A Universal Bleeding Risk Score in Native and Allograft Kidney Biopsies: A French Nationwide Cohort Study

BackgroundThe risk of bleeding after percutaneous biopsy in kidney transplant recipients is usually low but may vary. A pre-procedure bleeding risk score in this population is lacking.MethodsWe assessed the major bleeding rate (transfusion, angiographic intervention, nephrectomy, hemorrhage/hematoma) at 8 days in 28,034 kidney transplant recipients with a kidney biopsy during the 2010-2019 period in France and compared them to 55,026 patients with a native kidney biopsy as controls.ResultsThe rate of major bleeding was low (angiographic intervention: 0.2%, hemorrhage/hematoma: 0.4%, nephrectomy: 0.02%, blood transfusion: 4.0%). A new bleeding risk score was developed (anemia = 1, female gender = 1, heart failure = 1, acute kidney failure = 2 points). The rate of bleeding varied: 1.6%, 2.9%, 3.7%, 6.0%, 8.0%, and 9.2% for scores 0 to 5, respectively, in kidney transplant recipients. The ROC AUC was 0.649 (0.634-0.664) in kidney transplant recipients and 0.755 (0.746-0.763) in patients who had a native kidney biopsy (rate of bleeding: from 1.2% for score = 0 to 19.2% for score = 5).ConclusionsThe risk of major bleeding is low in most patients but indeed variable. A new universal risk score can be helpful to guide the decision concerning kidney biopsy and the choice of inpatient vs. outpatient procedure both in native and allograft kidney recipients

Model Inference and Security Testing in the SPaCIoS Project

International audienceThe SPaCIoS project has as goal the validation and testing of security properties of services and web applications. It proposes a methodology and tool collection centered around models described in a dedicated specification language, supporting model inference, mutation-based testing, and model checking. The project has developed two approaches to reverse engineer models from implementations. One is based on remote interaction (typically through an HTTP connection) to observe the runtime behaviour and infer a model in black-box mode. The other is based on analysis of application code when available. This paper presents the reverse engineering parts of the project, along with an illustration of how vulnerabilities can be found with various SPaCIoS tool components on a typical security benchmark

Influence of Fc gamma rIIIA genetic polymorphism on lymphocyte depletion in kidney transplanted patients

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Deficits in Information Transfer between Hospital-Based and Primary-Care Physicians, the Case of Kidney Disease: A Cross-Sectional Study

International audienceBACKGROUND: Late recognition plays an important role in prognosis associated with kidney disease; thus, information transfer at hospital discharge regarding kidney disease is crucial. Whether it is notified in patients' hospital discharge summary (HDS) is presently largely unknown. STUDY DESIGN: Cross-sectional. SETTING AND PARTICIPANTS: The prevalence of kidney dysfunction [estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2)] and its reporting to primary-care physicians from 26 units [11 surgery, 11 medical, 4 intensive care units (ICUs)] of a university hospital were analyzed in 14,000 hospitalizations. PREDICTOR: eGFR. OUTCOME: Notification of kidney dysfunction in HDS. MEASUREMENTS: GFR was estimated from serum creatinine using the Modification of Diet in Renal Disease formula. RESULTS: Kidney dysfunction was frequent (27.2 %) but infrequently notified in the main-body of the HDS (overall 25.3 %, medical 25 %, surgical 16.3 %, ICU 48.4 %) even when severe (eGFR 15-29.9 ml/min/1.73 m(2) was notified in 68.8, 38.5, and 79.8 % of HDSs in medical, surgical and ICUs, respectively). Notification in the HDS conclusion was rare (overall 11.4 %, medical 9.8 %, surgical 8.4 %, ICU 27.5 %). Reporting remained low when eGFR remained abnormal at discharge (medical 35.8 %, surgical 22.5 %, ICU 62.2 %) but was worse for acute kidney injury (16.0, 17.1, and 37.7 %, respectively). The optimal eGFR cut-off for reporting was 39 ml/min/1.73 m(2). Longer durations of hospitalization, greater numbers of creatinine measurements and of abnormal eGFR were associated with notification, regardless of the type of unit. LIMITATIONS: Lack of data to define acute or chronic kidney injury with precision. CONCLUSIONS: Kidney dysfunction is frequent in hospitalized patients but is usually not notified, even when severe or still present at discharge, suggesting that it is not considered important to disclose to primary-care physicians. This lack of information may decrease physicians' awareness, and may affect continuity of care in patients with kidney dysfunction

Diffuse panbronchiolitis and IgA nephropathy

Chronic infections of respiratory tracts are suspected to promote the development of IgA nephropathy. From the study of one case, we discuss the hypothesis that infections by pseudomonas aeruginosa might promote an increased bronchial production of IgA1, which could pass in the serum and settle into immune complexes in the kidney. A 67 years old woman presented simultaneously IgA nephropathy and diffuse panbronchiolitis. The evolution was marked by repeated infections by pseudomonas aeruginosa. The study of lung biopsy by immunohistochemistry showed intense expression of IgA1 in bronchioles, increased when compared to large bronchi. In contrast, expression of the transport receptor (pIgR) was decreased in inflamed bronchioles and preserved in bronchi. The BAL during an infection by pseudomonas aeruginosa showed increased secretory (S-) IgA with predominance of S-IgA1 (28.6 µg/mL versus S-IgA2 8.4µg/mL). In the sera collected during two infectious episodes and compared with an inter-critical sample, we found an increased IgA1 (776 and 549µg/mL versus 455µg/mL), associated with increased polymeric IgA (estimated at 40-50%, versus normally 10%). The increased expression of IgA1 in bronchiolar tissue, BAL and serum in the case of our patient further suggests a putative link between IgA nephropathy and diffuse panbronchiolitis, through exuberant production of IgA1 induced by pseudomonas aeruginosa infections

An adjustable predictive score of graft survival in kidney transplant patients and the levels of risk linked to de novo donor-specific anti-HLA antibodies.

International audienceMost predictive models and scores of graft survival in renal transplantation include factors known before transplant or at the end of the first year. They cannot be updated thereafter, even in patients developing donor-specific anti-HLA antibodies and acute rejection.We developed a conditional and adjustable score for prediction of graft failure (AdGFS) up to 10 years post-transplantation in 664 kidney transplant patients. AdGFS was externally validated and calibrated in 896 kidney transplant patients.The final model included five baseline factors (pretransplant non donor-specific anti-HLA antibodies, donor age, serum creatinine measured at 1 year, longitudinal serum creatinine clusters during the first year, proteinuria measured at 1 year), and two predictors updated over time (de novo donor-specific anti-HLA antibodies and first acute rejection). AdGFS was able to stratify patients into four risk-groups, at different post-transplantation times. It showed good discrimination (time-dependent ROC curve at ten years: 0.83 (CI95% 0.76-0.89)

Impaired autophagy increases susceptibility to endotoxin-induced chronic pancreatitis

International audienceChronic pancreatitis (CP) is associated with elevated plasma levels of bacterial lipopolysaccharide (LPS) and we have demonstrated reduced acinar cell autophagy in human CP tissue. Therefore, we investigated the role of autophagy in experimental endotoxin-induced pancreatic injury and aimed to identify LPS in human CP tissue. Pancreatic Atg7-deficient mice were injected with a single sub-lethal dose of LPS. Expression of autophagy, apoptosis, necroptosis, and inflammatory markers was determined 3 and 24 h later utilizing immunoblotting and immunofluorescence. The presence of LPS in pancreatic tissue from mice and from patients and healthy controls was determined using immunohistochemistry, immunoblots, and chromogenic assay. Mice lacking pancreatic autophagy exhibited local signs of inflammation and were particularly sensitive to the toxic effect of LPS injection as compared to control mice. In response to LPS, Atg7Δpan mice exhibited enhanced vacuolization of pancreatic acinar cells, increase in TLR4 expression coupled to enhanced expression of NF-κΒ, JNK, and pro-inflammatory cytokines by acinar cells and enhanced infiltration by myeloid cells (but not Atg7F/F controls). Cell death was enhanced in Atg7Δpan pancreata, but only necroptosis and trypsin activation was further amplified following LPS injection along with elevated pancreatic LPS. The presence of LPS was identified in the pancreata from all 14 CP patients examined but was absent in the pancreata from all 10 normal controls. Altogether, these results support a potential role for metabolic endotoxemia in the pathogenesis of CP. Moreover, the evidence also supports the notion that autophagy plays a major cytoprotective and anti-inflammatory role in the pancreas, and blunting metabolic endotoxemia-induced CP

Persistant Lymphopenia after Thymoglobulin (R) in Kidney Transplantation Is Associated with Clinical and Genetic Factors

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