Anomalies de la voie alterne du complément au cours du HELLP syndrome

Introduction : Le HELLP (Hemolysis, Elevated Liver enzymes and Low Platelets) syndrome, syndrome frontière entre prééclampsie et microangiopathie thrombotique (MAT), est une pathologie rare mais redoutée de la grossesse exposant à des complications materno-fœtales, parmi lesquelles l'insuffisance rénale aigue. Sa physiopathologie reste à ce jour incomplètement élucidée et le rôle de la voie alterne du complément, pourvoyeur de lésions de MAT, reste à définir. Méthodes et résultats : L'étude, multicentrique et prospective, a permis l'exploration de la voie alterne du complément et de son système de régulation chez 45 patientes atteintes de HELLP syndrome. Quarante pour cent d'anomalies immunochimiques ou génétiques ont été documentées. Onze pour cent de mutations et 8,8% de polymorphismes rares des gènes codant pour les protéines de régulation de la voie alterne du complément (FH- FI- MCP) ont été retrouvées, sans corrélation significative avec la survenue de complications néphrologiques. Conclusion : Le HELLP syndrome est relié à des anomalies génétiques de la voie alterne du complément qui, bien qu'elles ne représentent pas le facteur génétique déterminant, suggère son appartenance au spectre des microangiopathies thrombotiques de la grossesse. La dysrégulation du système du complément dans le HELLP syndrome, démasque une nouvelle facette de la complexité de ses mécanismes physiopathologiques et suggère une nouvelle cible thérapeutique potentielle.NANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF

Obstetric Nephrology: AKI and Thrombotic Microangiopathies in Pregnancy

International audienceAKI in pregnancy remains a cause of significant fetomaternal mortality and morbidity, particularly in developing countries. Hypertensive complications of pregnancy (preeclampsia/eclampsia or hemolysis, elevated liver enzymes, and low platelets count syndrome) are the leading cause of AKI in pregnancy worldwide. Thrombotic microangiopathy is another peculiar and devastating cause of AKI in pregnancy. During the last decade, our understanding, and in some cases, our management, of these causes of AKI in pregnancy has dramatically improved. For instance, convincing data have linked pre-eclampsia/eclampsia to an increase in circulating antian-giogenic factors soluble Flt 1 and endoglin, which induce endothelial cell dysfunction, hypertension, and proteinuria. Several distinct pathogenic mechanisms underlying thrombotic microangiopathy, including throm-botic microangiopathy occurring during pregnancy, have been established. Thrombotic microangiopathy, which can present as hemolytic uremic syndrome or thrombotic thrombocytopenic purpura, can be reclassified in four potentially overlapping subtypes: disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 deficiency-related thrombotic microangiopathy, complement alternative pathway dysregulation-related thrombotic microangiopathy, secondary thrombotic microangiopathy (verotoxin and antiangiogenic drugs), and thrombotic microangiopathy of undetermined mechanism. In most cases, pregnancy is only a precipitating factor for thrombotic microangiopathy. Treatment of thrombotic microangiopathy occurring during pregnancy should be tailored to the underlying pathogenic mechanism: (1) restoration of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 serum activity in the setting of thrombotic thrombocytopenic purpura through plasma exchanges and in some cases, B cell-depleting therapy and (2) inhibition of complement alternative pathway activation in atypical hemolytic uremic syndrome using antiC5 blocking antibody (eculizumab)

Eosinophilia Due to Central Venous Catheter in Hemodialysis Patients

International audienceNo abstract availabl

Unique and specific Agrobacterium diversity in urinary microbiota of tolerant kidney transplanted recipients

International audienceHost‐microbiota interactions can modulate the immune system both at local and systemic levels, with potential consequences for organ transplantation outcomes. In this study, we hypothesized that differences in the urinary microbiome following kidney transplantation would be associated with posttransplantation status: stable, minimally immunosuppressed, or tolerant. One hundred thirteen urine samples from stable (n = 51), minimally immunosuppressed (n = 19), and spontaneously tolerant (n = 16) patients, paired with age‐matched controls (n = 27) were profiled and compared to each other at a taxonomic level with special interest in the immunosuppressive regimen. All comparisons and correlations were adjusted on sex and time posttransplantation. Our results highlighted a unique and specific urinary microbiota associated with spontaneous tolerance characterized by a high diversity and a clear Proteobacteria profile. Finally, we report that this profile is (1) impacted by gender, (2) inversely correlated with immunosuppressive drugs (calcineurin inhibitors and mammalian target of rapamycin inhibitors), and (3) stable in time

Comparison of machine perfusion versus cold storage in kidney transplant recipients from expanded criteria donors: a cohort-based study

International audienceBackground Most studies comparing the efficacy of hypothermic machine perfusion (HMP) versus static cold storage (SCS) are based on short-term outcomes. We aimed to better evaluate the mid-term impact of HMP in patients receiving expanded criteria donor (ECD) kidneys. Methods The analyses were based on the French Données Informatisées et VAlidées en Transplantation (DIVAT) observational cohort. Patients aged ≥45 years transplanted for the first or second times from an ECD donor since 2010 were studied. Our study reported the graft and/or patient survivals and the incidence of acute rejection episode. The Cox models and the Kaplan–Meier estimators, weighted on the propensity score, were used to study the times-to-events. Results Among the 2019 included patients, 1073 were in the SCS group versus 946 in the HMP group. The mean life expectancy with functioning graft was 5.7 years [95% confidence interval (CI) 5.4–6.1] for the HMP cohort followed-up for 8 years post-transplantation versus 6.0 years (95% CI 5.7–6.2) for the SCS group. These mid-term results were comparable in the patients receiving grafts from donors aged ≥70 years and in the transplantations with cold ischaemia time ≥18 h. Conclusions Our study challenges the utility of using HMP to improve mid-term patient and graft survival. Nevertheless, the improvement of the short-term outcomes is indisputable. It is necessary to continue technological innovations to obtain long-term results

The EKiTE network (epidemiology in kidney transplantation - a European validated database): an initiative epidemiological and translational European collaborative research

BACKGROUND: Kidney transplantation is considered to be the treatment of choice for people with end-stage renal disease (ESRD). However, due to the shortage of available organs and the increase in the ESRD prevalence in Europe, it is essential to improve transplantation outcomes by studying the related prognostic factors. Today, there is no European registry collecting data to perform such clinical epidemiology studies. MAIN BODY: Entitled EKiTE, for European cohort for Kidney Transplantation Epidemiology, this prospective and multicentric cohort includes patients from Spanish (Barcelona), Belgian (Leuven), Norwegian (Oslo) and French (Paris Necker, Lyon, Nantes, Nancy, Montpellier, Nice and Paris Saint Louis) transplantation centers and currently contains 13,394 adult recipients of kidney (only) transplantation from 2005 and updated annually. A large set of parameters collected from transplantation until graft failure or death with numbers of post-transplantation outcomes. The long-term follow-up and the collected data enable a wide range of possible survival and longitudinal analyses. CONCLUSION: EKiTE is a multicentric cohort aiming to better assess the natural history of the ESRD in European kidney transplant recipients and perform benchmarking of clinical practices. The data are available for clinical epidemiology studies and open for external investigators upon request to the scientific council. Short-term perspectives are to extend EKITE network to other European countries and collect additional parameters in respect of the common thesaurus.status: publishe

Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients

International audienceThe aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. A total of 1,621 infected patients were reported on the REIN registry from March 16th, 2020 to May 4th, 2020. Of these, 344 died. The prevalence of COVID-19 patients varied from less than 1% to 10% between regions. The probability of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Dialysis at home was associated with a lower probability of being infected as was being a smoker, a former smoker, having an active malignancy, or peripheral vascular disease. Mortality in diagnosed cases (21%) was associated with the same causes as in the general population. Higher age, hypoalbuminemia and the presence of an ischemic heart disease were statistically independently associated with a higher risk of death. Being treated at a selfcare unit was associated with a lower risk. Thus, our study showed a relatively low frequency of COVID-19 among dialysis patients contrary to what might have been assumed