing pandemic with high morbidity and mortality and with a reported high risk of severe disease in kidney transplant recipients (KTR).AimWe aimed to report the largest number of COVID‐19‐positive cases in KTR in a single center and to discuss their demographics, management, and evolution.MethodsWe enrolled all the two thousand KTR followed up in our center in Kuwait and collected the data of all COVID‐19‐positive KTR (104) from the start of the outbreak till the end of July 2020 and have reported the clinical features, management details, and both patient and graft outcomes.ResultsOut of the one hundred and four cases reported, most of them were males aged 49.3 ± 14.7 years. Eighty‐two of them needed hospitalization, of which thirty‐one were managed in the intensive care unit (ICU). Main comorbidities among these patients were hypertension in 64.4%, diabetes in 51%, and ischemic heart disease in 20.2%. Management strategies included anticoagulation in 56.7%, withdrawal of antimetabolites in 54.8%, calcineurin inhibitor (CNI) withdrawal in 33.7%, the addition of antibiotics in 57.7%, Tocilizumab in 8.7%, and antivirals in 16.3%. During a follow‐up of 30 days, the reported number of acute kidney injury (AKI) was 28.7%, respiratory failure requiring oxygen therapy 46.2%, and overall mortality rate was 10.6% with hospital mortality of 13.4% including an ICU mortality rate of 35.5%.ConclusionBetter outcome of COVID‐19‐positive KTR in our cohort during this unremitting stage could be due to the younger age of patients and early optimized management of anticoagulation, modification of immunosuppression, and prompt treatment of secondary bacterial infections. Mild cases can successfully be managed at home without any change in immunosuppression.

Impact of Protease Inhibitor-Based Antiretroviral Therapy on Tacrolimus Intrapatient Variability in HIV-Positive Kidney Transplant Recipients

BackgroundHuman immunodeficiency virus (HIV)-positive kidney transplant (KT) recipients have been shown to experience higher rejection rates due in part to drug-drug interactions between antiretroviral therapy (ART) and immunosuppression regimens. High tacrolimus (FK) intrapatient variability (IPV) is associated with inferior outcomes in KT. The purpose of this study was to determine the impact of protease inhibitor (PI)-based ART on FK IPV and graft outcomes. MethodsWe performed a single-center review of HIV-positive KT recipients from 2007 to 2017. Percentage coefficient of variation (%CV = (σ/μ) × 100; σ, median; μ, standard deviation) was calculated for FK IPV. FK IPV at 6 and 12 months, graft function, and immune outcomes in PI-based vs non-PI-based KT recipients were compared. ResultsA total of 23 HIV-positive KT patients were identified, of whom 10 were maintained on PI-based ART. Median IPV for the entire cohort at 6 and 12 months was 35.8% and 41%, respectively. Patients on PI-based regimens were proportionally more likely to experience high IPV at both time points. Median FK IPV was numerically higher at 6 months (37.3% vs 26.8%, P = .11) and significantly higher at 12 months (57.8% vs 30.9%, P = .01) for patients on PI-based regimens. Lastly, inferior graft function was observed in PI-based patients. ConclusionOur data suggest that PI-based ART is associated with a higher degree of FK IPV, which may contribute to worsening graft function. Larger studies are warranted to determine the impact of PI-based ART on FK IPV and graft outcomes in this population.

Evidence of potent humoral immune activity in COVID-19-infected kidney transplant recipients.

Whether kidney transplant recipients are capable of mounting an effective anti‐severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) adaptive immune response despite chronic immunosuppression is unknown and has important implications for therapy. Herein, we analyzed peripheral blood cell surface and intracellular cytokine phenotyping by flow cytometry along with serum antibody testing in 18 kidney transplant recipients with active coronavirus disease 2019 (COVID‐19) infection and 36 matched, transplanted controls without COVID‐19. We observed significantly fewer total lymphocytes and fewer circulating memory CD4+ and CD8+ T cells in the COVID‐19 subjects. We also showed fewer anergic and senescent CD8+ T cells in COVID‐19 individuals, but no differences in exhausted CD8+ T cells, nor in any of these CD4+ T cell subsets between groups. We also observed greater frequencies of activated B cells in the COVID‐19 patients. Sixteen of 18 COVID‐19 subjects tested for anti‐SARS‐CoV‐2 serum antibodies showed positive immunoglobulin M or immunoglobulin G titers. Additional analyses showed no significant correlation among immune phenotypes and degrees of COVID‐19 disease severity. Our findings indicate that immunosuppressed kidney transplant recipients admitted to the hospital with acute COVID‐19 infection can mount SARS‐CoV‐2‐reactive adaptive immune responses. The findings raise the possibility that empiric reductions in immunosuppressive therapy for all kidney transplant recipients with active COVID‐19 may not be required.

Hepatitis B reactivation after kidney transplantation in hepatitis B surface antigen-negative, core antibody-positive recipients.

Nowadays, intensive immunosuppressive therapy including rituximab is commonly used prior to kidney transplantation (KT), raising concerns over hepatitis B virus (HBV) reactivation among hepatitis B surface antigen (HBsAg)-negative and anti-hepatitis B core (HBc)-positive KT recipients. Recent practice guidelines suggested watchful monitoring or antiviral prophylaxis for the first 6-12months, the period of maximal immunosuppression. However, the actual risk for HBV reactivation, and whether short-term antiviral therapy in the early period is necessary, remains unclear. A total of 449 HBsAg-negative and anti-HBc-positive KT recipients were analysed for HBV reactivation. During a median follow-up of 6.7 (interquartile range: 4.2-9.4) years, HBV reactivation was observed in 9 patients (2.0%). The median time of HBV reactivation from KT was 2.8years (range: 1.4-11.5years), with cumulative incidence rates of 0%, 1% and 2% for 1, 3 and 5years, respectively. There were no severe adverse outcomes, including liver transplantation or mortality related to HBV reactivation. The risk of HBV reactivation was not high, even in anti-HBs-negative patients (n=60, 4% at 5years), ABO mismatch (n=92, 4% at 5years), use of rituximab (n=66, 3% at 5years) or plasmapheresis (n=17, 7% at 5years), and acute rejection (n=169, 3% at 5years). In conclusion, the HBV reactivation risk was not high and the time of detection was not clustered in the early post-KT period. Our findings favour continued watchful monitoring over antiviral prophylaxis in the early period.

Long term renal safety of HCV direct acting antivirals in HCV positive kidney transplant recipients

Introduction and aim: General transplant outcome of HCV kidney transplant recipients (KTRs) is worse than that of non-infected one. Direct acting antivirals (DAAs) resulted efficacious also in KTRs. Drug interactions between Calcineurin inhibitors (CNI) and DAAs had been described. Immunological rejection is the Achilles heel of kidney transplantation. Thus, the impact of DAAs on CNI levels and the effect on renal function need to be evaluated.

Circulating de novo Donor Specific Antibodies and Carotid Intima-media Thickness in Pediatric Kidney Transplant Recipients, A Pilot Study.

Background: The presence of circulating de novo donor specific anti-HLA antibodies (dnDSA) has been implicated in an immune-mediated form of accelerated systemic arteriosclerosis in adult heart and kidney transplant recipients, however this has not been previously investigated in pediatric kidney transplant recipients. Carotid intima-media thickness (CIMT) is a reliable method for detection of arteriosclerosis. We hypothesized that children who develop dnDSA after kidney transplant would have increased CIMT compared with those who remain dnDSA negative.Methods: A prospective, controlled pilot cohort study of 38 transplant patients and 20 healthy controls was conducted to investigate the association between CIMT and development of dnDSA after kidney transplant. CIMT, anthropometrics, blood pressure and lipid panel were measured at 1, 18, and 30 months post-transplant. DSA was checked at 6, 12, 18, 24 and 30 months post-transplant. CIMT of DSA positive transplant recipients was compared to DSA negative and controls.Results: Of the 38 transplant recipients, 7 patients developed dnDSA by 18–30 months post-transplant. Among 5 dnDSA positive patients who did not receive treatment for DSA prior to CIMT measurement (n=6 observations), the median CIMT was 0.505 mm (95% CI 0.454–0.560 mm) at 18–30 months post-transplant, compared to 0.455 mm (95% CI 0.440–0.470) in DSA negative transplant recipients (n = 54 observations of 30 patients) and 0.450 mm (95% CI 0.436–0.460) in the healthy controls (20 observations of 20 patients). Presence of dnDSA was independently associated with a 7.8% increase in CIMT compared to those without dnDSA (p=0.006), after adjusting for race, hypertension, dyslipidemia, and abdominal obesity.Conclusions: Development of dnDSA was associated with increased CIMT, an indicator of arteriosclerosis, in a cohort of dnDSA positive pediatric kidney transplant recipients. The association between dnDSA and CIMT was independent of traditional CV risk factors, including hypertension, dyslipidemia, and abdominal obesity.