Kidney transplantation after pelvic radiotherapy: increased morbidity?

INTRODUCTION: The impact of pelvic irradiation on kidney transplant surgery is still unclear. The main objective of our study is to evaluate the feasibility and the saftety of renal transplantation following pelvic radiotherapy. METHODS: We collected characteristics and kidney transplant data from patients with a history of pelvic cancer treated with pelvic irradiation between 2005 and 2021. These data were collected via the prospective information system "Computerized Data Validated in Transplantation" (DIVAT) and medical records. We carried out a comparative study with a non-irradiated matched control group to compare the data of intraoperative surgeries, complications reported postoperatively as well as survival of the graft and the patient. Patients were matched on age, sex, side of graft implantation, and graft rank. RESULTS: 24 patients were collected with an average age of 65, 18 patients were treated for prostatic adenocarcinoma, 4 for gynecological cancer and 2 testicular cancers. 21 patients were treated by radiotherapy, 3 by brachytherapy. 8 patients had a target dose on the iliac lymph nodes. The comparative study showed a significant difference in operative difficulty (n=15 versus n=1 p<0.01), operative duration (190min versus 149min p=0.005), occurrence of lymphocele (p=0.041). Urinary anastomosis surgical techniques were different, 83.3% of control patients had a ureterovesical anastomosis against 58.3% of patients with a history of irradiation (p=0.057) and about 29% of irradiated patients had an uretero-ureteral anastomosis. There was no other significant difference in per and postoperative criteria or survival. DISCUSSION: A history of pelvic irradiation significantly increases the technical complexity of kidney transplantation without impacting saftey and kidney graft survival.An history of Pelvic irradiation should not be a contraindication to kidney transplant.

Toward an optimization of empirical antibiotic therapy in acute graft pyelonephritis: A retrospective multicenter study.

OBJECTIVE: Acute graft pyelonephritis (AGPN) is the most frequent infectious complication in kidney transplant recipients (KTR). The treatment of acute community-acquired (CA) pyelonephritis is based on third-generation cephalosporins (3GC) and fluoroquinolones. Cefepime or a piperacillin-tazobactam combination are more often used in healthcare-associated (HCA) infections. However, these recommendations do not consider the resistance observed in KTRs. The objective of our study was to define the most appropriate empirical antibiotherapy for AGPN in KTRs according to the CA and HCA settings. To answer this question, we assessed the prevalence of resistance to different antibiotics usually recommended for urinary tract infections (UTIs) in the general population. METHODS: Observational, retrospective, multicenter study covering all episodes of AGPN occurring in hospitalized KTRs in 2019. RESULTS: A total of 210 patients were included in 7 centers and 244 episodes of AGPN were analyzed (158 CA-AGPN and 86 HCA-AGPN). The prevalence of 3GC and fluoroquinolone resistance was 23 % (n = 36) and 30 % (n = 50) in CA infections (n = 158), and 47 % (n = 40) and 31 % (n = 27) in HCA infections (n = 86), respectively. Cefepime resistance rate was 19 % (n = 30) in CA-AGPN and 29 % (n = 25) in HCA-AGPN. Piperacillin-tazobactam combination had resistance rates > 15 % in both CA and HCA infections. The only antimicrobials with resistance rates < 10 % were aminoglycosides and carbapenems. CONCLUSION: None of the antibiotics recommended in empirical treatment in UTIs has shown a resistance rate of less than 10% with regard to AGPN. Therefore, none of them should be used as monotherapy. A combination therapy including amikacin could be an appropriate strategy in this setting.

Impact of Preformed Donor-Specific Anti-HLA-Cw and Anti-HLA-DP Antibodies on Acute Antibody-Mediated Rejection in Kidney Transplantation.

Given the risk of rejection, the presence of preformed donor specific antibodies (DSA) contraindicates transplantation in most allocation systems. However, HLA-Cw and -DP DSA escape this censorship. We performed a multicentric observational study, in which the objective was to determinate risk factors of acute antibody-mediated rejection (aABMR) in recipients transplanted with preformed isolated Cw- or DP-DSA. Between 2010 and 2019, 183 patients were transplanted with a preformed isolated Cw- or DP-DSA (92 Cw-DSA; 91 DP-DSA). At 2 years, the incidence of aABMR was 12% in the Cw-DSA group, versus 28% in the DP-DSA group. Using multivariable Cox regression model, the presence of a preformed DP-DSA was associated with an increased risk of aABMR (HR = 2.32 [1.21-4.45 (p = 0.001)]) compared with Cw-DSA. We also observed a significant association between the DSA's MFI on the day of transplant and the risk of aABMR (HR = 1.09 [1.08-1.18], p = 0.032), whatever the DSA was. Interaction term analysis found an increased risk of aABMR in the DP-DSA group compared with Cw-DSA, but only for MFI below 3,000. These results may plead for taking these antibodies into account in the allocation algorithms, in the same way as other DSA.

Kidney allograft rejection is associated with an imbalance of B cells, regulatory T cells and differentiated CD28-CD8+ T cells: analysis of a cohort of 1095 graft biopsies.

Introduction: The human immune system contains cells with either effector/memory or regulatory functions. Besides the well-established CD4+CD25hiCD127lo regulatory T cells (Tregs), we and others have shown that B cells can also have regulatory functions since their frequency and number are increased in kidney graft tolerance and B cell depletion as induction therapy may lead to acute rejection. On the other hand, we have shown that CD28-CD8+ T cells represent a subpopulation with potent effector/memory functions. In the current study, we tested the hypothesis that kidney allograft rejection may be linked to an imbalance of effector/memory and regulatory immune cells. Methods: Based on a large cohort of more than 1000 kidney graft biopsies with concomitant peripheral blood lymphocyte phenotyping, we investigated the association between kidney graft rejection and the percentage and absolute number of circulating B cells, Tregs, as well as the ratio of B cells to CD28-CD8+ T cells and the ratio of CD28-CD8+ T cells to Tregs. Kidney graft biopsies were interpreted according to the Banff classification and divided into 5 biopsies groups: 1) normal/subnormal, 2) interstitial fibrosis and tubular atrophy grade 2/3 (IFTA), 3) antibody-mediated rejection (ABMR), 4) T cell mediated-rejection (TCMR), and 5) borderline rejection. We compared group 1 with the other groups as well as with a combined group 3, 4, and 5 (rejection of all types) using multivariable linear mixed models. Results and discussion: We found that compared to normal/subnormal biopsies, rejection of all types was marginally associated with a decrease in the percentage of circulating B cells (p=0.06) and significantly associated with an increase in the ratio of CD28-CD8+ T cells to Tregs (p=0.01). Moreover, ABMR, TCMR (p=0.007), and rejection of all types (p=0.0003) were significantly associated with a decrease in the ratio of B cells to CD28-CD8+ T cells compared to normal/subnormal biopsies. Taken together, our results show that kidney allograft rejection is associated with an imbalance between immune cells with effector/memory functions and those with regulatory properties.

[Surgical outcomes and complications following third kidney transplantation]. / Résultats et complications chirurgicales des troisièmes transplantations rénales.

BACKGROUND: After two consecutive kidney transplant failures, a third kidney transplantation improves survival for patients on the waiting list. The surgical outcomes and complications of third kidney transplantations remain poorly known. METHODS: We analyzed the last 100 third kidney transplantations performed in our center between January 2000 and August 2018. The data, relating to donors and recipients, were extracted retrospectively from medical records and from the prospective DIVAT database (computerized and validated data in transplantation). Continuous variables are expressed as means, medians, first and third quartiles (median, [Q1;Q3]). Categorical variables are expressed as percentages. Patient and transplant survivals were calculated using the Kaplan-Meier method. RESULTS: Mean age of recipients was 46.4 years (47, [36;53]). Thirty-five percent had kidney failure due to urinary tract malformations. Mean age of donors was 48.2 years (52, [39.75; 58]) with 63% of donors with standard criteria. Mean cold ischemia time was 22.4hours (21, [16.5; 29.2]). Surgical mortality rate was 2% and surgical complication rate was 45%. Third kidney transplants survival was 73.1% and 58.8% at 5 years and 10 years. Mortality rate with a functioning transplant was 18%. CONCLUSION: A third kidney transplant offers satisfactory functional outcomes but remains associated with high morbi-mortality and a significant death rate with a functioning transplant.

Subclinical rejection-free diagnostic after kidney transplantation using blood gene expression.

We previously established a six-gene-based blood score associated with operational tolerance in kidney transplantation which was decreased in patients developing anti-HLA donor-specific antibodies (DSA). Herein, we aimed to confirm that this score is associated with immunological events and risk of rejection. We measured this using quantitative PCR (qPCR) and NanoString methods from an independent multicenter cohort of 588 kidney transplant recipients with paired blood samples and biopsies at one year after transplantation validating its association with pre-existing and de novo DSA. From 441 patients with protocol biopsy, there was a significant decrease of the score of tolerance in 45 patients with biopsy-proven subclinical rejection (SCR), a major threat associated with pejorative allograft outcomes that prompted an SCR score refinement. This refinement used only two genes, AKR1C3 and TCL1A, and four clinical parameters (previous experience of rejection, previous transplantation, sex of recipient and tacrolimus uptake). This refined SCR score was able to identify patients unlikely to develop SCR with a C-statistic of 0.864 and a negative predictive value of 98.3%. The SCR score was validated in an external laboratory, with two methods (qPCR and NanoString), and on 447 patients from an independent and multicenter cohort. Moreover, this score allowed reclassifying patients with discrepancies between the DSA presence and the histological diagnosis of antibody mediated rejection unlike kidney function. Thus, our refined SCR score could improve detection of SCR for closer and noninvasive monitoring, allowing early treatment of SCR lesions notably for patients DSA-positive and during lowering of immunosuppressive treatment.

KiT-GENIE, the French genetic biobank of kidney transplantation.

KiT-GENIE is a monocentric DNA biobank set up to consolidate the very rich and homogeneous DIVAT French cohort of kidney donors and recipients (D/R) in order to explore the molecular factors involved in kidney transplantation outcomes. We collected DNA samples for kidney transplantations performed in Nantes, and we leveraged GWAS genotyping data for securing high-quality genetic data with deep SNP and HLA annotations through imputations and for inferring D/R genetic ancestry. Overall, the biobank included 4217 individuals (n = 1945 D + 2,272 R, including 1969 D/R pairs), 7.4 M SNPs and over 200 clinical variables. KiT-GENIE represents an accurate snapshot of kidney transplantation clinical practice in Nantes between 2002 and 2018, with an enrichment in living kidney donors (17%) and recipients with focal segmental glomerulosclerosis (4%). Recipients were predominantly male (63%), of European ancestry (93%), with a mean age of 51yo and 86% experienced their first graft over the study period. D/R pairs were 93% from European ancestry, and 95% pairs exhibited at least one HLA allelic mismatch. The mean follow-up time was 6.7 years with a hindsight up to 25 years. Recipients experienced biopsy-proven rejection and graft loss for 16.6% and 21.3%, respectively. KiT-GENIE constitutes one of the largest kidney transplantation genetic cohorts worldwide to date. It includes homogeneous high-quality clinical and genetic data for donors and recipients, hence offering a unique opportunity to investigate immunogenetic and genetic factors, as well as donor-recipient interactions and mismatches involved in rejection, graft survival, primary disease recurrence and other comorbidities.

Very Low Dose Anti-Thymocyte Globulins Versus Basiliximab in Non-Immunized Kidney Transplant Recipients.

The choice between Basiliximab (BSX) or Anti-Thymocyte Globulin (ATG) as induction therapy in non-immunized kidney transplant recipients remains uncertain. Whilst ATG may allow steroid withdrawal and a decrease in tacrolimus, it also increases infectious complications. We investigated outcomes in non-immunized patients receiving a very low dosage of ATG versus BSX as induction. Study outcomes were patient/graft survival, cumulative probabilities of biopsy proven acute rejection (BPAR), infectious episode including CMV and post-transplant diabetes (PTD). Cox, logistic or linear statistical models were used depending on the studied outcome and models were weighted on propensity scores. 100 patients received ATG (mean total dose of 2.0 mg/kg) and 83 received BSX. Maintenance therapy was comparable. Patient and graft survival did not differ between groups, nor did infectious complications. There was a trend for a higher occurrence of a first BPAR in the BSX group (HR at 1.92; 95%CI: [0.77; 4.78]; p = 0.15) with a significantly higher BPAR episodes (17% vs 7.3%, p = 0.01). PTD occurrence was significantly higher in the BSX group (HR at 2.44; 95%CI: [1.09; 5.46]; p = 0.03). Induction with a very low dose of ATG in non-immunized recipients was safe and associated with a lower rate of BPAR and PTD without increasing infectious complications.

Primary Graft Function and 5 Year Insulin Independence After Pancreas and Islet Transplantation for Type 1 Diabetes: A Retrospective Parallel Cohort Study.

In islet transplantation (ITx), primary graft function (PGF) or beta cell function measured early after last infusion is closely associated with long term clinical outcomes. We investigated the association between PGF and 5 year insulin independence rate in ITx and pancreas transplantation (PTx) recipients. This retrospective multicenter study included type 1 diabetes patients who underwent ITx in Lille and PTx in Nantes from 2000 to 2022. PGF was assessed using the validated Beta2-score and compared to normoglycemic control subjects. Subsequently, the 5 year insulin independence rates, as predicted by a validated PGF-based model, were compared to the actual rates observed in ITx and PTx patients. The study enrolled 39 ITx (23 ITA, 16 IAK), 209 PTx recipients (23 PTA, 14 PAK, 172 SPK), and 56 normoglycemic controls. Mean[SD] PGF was lower after ITx (ITA 22.3[5.2], IAK 24.8[6.4], than after PTx (PTA 38.9[15.3], PAK 36.8[9.0], SPK 38.7[10.5]), and lower than mean beta-cell function measured in normoglycemic control: 36.6[4.3]. The insulin independence rates observed at 5 years after PTA and PAK aligned with PGF predictions, and was higher after SPK. Our results indicate a similar relation between PGF and 5 year insulin independence in ITx and solitary PTx, shedding new light on long-term transplantation outcomes.

Development and validation of multivariable prediction models of serological response to SARS-CoV-2 vaccination in kidney transplant recipients.

Repeated vaccination against SARS-CoV-2 increases serological response in kidney transplant recipients (KTR) with high interindividual variability. No decision support tool exists to predict SARS-CoV-2 vaccination response to third or fourth vaccination in KTR. We developed, internally and externally validated five different multivariable prediction models of serological response after the third and fourth vaccine dose against SARS-CoV-2 in previously seronegative, COVID-19-naïve KTR. Using 20 candidate predictor variables, we applied statistical and machine learning approaches including logistic regression (LR), least absolute shrinkage and selection operator (LASSO)-regularized LR, random forest, and gradient boosted regression trees. For development and internal validation, data from 590 vaccinations were used. External validation was performed in four independent, international validation cohorts comprising 191, 184, 254, and 323 vaccinations, respectively. LASSO-regularized LR performed on the whole development dataset yielded a 20- and 10-variable model, respectively. External validation showed AUC-ROC of 0.840, 0.741, 0.816, and 0.783 for the sparser 10-variable model, yielding an overall performance 0.812. A 10-variable LASSO-regularized LR model predicts vaccination response in KTR with good overall accuracy. Implemented as an online tool, it can guide decisions whether to modulate immunosuppressive therapy before additional active vaccination, or to perform passive immunization to improve protection against COVID-19 in previously seronegative, COVID-19-naïve KTR.

Antibody-mediated allograft rejection is associated with an increase in peripheral differentiated CD28-CD8+ T cells - Analyses of a cohort of 1032 kidney transplant recipients.

BACKGROUND: CD28-CD8+ T cells represent a differentiated CD8+ T cell subset that is found to be increased in various conditions associated with chronic antigenic stimulation such as aging, chronic viral infections, autoimmune diseases, cancers, and allotransplantation. METHODS: Using multivariate models, we analyzed a large cohort of 1032 kidney transplant patients in whom 1495 kidney graft biopsies were performed concomitant with a peripheral blood leukocyte phenotyping by flow cytometry. We investigated the association between the level of CD28-CD8+ T cells in the blood and the diagnosis of graft rejection according to the recent Banff classification of renal allograft pathology. FINDINGS: We found that antibody-mediated rejection (ABMR) was associated with a significant increase in the percentage as well as the absolute number of CD28-CD8+ T cells in the peripheral blood of kidney transplant patients at the time of biopsy. The confounder-adjusted mean difference of log percentage and log absolute value between the ABMR group and the normal/subnormal histology group were 0.29 (p=0.0004) and 0.38 (p=0.0004), respectively. Moreover, we showed that CD28-CD8+ T cells from the patients diagnosed with ABMR responded more rigorously to TCR and FcγRIIIA (CD16) engagement compared to their CD28+ counterparts as evidenced by an increase in the expression of IFNγ, TNFα, and CD107a. INTERPRETATION: Collectively, our data suggest that differentiated CD28-CD8+ T cells, with increased frequency, number, and function, may participate in the pathobiology of ABMR. Further studies are warranted to clarify the immunological role of this T cell subset in kidney graft rejection. FUNDING: Agence nationale de la recherche (France).

Impact of parathyroidectomy on kidney graft function in post-transplant tertiary hyperparathyroidism: a comparative study.

PURPOSE: Parathyroidectomy to treat tertiary hyperparathyroidism (THPT) is now on a par with calcimimetic treatment. The effects of cinacalcet and parathyroidectomy on kidney transplant function remain controversial. The aim of this study was to evaluate kidney transplant function in THPT patients treated either by parathyroidectomy, cinacalcet, or not treated. METHODS: Between 2009 and 2019, 231 patients with functional grafts presenting THPT, defined either by calcaemia superior to 2.5 mmol/L with elevated PTH level or hypercalcaemia with non-adapted PTH level 1 year after kidney transplantation, were included. Hyperparathyroid patients treated by cinacalcet and parathyroidectomy were matched for age, sex, graft rank, and baseline eGFR with cinacalcet-only and untreated patients. Conditional logistic regression models were used to compare eGFR variations 1 year after parathyroidectomy between operated patients and matched controls. Five-year survivals were compared with the Mantel-Cox test. RESULTS: Eleven patients treated with parathyroidectomy and cinacalcet were matched with 16 patients treated by cinacalcet-only and 29 untreated patients. Demographic characteristics were comparable between groups. Estimated odds ratios for eGFR evolution in operated patients compared with cinacalcet-only and untreated patients were 0.92 [95%CI 0.83-1.02] and 0.99 [0.89-1.10] respectively, indicating no significant impairment of eGFR 1 year after surgery. Five-year allograft survival was not significantly impaired in operated patients. CONCLUSIONS: Parathyroidectomy did not appear to substantially alter or improve graft function 1 year after surgery or 5-year allograft survival. It could be hypothesized that in addition to its known benefits, parathyroidectomy can be safely performed vis-à-vis graft function in tertiary hyperparathyroidism.

Incidence, Risk Factors and Outcomes of Kidney and Liver Cyst Infection in Kidney Transplant Recipient With ADPKD.

Introduction: Cyst infection is a known complication of autosomal dominant polycystic kidney disease (ADPKD). Here, we describe incidence, risk factors, clinical presentation, and outcomes of cyst infection in kidney transplant recipient. Methods: We conducted a single-center retrospective cohort study of patients with ADPKD with renal allografts between January 1, 2009, and October 31, 2020. Cyst infection diagnosis was based on previously described clinical and radiological criteria, using positron emission tomography when available. Results: A total of 296 patients with ADPKD with renal allografts were included, and 21 patients experienced 22 episodes of cyst infection over a median follow-up of 4 (2-7) years. The cumulative incidence rate was 3% at 1 year, 6 % at 5 years, and 12% at 10 years after transplantation. In multivariate analysis, history of cyst infection before transplantation was the only significant risk factor identified to predict the occurrence of cyst infection after kidney transplantation (hazard ratio [HR] 3.47, 95% CI 1.29-9.31). The clinical presentation at diagnosis of cyst infection included isolated fever in 5 (23%) episodes, acute kidney injury in 12 (55%), and severe sepsis/septic shock in 3 (14%) episodes. Among the 16 (73%) episodes with culture positivity, Escherichia coli was the most common pathogen. There was no difference between early (≤1 year after transplantation) and late (>1 year) cyst infection episodes in terms of clinical presentation and outcomes. Cyst infection was significantly associated with graft loss (HR 3.93, 95% CI 1.21-12.80), but no causal relationship could be established. Conclusion: Incidence of cyst infection in ADPKD after kidney transplantation is low, history of cyst infection representing the main risk factor.

Impact of Late and Recurrent Acute Graft Pyelonephritis on Long-Term Kidney Graft Outcomes.

Background: While Urinary tract infections are the most common infections in kidney transplant recipients, the impact of late acute graft pyelonephritis (AGPN) on graft outcomes remains unknown. Our study was performed to more precisely evaluate the long-term impact of AGPN. Methods: We included 9052 kidney and combined kidney-pancreas recipients who underwent transplantation between 2008 and 2018 from a French multicenter cohort. The relationships between AGPN and patient and graft survival were analyzed with a time-dependent multivariate Cox model. Results: The cumulative incidence of AGPN was 20.9%. A first episode of early AGPN is associated with a non-significant increase in the risk of graft failure (hazard ratio [HR], 1.27; 95% confidence interval [95% CI], 0.90 to 1.79). Though, cumulative number of AGPN episodes (HR = 1.51; 95% CI, 0.89 to 2.57 for two episodes and HR = 2.08; 95% CI, 1.17 to 3.69 for three or more episodes) is associated with an increased risk of graft failure. In contrast, when the first episode of AGPN occurred late (i.e., 6 months post transplantation), the risk of graft failure is significantly increased (HR = 2.25; 95% CI, 1.65 to 3.07), and this risk remains relatively stable with the recurrence of late AGPN episodes. The onset of late AGPN were also associated with a higher risk of patient death. Conclusion: This analysis shows that late AGPN and recurrent AGPN are both risk factors for a poor long-term graft outcome and mortality. Late AGPN should not be considered benign infections in post-transplantation follow-up.

Urinary metabolomic profiling from spontaneous tolerant kidney transplanted recipients shows enrichment in tryptophan-derived metabolites.

BACKGROUND: Operational tolerance is the holy grail in solid organ transplantation. Previous reports showed that the urinary compartment of operationally tolerant recipients harbor a specific and unique profile. We hypothesized that spontaneous tolerant kidney transplanted recipients (KTR) would have a specific urinary metabolomic profile associated to operational tolerance. METHODS: We performed metabolomic profiling on urine samples from healthy volunteers, stable KTR under standard and minimal immunosuppression and spontaneous tolerant KTR using liquid chromatography in tandem with mass spectrometry. Supervised and unsupervised multivariate computational analyses were used to highlight urinary metabolomic profile and metabolite identification thanks to workflow4metabolomic platform. FINDINGS: The urinary metabolome was composed of approximately 2700 metabolites. Raw unsupervised clustering allowed us to separate healthy volunteers and tolerant KTR from others. We confirmed by two methods a specific urinary metabolomic signature in tolerant KTR mainly driven by kynurenic acid independent of immunosuppressive drugs, serum creatinine and gender. INTERPRETATION: Kynurenic acid and tryptamine enrichment allowed the identification of putative pathways and metabolites associated with operational tolerance like IDO, GRP35 and AhR and indole alkaloids. FUNDING: This study was supported by the ANR, IRSRPL and CHU de Nantes.

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

Introduction: Decreased 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. Methods: Kidney 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. Results: From 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. Conclusion: The 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.

Kidney transplantation from expanded criteria donors: an increased risk of urinary complications - the UriNary Complications Of Renal Transplant (UNyCORT) study.

OBJECTIVES: To assess the impact of expanded criteria donors (ECD) on urinary complications in kidney transplantation. PATIENTS AND METHODS: The UriNary Complications Of Renal Transplant (UNyCORT) is a cohort study based on the French prospective Données Informatisées et VAlidées en Transplantation/Computerized and VAlidated Data in Transplantation (DIVAT) cohort. Data were extracted between 1 January 2002 and 1 January 2018 with 1-year minimum follow-up, in relation to 44 pre- and postoperative variables. ECD status was included according to United Network for Organ Sharing (UNOS) definition. The primary outcome of the UNyCORT study was the association between the donor's ECD/standard criteria donors (SCD) status and urinary complications at 1 year in uni- and multivariate analysis. Sub-group analysis, stratified analysis on ECD/SCD donor's status and transplant failure analysis were then conducted. RESULTS: Between 1 January 2002 and 1 January 2018, 10 279 kidney transplants in adult recipients were recorded within the DIVAT network. A total of 8559 (83.4%) donors were deceased donors and 1699 (16.6%) were living donors (LD). Among donation after circulatory death (DCD) donors, 224 (2.85%) were uncontrolled DCD and 93 (1.09%) were controlled DCD donors. A total of 3617 (43.9%) deceased donors were ECD. The overall urological complication rate was 16.26%. The donor's ECD status was significantly associated with an increased risk of urological complications at 1 year in multivariate analysis (odds ratio: 1.50, 95% CI 1.31-1.71; P < 0.001) and especially with stenosis and ureteric fistulae at 1 year. There is no association with LD, uncontrolled and controlled DCD. The placement of an endo-ureteric stent was beneficial in preventing urinary complications in all donors and particularly in ECD donors. CONCLUSION: The donor's ECD status is associated with a higher likelihood of stenosis and ureteric fistulae at 1 year. Recipients of grafts from ECD donors should probably be considered for closer urological monitoring and systematic preventive measures.

Time-dependent blood eosinophilia count increases the risk of kidney allograft rejection.

BACKGROUND: Growing evidence suggest that type 2 immune effectors play a role in solid organ transplantation. The aim of this study was to evaluate the impact of blood count eosinophils (BCEo) on immunological outcomes in kidney transplant recipients with stable graft function after 3 months post-transplant. METHOD: We performed cause-specific Cox model considering BCEo, the use of calcineurin inhibitors and systemic corticoids as time-dependent explicative variables on a prospective cohort of 1013 kidney transplant patients who experienced kidney allograft rejection and/or the appearance of de novo donor specific antibodies after excluding common causes of increased BCEo.. FINDINGS: BCEo ≥ 0.3 G/L was associated with a 3-fold increased risk of rejection independent of immunosuppressive regimen after 3 months post-transplant in patients without pre-transplant DSAs and with CNI-based immunosuppression. No association between BCEo either with donor specific antibodies or graft survival was noticed. INTERPRETATION: These observations in this large cohort support the hypothesis of eosinophils in allo-immunity in human and claim for further mechanistic research. FUNDING: This study was supported by the French National Research Agency, The "Institut de Recherche en Santé Respiratoire des Pays de la Loire" and the University hospital of Nantes.