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We conducted a retrospective study on hemolytic uremic syndrome caused by Shiga toxin-producing Escherichia coli (STEC) in 96 adults enrolled in the cohort of the National Reference Center for Thrombotic Microangiopathies network in France during 2009-2017. Most infections were caused by STEC strains not belonging to the O157 or O104 serogroups. Thirty (31.3%) patients had multiple risk factors for thrombotic microangiopathy. In total, 61 (63.5%) patients required dialysis, 50 (52.1%) had a serious neurologic complication, 34 (35.4%) required mechanical ventilation, and 19 (19.8%) died during hospitalization. We used multivariate analysis to determine that the greatest risk factors for death were underlying immunodeficiency (hazard ratio 3.54) and severe neurologic events (hazard ratio 3.40). According to multivariate analysis and propensity score-matching, eculizumab treatment was not associated with survival. We found that underlying conditions, especially immunodeficiency, are strongly associated with decreased survival in adults who have hemolytic uremic syndrome caused by STEC.

Background: Atypical hemolytic uremic syndrome (HUS) is associated with high recurrence rates after kidney transplant, with devastating outcomes. In late 2011, experts in France recommended the use of highly individualized complement blockade-based prophylaxis with eculizumab to prevent post-transplant atypical HUS recurrence throughout the country., Methods: To evaluate this strategy's effect on kidney transplant prognosis, we conducted a retrospective multicenter study from a large French nationwide registry, enrolling all adult patients with atypical HUS who had undergone complement analysis and a kidney transplant since January 1, 2007. To assess how atypical HUS epidemiology in France in the eculizumab era evolved, we undertook a population-based cohort study that included all adult patients with atypical HUS ( n =397) between 2007 and 2016., Results: The first study included 126 kidney transplants performed in 116 patients, 58.7% and 34.1% of which were considered to be at a high and moderate risk of atypical HUS recurrence, respectively. Eculizumab prophylaxis was used in 52 kidney transplants, including 39 at high risk of recurrence. Atypical HUS recurred after 43 (34.1%) of the transplants; in four cases, patients had received eculizumab prophylaxis and in 39 cases they did not. Use of prophylactic eculizumab was independently associated with a significantly reduced risk of recurrence and with significantly longer graft survival. In the second, population-based cohort study, the proportion of transplant recipients among patients with ESKD and atypical HUS sharply increased between 2012 and 2016, from 46.2% to 72.3%, and showed a close correlation with increasing eculizumab use among the transplant recipients., Conclusions: Results from this observational study are consistent with benefit from eculizumab prophylaxis based on pretransplant risk stratification and support the need for a rigorous randomized trial., (Copyright © 2019 by the American Society of Nephrology.)

Secondary hemolytic uremic syndrome (HUS) is a heterogeneous group of thrombotic microangiopathies associated with various underlying conditions. Whether it belongs to the spectrum of complement-mediated HUS remains controversial. We analysed the presentation, outcome, and frequency of complement gene rare variants in a cohort of 110 patients with secondary HUS attributed to drugs (29%), autoimmune diseases (24%), infections (17%), malignancies (10%), glomerulopathies (9%), extra-renal organ transplantation (8%), and pancreatitis (3%). The frequency of complement gene rare variants was similar in patients with secondary HUS (5%) and in healthy individuals (6% and 8% in French and European controls, respectively). At diagnosis, 40% of patients required dialysis and 18% had neurological manifestations. Fifty percent of patients received plasmatherapy and 35% were treated with eculizumab. Haematological and complete renal remission was achieved in 80% and 24% of patients, respectively. Thirty-nine percent of patients progressed to chronic kidney disease (stages 3-4) and an additional 37% reached end-stage renal disease. Eleven percent of patients died, most often from complications of the underlying cause of HUS. Only one patient experienced an HUS relapse. Patients treated with eculizumab presented with more severe HUS and were more likely to require dialysis at the time of diagnosis as compared to patients not treated with eculizumab. Rates of hematological remission, chronic kidney disease (stages 3-4), and end-stage renal disease were similar in the two groups. Secondary HUS is an acute nonrelapsing form of HUS, not related to complement dysregulation. The efficacy of eculizumab in this setting is not yet established., (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

This French multicenter retrospective cohort study aimed to describe the autoimmune manifestations (AIMs) associated with lymphoma among patients hospitalized between 2005 and 2016 in three French University Hospitals. Among 2503 patients with lymphoma, 108 (4.3%) had AIMs, mostly autoimmune cytopenias (71.3%), neurological diseases (10.2%), kidney diseases (6.5%), systemic vasculitis (5.6%) and others. As compared with the 2395 lymphoma patients without AIMs, those with AIMs were older (p = .01), more frequently had B-cell chronic lymphocytic leukemia (p < .01) and less frequently diffuse large B-cell lymphomas (p = .01) and Hodgkin lymphoma (p = .01). The 5-year overall survival with lymphoma was 65% and 79% (p = .03) with and without AIMs. This large cohort study shows that various types of AIMs, mostly cytopenias, could be associated with lymphoma and affect the overall outcome with lymphoma, in particular for B-cell non-Hodgkin lymphoma (p = .01) and T-cell non-Hodgkin lymphoma (p = .01), with no survival difference noted for other types of lymphoma (p = .2).

Background: Thrombotic thrombocytopenic purpura is a thrombotic microangiopathy related to a severe deficiency of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13; activity <10%). We aimed to investigate the association between mechanisms for ADAMTS13 deficiency and the epidemiology and pathophysiology of thrombotic thrombocytopenic purpura at initial presentation., Methods: Between Jan 1, 1999, and Dec 31, 2013, we did a cross-sectional analysis of the French national registry for thrombotic microangiopathy to identify all patients with adult-onset thrombotic microangiopathy (first episode after age 18 years) who had severe ADAMTS13 deficiency at presentation. ADAMTS13 activity, anti-ADAMTS13 IgG, and ADAMTS13 gene mutations were investigated by a central laboratory. We collected patients' clinical data for correlation with their ADAMTS13 phenotype and genotype. We used logistic regression analysis to identify variables significantly associated with idiopathic thrombotic thrombocytopenic purpura, as measured by estimated odds ratios (ORs) and 95% CIs. This study is registered with ClinicalTrials.gov, number NCT00426686., Findings: We enrolled 939 patients with adult-onset thrombotic thrombocytopenic purpura, of whom 772 (82%) patients had available data and samples at presentation and comprised the cohort of interest. The prevalence of thrombotic thrombocytopenic purpura in France was 13 cases per million people. At presentation, 378 (49%) patients had idiopathic thrombotic thrombocytopenic purpura, whereas 394 (51%) patients had disease associated with miscellaneous clinical situations (infections, autoimmunity, pregnancy, cancer, organ transplantation, and drugs). Pathophysiologically, three distinct forms of thrombotic thrombocytopenic purpura were observed: 585 (75%) patients had autoimmune disease with anti-ADAMTS13 IgG, 166 (22%) patients had acquired disease of unknown cause and 21 (3%) patients had inherited disease (Upshaw-Schulman syndrome) with mutations of the ADAMTS13 gene. Idiopathic thrombotic thrombocytopenic purpura were mainly autoimmune (345 [91%] cases), whereas non-idiopathic diseases were heterogeneous, including a high rate of unexplained mechanisms for ADAMTS13 deficiency (133 [34%] cases). Obstetrical thrombotic thrombocytopenic purpura cases (n=62) were specifically remarkable because of the high rate of patients with Upshaw-Schulman syndrome (21 [34%] patients)., Interpretation: Our study shows that thrombotic thrombocytopenic purpura is a heterogeneous syndrome, and that features of the disease at presentation are strongly associated with the mechanisms of ADAMTS13 deficiency. In addition to mechanistic insight, our findings could have implications for the initial therapeutic management of patients with this disorder., Funding: Assistance Publique-Hôpitaux de Paris., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Infectious events have been reported as major environmental triggers of thrombotic thrombocytopenic purpura (TTP). We detail here the potential association between infections and TTP., Study Design and Methods: We recruited randomly and prospectively a cohort of 280 consecutive TTP patients during a 9-year period. Features of infection were systematically recorded., Results: Features consistent with an infectious event were observed in 114 patients (41%) at time of TTP diagnosis. Infectious agents were documented in 34 cases and were mainly Gram-negative bacilli. At time of diagnosis infected patients more frequently had fever (p < 0.001). Infections at diagnosis did not impact prognosis and outcome. Thirty-six percent of patients experienced an infectious event during hospitalization, which resulted in more exacerbation of TTP (p = 0.02). Infections were not overrepresented during treatment in patients who received steroids and/or rituximab. Further genetic analysis of toll-like receptor (TLR)-9 functionally relevant polymorphisms revealed that TLR-9 +2848 G and TLR-9 +1174 A genotypes were more frequent in TTP patients than in controls (p = 0.04 and p = 0.026, respectively) and more particularly in patients negative for the Class II human leukocyte antigen system susceptibility allele DRB1*11 (p = 0.001 and p = 0.002, respectively). Haplotypes estimation showed that 1174A-2848G haplotype was significantly more frequent in TTP (p = 0.004), suggesting a primary role for this haplotype variation in conferring a predisposition for acquired TTP., Conclusion: Infections should be considered as an aggravating factor during the course of TTP. Particular polymorphisms in TLR-9 gene may represent risk factors for TTP., (© 2013 American Association of Blood Banks.)

Background and Objectives: The therapy and outcome of HIV infection have dramatically changed over the last 15 years, resulting in a change in renal complications. This study analyzed the characteristics of HIV-infected patients and biopsy-proven tubulointerstitial nephropathies to define disease patterns and therapeutic implications., Design, Setting, Participants, & Measurements: A clinico-pathologic retrospective study of 59 consecutive renal biopsies showing predominant tubular and/or interstitial lesions in HIV-infected patients referred to the nephrology department between 1995 and 2011 was performed. HIV-associated nephropathy and vascular diseases were excluded from the study., Results: Tubulointerstitial nephropathies accounted for 26.6% of 222 native renal biopsies performed in HIV-infected patients. Two pathologic groups were analyzed, tubulopathy and interstitial nephritis, which represented 49% and 51% of tubulointerstitial nephropathies, respectively. Most patients presented with AKI (76.3%) and high-grade proteinuria (57.7%). Drug-related nephrotoxicity was the leading cause (52.5%). Alternative etiologies included infections (15.2%), dysimmune disorders (8.5%), malignancies (3.4%), and chronic (10.2%) and acute (10.2%) tubulointerstitial nephropathies of undetermined origin. Tubulopathy was strongly associated with antiretroviral drug toxicity (75.9%) and mostly caused by tenofovir (55.2%), which was associated with proximal tubular dysfunction (87.5%), overt Fanconi's syndrome (37.5%), and nephrogenic diabetes insipidus (12.5%). Interstitial nephritis was associated with a broader spectrum of pathologic lesions and etiologies., Conclusions: In this series, tubulointerstitial nephropathies accounted for 26.6% of renal diseases in HIV-infected patients. Considering the therapeutic implications of diagnoses of drug toxicity, infection, and dysimmune syndromes, this study underscores the importance of monitoring renal parameters in HIV-infected patients and points to the relevance of kidney biopsy to allow an accurate diagnosis.

Background: Acute pulmonary oedema (APO) in patients undergoing chronic dialysis (CD), a common cause of hospital admission in this population, is poorly documented. The objective of this study was to determine the causes, profile, clinical course and outcomes of APO in CD patients admitted in an intensive care unit (ICU)., Methods: Medical charts of all CD patients consecutively admitted for APO in the renal ICU of the Tenon Hospital (Paris, France) between January 2000 and December 2007 were considered. Data collection included patient characteristics, etiologic factors for chronic renal failure and co-morbidities, past history of APO, precipitating factors, clinical evolution and outcomes., Results: Of the 112 files considered, 102 (65% men) were included in the final analysis. Patients were aged 20-88 years and had been dialysed for a median duration of 2 years. Hypertension (36.3%), chronic glomerulonephritis (25.5%) and diabetes mellitus (17.6%) were the main etiologic factors of chronic renal failure; 38.2% had a past history of APO. Acute pulmonary infection (26%), excessive interdialytic weight gain (25%) and inappropriate dry weight prescription (23%) were the leading causes of APO. The duration of hospitalization was <4 days in 60% of participants. Nine deaths (four being of cardiac origin) were recorded. Being referred from another hospital service was the main predictor of death., Conclusions: APO fuelled in part by chest infection, excessive interdialytic weight gain and inappropriate dry weight are important causes of hospitalization in CD patients. Mortality is high among those referred from other services usually in critical conditions.

Background: In 1997, 0.38% of dialysis patients in France were infected by human immunodeficiency virus (HIV). No prevalence data were available in France since the widespread introduction of highly active antiretroviral therapy., Methods: This was a cross-sectional epidemiologic survey. A questionnaire was sent to all French dialysis centers in July 2002. The centers that did not respond were sent 3 additional mailing reminders. Finally, the nonresponding centers were called early in 2004., Results: Of the 27,577 patients on hemodialysis and 587 patients on peritoneal dialysis, 190 patients (0.67%) were infected by HIV. HIV-associated nephropathy was the cause of renal failure in 39.8% patients. Mean age was 44.6 +/- 10.9 years, the mean duration of dialysis was 4.9 +/- 5.9 years, the mean known duration of HIV infection was 8.9 +/- 5.6 years. Eighty-two percent of patients received antiretroviral therapy (ART). Fifty-eight percent of ART-treated patients had an undetectable HIV plasma viral load with a median CD4+ T-cell count 303/mm(3)., Conclusion: The prevalence of HIV infection among French dialysis patients was 0.67% in late 2002, a 79% increase since 1997. Possible reasons for this large increase include increased access to dialysis, better general status of HIV dialysis patients, and increasing proportion of patients originating from Africa and the Caribbean. The current efficacy of ART makes renal transplantation a realistic option for these young patients.

Parameters of early failure in kidney transplantation have been analyzed from 507 transplantations with transplant loss in the first month, selected among the 7541 cadaveric kidney transplantations performed in France between 1985 and 1989. These failures represent 6.7 percent of the population transplanted over this period of time, 68.6 percent of the failures that occurred in the first 3 months post-grafting, and 47 percent of the total number of the first year failures. Comparing patients with and without transplant failure in the first month, sex of the donor and the recipient, ABO group of the donor and the recipient, origin of the kidney, cold ischemia time, HLA compatibility, dialysis duration, number of previous transplantations, showed no influence on the occurrence of early failure. Three parameters appeared to be significant risk factors: donor's age less than 5 years, P = 0.00001; recipient's age less than 5 years, P = 0.05; pregraft immunization, P = 0.002. Furthermore, multifactorial analysis showed that the absence of HLA compatibilities between donor and recipient in hyperimmunized patients also has a significant influence on early graft loss. However, comparison of these same parameters in patients with transplant failure within the first month and between 2 and 12 months post-grafting revealed that the influence of these 4 significant parameters is longstanding and that none of them is specific of the precocity of graft loss.