Search

From parent populations (N = 50,000) stochastically generated, representing different levels of correlation (r) between the age at death and a hypothetical biological indicator (r = 0.8-0.98), reference samples and target demographic samples are randomly drawn. Two iterative techniques, proportional fitting procedure and Bayesian, are used to estimate from the reference samples the age distribution of the targets. Due to the random fluctuations of the pattern of aging, both in the reference and target samples, these techniques converge only in expectation toward the true value of a distribution, but not in practice for any particular realization. Nevertheless, these techniques allow the estimation of the average of an age distribution, even if its shape is unknown. Under the hypothesis that the target sample is drawn from a stationary population, this average represents the life expectancy at 20 years (plus 20 years). Using this mean age at death for the adults and the juvenility index at death (D5-14/D20-[Omega]), a new set of paleodemo-graphic estimators were derived from 40 archaic life tables. For a hypothesized stable population, they give the life expectancy at birth and at 20 years, and the probability of death at 1 and 5 years. KEY WORDS Iterative proportional fitting, Age distribution, Demographic estimators

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., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: The clinical standard for pancreas preservation for transplantation is static cold storage (SCS). Oxygenation during preservation has been shown to be advantageous in clinical studies. This study evaluates the efficiency of different oxygenation modalities during hypothermic pancreas preservation., Methods: Thirty-two porcine pancreases were procured in a controlled donation after circulatory death model and were divided to be preserved in 8 groups: (1) SCS, (2) hypothermic machine perfusion (HMP), (3) hypothermic oxygenated machine perfusion (HOPE) with 21% oxygen, (4) HOPE and 100%, (5) SCS and oxygen carrier, M101, (6) HMP and M101, (7) HOPE 21% and M101, and (8) HOPE 100% and M101. All the groups underwent 24 h of hypothermic preservation, followed by 2 h of normothermic reperfusion. Oxygen partial pressures were assessed using parenchymal probes. Perfusion parameters, perfusate samples, and tissue biopsies were analyzed., Results: This study showed that HMP was linked to higher tissue oxygen partial pressures, lower succinate levels, and better reperfusion parameters. Furthermore, the addition of M101 to either SCS or HMP was associated with lower succinate and creatinine phosphokinase accumulation, suggesting a protective effect against ischemia., Conclusions: Our research has demonstrated the efficacy of machine perfusion in hypothermic conditions in providing oxygen to the pancreas during preservation and conditioning the pancreatic microvasculature for reperfusion during transplantation. Furthermore, the addition of M101 suggests a protective effect on the graft from ischemia., Competing Interests: B.M. and J.B. received grant funding and technical support from Institut Georges Lopez and Hémarina. L.B. provided expertise for Astellas and Bristol Myers Squibb. The other authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The observation decades ago that inflammatory injuries because of an alloimmune response might be present even in the absence of concomitant clinical impairment in allograft function conduced to the later definition of subclinical rejection. Many studies have investigated the different subclinical rejections defined according to the Banff classification (subclinical T cell-mediated rejection and antibody-mediated rejection), overall concluding that these episodes worsened long-term allograft function and survival. These observations led several transplant teams to perform systematic protocolar biopsies to anticipate treatment of rejection episodes and possibly prevent allograft loss. Paradoxically, the invasive characteristics and associated logistics of such procedures paved the way to investigate noninvasive biomarkers (urine and blood) of subclinical rejection. Among them, several research teams proposed a blood gene signature developed from cohort studies, most of which achieved excellent predictive values for the occurrence of subclinical rejection, mainly antibody-mediated rejection. Interestingly, although all identified genes relate to immune subsets and pathways involved in rejection pathophysiology, very few transcripts are shared among these sets of genes, highlighting the heterogenicity of such episodes and the difficult but mandatory need for external validation of such tools. Beyond this, their application and value in clinical practice remain to be definitively demonstrated in both biopsy avoidance and prevention of clinical rejection episodes. Their combination with other biomarkers, either epidemiological or biological, could contribute to a more accurate picture of a patient's risk of rejection and guide clinicians in the follow-up of kidney transplant recipients., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Preeclampsia is a pregnancy-specific condition characterized by gestational hypertension associated with proteinuria or organ dysfunction after 20 weeks of gestation. It complicates 2 to 8 % of pregnancies worldwide and represents the leading cause of maternal and fetal mortality in developed countries. The only definitive treatment remains termination of pregnancy and delivery of the placenta. Prompt assessment of maternal and fetal status should be held in search of severity criteria and adequate management of this condition according to gestational age. Foremost concerns for pregnant patients are impending eclampsia or placental abruption, while fetal complications arise from placental insufficiency and risks associated with premature pregnancy termination. The sole efficient prophylaxis of preeclampsia in current state of evidence is aspirin at a dosage of 160 mg per day in high risk patients. Preeclampsia is now recognized as a high-risk factor for cardiovascular, renal, and neurological diseases and should therefore be considered as an opportunity for screening and prevention.

Background: About 10-20% of pancreas allografts are still lost in the early postoperative period despite the identification of numerous detrimental risk factors that correlate with graft thrombosis., Methods: We conducted a multicenter study including 899 pancreas transplant recipients between 2000 and 2018. Early pancreas failure due to complete thrombosis, long-term pancreas, kidney and patient survivals were analyzed and adjusted to donor, recipient and perioperative variables using a multivariate cause-specific Cox model stratified to transplant centers., Results: Pancreas from donors with history of hypertension (6.7%), as well as with high body mass index (BMI), were independently associated with an increased risk of pancreas failure within the first 30 post-operative days (respectively, HR= 2.57, 95% CI from 1.35 to 4.89 and HR= 1.11, 95% CI from 1.04 to 1.19). Interaction term between hypertension and BMI was negative. Donor hypertension also impacted long-term pancreas survival (HR= 1.88, 95% CI from 1.13 to 3.12). However, when pancreas survival was calculated after the postoperative day 30, donor hypertension was no longer a significant risk factor (HR= 1.22, 95% CI from 0.47 to 3.15). A lower pancreas survival was observed in patients receiving a pancreas from a hypertensive donor without RAAS (Renin Angiotensin Aldosterone System) blockers compared to others (50% vs 14%, p < 0.001). Pancreas survival was similar among non-hypertensive donors and hypertensive ones under RAAS blockers., Conclusion: Donor hypertension was a significant and independent risk factor of pancreas failure. The well-known pathogenic role of renin-angiotensin-aldosterone system seems to be involved in the genesis of this immediate graft failure., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Masset, Branchereau, Buron, Karam, Rabeyrin, Renaudin, Le Borgne, Badet, Matillon, Legendre, Glotz, Antoine, Giral, Dantal, Cantarovich and DIVAT Consortium.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chetboun, Masset, Maanaoui, Defrance, Gmyr, Raverdy, Hubert, Bonner, Supiot, Kerleau, Blancho, Branchereau, Karam, Chelghaf, Houzet, Giral, Garandeau, Dantal, Le Mapihan, Jannin, Hazzan, Caiazzo, Kerr-Conte, Vantyghem, Cantarovich and Pattou.)

Competing Interests: The authors declare no conflicts of interest.

The pancreas is very susceptible to ischemia-reperfusion injury. Early graft losses due to pancreatitis and thrombosis represent a major issue after pancreas transplantation. Sterile inflammation during organ procurement (during brain death and ischemia-reperfusion) and after transplantation affects organ outcomes. Sterile inflammation of the pancreas linked to ischemia-reperfusion injury involves the activation of innate immune cell subsets such as macrophages and neutrophils, following tissue damage and release of damage-associated molecular patterns and pro-inflammatory cytokines. Macrophages and neutrophils favor tissue invasion by other immune cells, have deleterious effects or functions, and promote tissue fibrosis. However, some innate cell subsets may promote tissue repair. This outburst of sterile inflammation promotes adaptive immunity activation via antigen exposure and activation of antigen-presenting cells. Better controlling sterile inflammation during pancreas preservation and after transplantation is of utmost interest in order to decrease early allograft loss (in particular thrombosis) and increase long-term allograft survival. In this regard, perfusion techniques that are currently being implemented represent a promising tool to decrease global inflammation and modulate the immune response.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Masset, Kerleau, Blancho, Hourmant, Walencik, Ville, Kervella, Cantarovich, Houzet, Giral, Garandeau, Dantal and the Nantes DIVAT Consortium.)

Background and Aims: In hemodialysis patients, monitoring 25-hydroxyvitamin D (25(OH)D) levels is recommended. It is however unclear if monitoring 1,25-dihydroxyvitamin D (1,25(OH) 2 D) levels is interesting., Materials and Methods: We repeatedly measured 1,25(OH) 2 D (DiaSorin Liaison analyser) and 25(OH)D (LCMS/MS) concentrations in patients newly treated by active or native vitamin D to study the impact of such treatments on serum concentrations., Results: Ten patients were included in the native and 12 in the active vitamin D group. In the native group, a significant increase was observed between the baseline and the last 25(OH)D concentrations available (21.65[17.39;25.26] versus 33.49[28.60;40.30] ng/mL, p = 0.0059). The baseline and last available 1,25(OH) 2 D concentrations were not different (12.15[4.25;15.40] versus 11.35[9.72;21.85] pg/mL, p = 0.5566). In the active group, no difference was observed between the baseline and the last 25(OH)D concentrations (51.70[42.97;63.95] versus 50.89[42.02;64.49] ng/mL, p = 0.5186). The same observation was made for 1,25 (OH) 2 D concentrations (25.65[17.05;41.85] versus 28.70[23.36;43.73] pg/mL, p = 0.6221). Using a linear mixed model, a significant change over time was only observed in 25(OH)D serum levels for patients treated by with native vitamin D., Conclusion: Measuring 1,25(OH)2D levels in patients newly treated by active vitamin D does not seem useful in monitoring active vitamin D therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The mechanisms regulating CD8 + T cell migration to nonlymphoid tissue during inflammation have not been fully elucidated, and the migratory properties of effector memory CD8 + T cells that re-express CD45RA (TEMRA CD8 + T cells) remain unclear, despite their roles in autoimmune diseases and allotransplant rejection., Methods: We used single-cell proteomic profiling and functional testing of CD8 + T cell subsets to characterize their effector functions and migratory properties in healthy volunteers and kidney transplant recipients with stable or humoral rejection., Results: We showed that humoral rejection of a kidney allograft is associated with an accumulation of cytolytic TEMRA CD8 + T cells in blood and kidney graft biopsies. TEMRA CD8 + T cells from kidney transplant recipients exhibited enhanced migratory properties compared with effector memory (EM) CD8 + T cells, with enhanced adhesion to activated endothelium and transmigration in response to the chemokine CXCL12. CXCL12 directly triggers a purinergic P2×4 receptor-dependent proinflammatory response of TEMRA CD8 + T cells from transplant recipients. The stimulation with IL-15 promotes the CXCL12-induced migration of TEMRA and EM CD8 + T cells and promotes the generation of functional PSGL1, which interacts with the cell adhesion molecule P-selectin and adhesion of these cells to activated endothelium. Although disruption of the interaction between functional PSGL1 and P-selectin prevents the adhesion and transmigration of both TEMRA and EM CD8 + T cells, targeting VLA-4 or LFA-1 (integrins involved in T cell migration) specifically inhibited the migration of TEMRA CD8 + T cells from kidney transplant recipients., Conclusions: Our findings highlight the active role of TEMRA CD8 + T cells in humoral transplant rejection and suggest that kidney transplant recipients may benefit from therapeutics targeting these cells., (Copyright © 2022 by the American Society of Nephrology.)

While most viral infections cause mild symptoms and a spontaneous favorable resolution, some can lead to severe or protracted manifestations, specifically in immunocompromised hosts. Kidney injuries related to viral infections may have multiple causes related to the infection severity, drug toxicity or direct or indirect viral-associated nephropathy. We review here the described virus-associated nephropathies in order to guide diagnosis strategies and treatments in cases of acute kidney injury (AKI) occurring concomitantly with a viral infection. The occurrence of virus-associated nephropathy depends on multiple factors: the local epidemiology of the virus, its ability to infect renal cells and the patient's underlying immune response, which varies with the state of immunosuppression. Clear comprehension of pathophysiological mechanisms associated with a summary of described direct and indirect injuries should help physicians to diagnose and treat viral associated nephropathies.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Osmanodja, Stegbauer, Kantauskaite, Rump, Heinzel, Reindl-Schwaighofer, Oberbauer, Benotmane, Caillard, Masset, Kerleau, Blancho, Budde, Grunow, Mikhailov, Schrezenmeier and Ronicke.)

Introduction: In kidney transplant recipients, belatacept is usually pursued indefinitely after it has been started. In the setting of the belatacept shortage and after having evaluated the benefit-risk ratio, we established a strategy consisting of time-limited belatacept therapy/transient calcineurin inhibitor withdrawal, whose results are analyzed in that study., Methods: We considered all the kidney transplant recipients that had been switched from conventional immunosuppressive therapy to belatacept and then for whom belatacept has been withdrawn intentionally. Furthermore, in the first 8 patients, we assessed changes in peripheral blood mononuclear cells (PBMC) transcriptome using RNAseq before and 3 months after belatacept withdrawal., Results: Over the study period, 28 out of 94 patients had belatacept intentionally withdrawn including 25 (89%) switched to low-dose CNI. One rejection due to poor compliance occurred. The eGFR after 12 months remained stable from 48 ± 19 mL.1.73 m -2 to 46 ± 17 mL.1.73 m -2 ( p = 0.68). However, patients that resumed belatacept/withdrew CNIs ( n = 10) had a trend towards a better eGFR comparing with the others ( n = 15): 54 ± 20 mL.1.73 m -2 vs. eGFR 43 ± 16 mL.1.73 m -2 , respectively ( p = 0.15). The only factor associated with belatacept resumption was when the withdrawal took place during the COVID-19 outbreak. Transcriptome analysis of PBMCs, did not support rebound in alloimmune response., Conclusions: These findings underpin the use of belatacept as part of a time-limited therapy, in selected kidney transplant recipients, possibly as an approach to allow efficient vaccination against SARS-CoV-2.

Introduction: Kidney transplant recipients (KTRs) are prone to develop severe COVID-19 and are less well protected by vaccine than immunocompetent subjects. Thus, the use of neutralizing anti-SARS-CoV-2 monoclonal antibody (MoAb) to confer a passive immunity appears attractive in KTRs., Methods: We performed a French nationwide study to compare COVID-19-related hospitalization, 30-day admission to intensive care unit (ICU), and 30-day death between KTRs who received an early infusion of MoAb (MoAb group) and KTRs who did not (control group). Controls were identified from the COVID-SFT registry (NCT04360707) using a propensity score matching with the following covariates: age, sex, delay between transplantation and infection, induction and maintenance immunosuppressive therapy, initial symptoms, and comorbidities., Results: A total of 80 KTRs received MoAb between February 2021 and June 2021. They were matched to 155 controls. COVID-19-related hospitalization, 30-day admission to ICU, and 30-day death were less frequently observed in the MoAb group (35.0% vs. 49.7%, P  = 0.032; 2.5% vs. 15.5%, P  = 0.002; 1.25% vs. 11.6%, P  = 0.005, respectively). No patient required mechanical ventilation in the MoAb group. The number of patients to treat to prevent 1 death was 9.7., Conclusion: The early use of MoAb in KTRs with a mild form of COVID-19 largely improved outcomes in KTRs., (© 2022 International Society of Nephrology. Published by Elsevier Inc.)

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., (© 2022 International Society of Nephrology. Published by Elsevier Inc.)

Higher education in evolutionary anthropology involves providing students with in-depth knowledge of biological and cultural heritage sites and collections that are frequently inaccessible. Indeed, most sites, fossils, and archaeological remains can be visited or manipulated only rarely and solely by specialists with extensive experience. Owing to the development of 3D and medical imaging techniques, this fragile heritage is now more widely accessible, and in a dynamic way. However, exclusive adoption of virtual teaching and learning has a negative impact on student engagement and, naturally, on exchanges with instructors, and thus cannot be used without some reservations. In the ITAP ( Immersion dans les Terrains de l'Anthropologie biologique et de la Préhistoire ) project of the higher education STEP ( Soutien à la Transformation et à l'Expérimentation Pédagogiques ) transformation program at the University of Bordeaux, we combine student-active teaching with Master's students fully immersed in ongoing fieldwork, laboratory study, and dissemination of research results in order to develop more individually shaped learning curricula and to foster both professional and new interdisciplinary skills. Here, we present examples of experiments conducted in the ITAP project using both authentic and virtual collections of archaeological, experimental, and reference materials that help to break down the barriers between research activities and higher education, as well as providing a more general appraisal of the appropriate use of virtual tools in higher education by combining them with real-life situations., Competing Interests: The authors declare no potential conflict of interest., (© 2022 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Since the beginning of our pancreas transplant programme, plasma C-peptide was routinely measured daily during the postoperative period. We aimed to evaluate the clinical interest of the C-peptide in the follow-up of pancreas transplantation with a particular look on early graft failure. From 2000 to 2016, 384 pancreas transplantations were evaluated. We collected and compared C-peptide, glycaemia and adjusted C-peptide (aCP; calculated based on C-peptide, glycaemia and creatininaemia) in patients with and without pancreas failure within 30 days after surgery. Variations of glycaemia, C-peptide and aCP between the day before and the day of failure were also recorded. The difference of aCP was significant during the first week after transplantation between patients with thrombosis and those with functional allograft: 63.2 vs. 26.7 on day 1, P = 0.0003; 61.4 vs. 26.7 on day 3, P < 0.0001; 64.8 vs. 5.7 on day 7, P < 0.0001, respectively. Glycaemia had a median increase of 8% on the day of failure, whereas C-peptide and aCP had, respectively, a median decrease of 88% and 83%. C-peptide monitoring after pancreas transplantation may help to identify graft function and early failure. This sensitive biomarker could allow pre-emptive diagnosis of an early thrombotic event allowing the possibility of rescue interventions., (© 2021 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

There are no studies which have compared the risk of severe COVID-19 and related mortality between transplant recipients and nontransplant patients. We enrolled two groups of patients hospitalized for COVID-19, that is, kidney transplant recipients (KTR) from the French Registry of Solid Organ Transplant (n = 306) and a single-center cohort of nontransplant patients (n = 795). An analysis was performed among subgroups matched for age and risk factors for severe COVID-19 or mortality. Severe COVID-19 was defined as admission (or transfer) to an intensive care unit, need for mechanical ventilation, or death. Transplant recipients were younger and had more comorbidities compared to nontransplant patients. They presented with higher creatinine levels and developed more episodes of acute kidney injury. After matching, the 30-day cumulative incidence of severe COVID-19 did not differ between KTR and nontransplant patients; however, 30-day COVID-19-related mortality was significantly higher in KTR (17.9% vs 11.4%, respectively, p = .038). Age >60 years, cardiovascular disease, dyspnea, fever, lymphopenia, and C-reactive protein (CRP) were associated with severe COVID-19 in univariate analysis, whereas transplant status and serum creatinine levels were not. Age >60 years, hypertension, cardiovascular disease, diabetes, CRP >60 mg/L, lymphopenia, kidney transplant status (HR = 1.55), and creatinine level >115 µmol/L (HR = 2.32) were associated with COVID-19-related mortality in univariate analysis. In multivariable analysis, cardiovascular disease, dyspnea, and fever were associated with severe disease, whereas age >60 years, cardiovascular disease, dyspnea, fever, and creatinine level>115 µmol/L retained their independent associations with mortality. KTR had a higher COVID-19-related mortality compared to nontransplant hospitalized patients., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Kidney transplant recipients have been supposed vulnerable to severe Covid-19 infection, due to their comorbidities and immunosuppressive therapies. Mild-term complications of Covid-19 are currently unknown, especially in this population. Herein, we report two cases of BKV replication after non-severe SARS-CoV-2 infection. The first case was a 59-year-old man, transplanted 3 months ago, with recent history of slight BKV viremia (3.3 log 10 DNA copies/ml). Despite strong reduction of maintenance immunosuppression (interruption of mycophenolic acid and important decrease of calcineurin inhibitors), BKV replication largely increased after Covid-19 and viremia persisted at 4.5 log copy/ml few months later. The second case was a 53-year-old woman, transplanted 15 years ago. She had a recent history of BKV cystitis, which resolved with a decrease of MPA dosage. Few weeks after SARS-CoV-2 infection, she presented recurrence of lower urinary tract symptoms. Our reports highlight that SARS-CoV-2 infection, even without severity, could disrupt immune system and particularly lymphocytes, thus leading to viral replication. Monitoring of viral replications after Covid-19 in kidney transplant recipients could permit to confirm these preliminary observations., (© 2020 Wiley Periodicals LLC.)

Notwithstanding the ongoing coronavirus disease-2019 (Covid-19) pandemic, information on its clinical presentation and prognosis in recipients of a kidney transplant remain scanty. The aim of this registry-based observational study was to explore characteristics and clinical outcomes of recipients of kidney transplants included in the French nationwide Registry of Solid Organ Transplant Recipients with Covid-19. Covid-19 was diagnosed in symptomatic patients who had a positive PCR assay for SARS-CoV-2 or having typical lung lesions on imaging. Clinical and laboratory characteristics, management of immunosuppression, treatment for Covid-19, and clinical outcomes (hospitalization, admission to intensive care unit, mechanical ventilation, or death) were recorded. Risk factors for severe disease or death were determined. Of the 279 patients, 243 were admitted to hospital and 36 were managed at home. The median age of hospitalized patients was 61.6 years; most had comorbidities (hypertension, 90.1%; overweight, 63.8%; diabetes, 41.3%; cardiovascular disease, 36.2%). Fever, cough, dyspnea, and diarrhea were the most common symptoms on admission. Laboratory findings revealed mild inflammation frequently accompanied by lymphopenia. Immunosuppressive drugs were generally withdrawn (calcineurin inhibitors: 28.7%; antimetabolites: 70.8%). Treatment was mainly based on hydroxychloroquine (24.7%), antiviral drugs (7.8%), and tocilizumab (5.3%). Severe Covid-19 occurred in 106 patients (46%). Forty-three hospitalized patients died (30-day mortality 22.8%). Multivariable analysis identified overweight, fever, and dyspnea as independent risk factors for severe disease, whereas age over 60 years, cardiovascular disease, and dyspnea were independently associated with mortality. Thus, Covid-19 in recipients of kidney transplants portends a high mortality rate. Proper management of immunosuppression and tailored treatment of this population remain challenging., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)