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Background Anti-neutrophil cytoplasmic antibody (ANCA) kinetic in ANCA-associated vasculitis with glomerulonephritis (AAV-GN) has been suggested to be associated with AAV relapse. Few studies have focused on its association with renal prognosis. Thus we aimed to investigate the relationship between ANCA specificity and the evolutive profile and renal outcomes. Methods This multicentric retrospective study included patients diagnosed with ANCA-GN since 1 January 2000. Patients without ANCA at diagnosis and with fewer than three ANCA determinations during follow-up were excluded. We analysed estimated glomerular filtration rate (eGFR) variation, renal-free survival and relapse-free survival according to three ANCA profiles (negative, recurrent and persistent) and to ANCA specificity [myeloperoxidase (MPO) or proteinase 3 (PR3)]. Results Over a follow-up of 56 months [interquartile range (IQR) 34–101], a median of 19 (IQR 13–25) ANCA determinations were performed for the 134 included patients. Patients with a recurrent/persistent ANCA profile had a lower relapse-free survival (P = .019) and tended to have a lower renal survival (P = .053) compared with those with a negative ANCA profile. Patients with a recurrent/persistent MPO-ANCA profile had the shortest renal survival (P = .015) and those with a recurrent/persistent PR3-ANCA profile had the worst relapse-free survival (P = .013) compared with other profiles. The negative ANCA profile was associated with a greater eGFR recovery. In multivariate regression analysis, it was an independent predictor of a 2-fold increase in eGFR at 2 years [odds ratio 6.79 (95% confidence interval 1.78–31.4), P = .008]). Conclusion ANCA kinetic after an ANCA-GN diagnosis is associated with outcomes. MPO-ANCA recurrence/persistence identifies patients with a lower potential of renal recovery and a higher risk of kidney failure, while PR3-ANCA recurrence/persistence identifies patients with a greater relapse risk. Thus ANCA kinetics may help identify patients with a smouldering disease.

Objective: To assess the impact of an oocyte retrieval simulation training program (ORSTP) on the clinical performance of residents. Design: Prospective comparative study. Setting: A tertiary care center. Population: All OR performed by residents between May 2018 and November 2021. Methods & main outcome measures: The Simulation (S) group included oocyte retrieval (OR) performed by residents who had undergone an ORSTP before performing them on patients (n=422) and the control (C) group included OR performed by residents who had not received prior simulation training (n= 329). Our main outcome measure was the OR rate (ORR) (number of oocytes collected/number of follicles aspirated) during the first 3 months of the rotation. Results: In the S group, 6 residents aspirated 657 ovaries while in the C group, 5 residents aspirated 508 ovaries. The mean ORR during the first 3 months of rotation were comparable between the S and C groups (59% (2800/472) vs 58% (1910/3281)). ORR during the first and second month, and at the end of the rotation were also comparable between the S and C groups (54% vs 63%, 58% vs 59% and 58% vs 58%, respectively). There was no significant difference in the rate of failed OR (3.3% vs 1.8%) between the S and C groups. Finally, 16% of residents in the S group reported being stressed before their first OR compared to 40% in the C group. Conclusions: The ORSTP does not improve the residents’ clinical performance, but it could decrease their stress in clinical practice. Keywords: oocyte pick-up, infertility, simulation, education, student.

Objective: To assess the impact of an oocyte retrieval simulation training program (ORSTP) on the clinical performance of residents. Design: Prospective comparative study. Setting: A tertiary care center. Population: All OR performed by residents between May 2017 and November 2020. Methods & main outcome measures: The Simulation (S) group included OR performed by residents who had undergone an ORSTP before performing them on patients (n=422) and the control (C) group included OR performed by residents who had not received prior simulation training (n= 329). Our main outcome measure was the OR rate (ORR) (number of oocytes collected/number of follicles aspirated) during the first 3 months of the rotation. Results: In the S group, 6 residents aspirated 657 ovaries while in the C group, 5 residents aspirated 508 ovaries. The mean ORR during the first 3 months of rotation were comparable between the S and C groups (59% vs 58%). ORR during the first and second month, and at the end of the rotation were also comparable between the S and C groups (54% vs 63%, 58% vs 59% et 58% vs 58%, respectively). There was no significant difference in the rate of failed OR (3.3% vs 1.8%) between the S and C groups. Finally, 16% of residents in the S group reported being stressed before their first OR compared to 40% in the C group. Conclusions: The ORSTP does not improve the residents’ clinical performance, but it could decrease their stress in clinical practice.

Background and Aims Lymphopenia is commonly observed in various autoimmune diseases, such as systemic lupus erythematosus, where it has been associated with disease activity or prognosis. However, in ANCA-associated vasculitis (AAV) only few, small-scale studies have been targeted to this issue. Research has not yet focused on ANCA-glomerulonephritis (ANCA-GN) patients. Thus, the aim of this study was to analyze the association between lymphocyte counts and outcomes in a large cohort of ANCA-GN patients. Method We used the Maine-Anjou AAV registry that retrospectively gathers data on consecutive patients affected by AAV in four French Nephrology Centers, recorded since January 2000. We analyzed clinical, biological, and histological data at diagnosis of ANCA-GN. Biological data, including lymphocyte counts, were collected before the administration of any immunosuppressive treatment. Risk factors for end-stage kidney disease (ESKD) were analyzed. Event-free survival was also assessed. Results Among the 145 patients included in the study, 53 (37%) patients presented with lymphopenia at ANCA-GN diagnosis. Lymphopenic patients were older (72 [63–79] vs 66 [56–73] years old, p = 0.010), had a lower renal function at baseline (eGFR 13 mL/min vs 26 mL/min, p = 0.002), and a higher proteinuria (1.86 [1.21–3.52] g/g vs 1.30 [0.75–2.65] g/g, p = 0.042). There was a trend for a higher BVAS (18 [14–22] vs 15 [12–20], p = 0.076) in lymphopenic patients. Therapeutic management between the two groups was similar. There was no difference in relapse rate between the two groups but lymphopenic patients were more likely to require kidney replacement therapy (51% vs 25%, p = 0.003) and were more likely to die (34% vs 17%, p = 0.039). Lymphopenia was correlated with histological lesions and especially with the percentage of sclerotic glomeruli (p = 0.0027). ESKD-free survival and overall survival were lower in lymphopenic patients (p < 0.0001 and 0.0051 respectively). In multivariate Cox analysis, lymphopenia, but not death, was an independent risk factor for ESKD (HR 4.47 (95% confidence interval: [2.06–9.72], p < 0.001). Conclusion Lymphopenia correlates with severity of ANCA-GN at diagnosis and predicts poor renal outcome. In this view, lymphopenia could be used as a simple and cost-effective biomarker to assess renal prognosis at ANCA-GN diagnosis.

Systemic lupus erythematosus (SLE) is a systemic and potentially fatal autoimmune disease. SLE pathophysiology is complex and involves the interplay between the innate and adaptive immune systems, with a particularly significant role for type I interferons. Recently, the participation of other actors such as platelets and IgE has been described in SLE. On the one hand, platelets activated by different stimuli (antiphospholipid antibodies, immune complexes…) participate in immune dysregulation through direct interactions with immune cells. On the other hand, autoreactive IgE can activate basophils, promoting a Th2 environment and subsequent antibody production by plasma cells. In synergy with IgG, IgE is also able to activate plasmacytoid DCs (pDCs) increasing interferon alpha production. Mirroring the IgG paradox, total nonautoreactive IgE is described as a potential regulator of IFNα production. This review summarizes recent and novel data on innate immunity in SLE pathophysiology with a focus on platelets and IgE, as they represent novel players in immune dysregulation and potential therapeutic targets.

Background Lymphopaenia is commonly observed in autoimmune diseases, where it has been associated with disease activity or prognosis. However, in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) only a few small-scale studies have been targeted towards this issue. Research has not yet focused on AAV with renal involvement (AAV-RI). Thus the aim of this study was to analyse the association between lymphocyte counts and outcomes in a large cohort of AAV-RI patients. Methods We used the Maine-Anjou AAV registry that retrospectively gathers data on consecutive patients affected by AAV in four French nephrology centres, recorded since January 2000. We analysed clinical, biological and histological data at diagnosis of AAV-RI. Risk factors for end-stage kidney disease (ESKD) were analysed. Event-free survival was also assessed. Results Among the 145 patients included in the study, those with lymphopaenia at diagnosis had a lower renal function at baseline [estimated glomerular filtration rate (eGFR) 13 versus 26 mL/min; P = 0.002] and were more likely to require kidney replacement therapy (51% versus 25%; P = 0.003). Lymphopaenia was correlated with histological lesions and especially with the percentage of sclerotic glomeruli (P = 0.0027). ESKD-free survival was lower in lymphopaenic patients (P Conclusions Lymphopaenia correlates with the severity of AAV glomerulonephritis at diagnosis and predicts poor renal outcome. In this view, lymphopaenia could be used as a simple and cost-effective biomarker to assess renal prognosis at AAV-RI diagnosis.

(1) Introduction: The incidence of venous thromboembolisms (VTE) has not been extensively analyzed in patients with antineutrophil cytoplasmic antibody (ANCA)-glomerulonephritis (ANCA-GN). Thus, the aim of the present study was to assess the frequency and the risk factors of VTE in patients with ANCA-GN. (2) Methods: Patients from the Maine-Anjou ANCA-associated vasculitis (AAV) registry with a biopsy showing pauci-immune glomerulonephritis were included. VTE events, site, and interval from AAV diagnosis were analyzed. (3) Results: 133 patients fulfilled the inclusion criteria of the study and were analyzed. VTE episodes were diagnosed in 23/133 (17.3%) patients at a median delay of 3 months from ANCA-GN diagnosis. Patients with VTE had lower serum albumin (p = 0.040), were less frequently on statin therapy (p = 0.009) and had less frequently proteinase-3 (PR3)-ANCAs (p = 0.078). Univariate analysis identified higher age (p = 0.022), lower serum albumin (p = 0.030), lack of statin therapy (p = 0.009), and rituximab treatment (p = 0.018) as significant risk factors of VTE. In multivariate analysis, only lack of statin therapy (HR 4.873, p = 0.042) was significantly associated with VTE. (4) Conclusion: Patients with ANCA-GN are at high risk of VTE, especially within the first months following AAV diagnosis. Our results suggest that statin therapy is associated with a lower risk of VTE in ANCA-GN patients.

Background: Thrombotic microangiopathies (TMAs) are highly suspected in patients showing mechanical hemolytic anemia, thrombocytopenia, and haptoglobin consumption. Primary [thrombotic thrombocytopenic purpura (TTP) and atypical hemolytic uremic syndrome] and secondary TMA are considered. Even if ADAMTS13 measurements and alternative complement pathway explorations have greatly improved the ability to identify primary TMA, their diagnosis remains difficult, and their frequency relative to that of secondary TMA is undetermined. The objectives of the present study were, therefore, to describe the etiologies, management, and the outcomes of patients presenting with TMA in real-life clinical practice.Methods: We conducted a retrospective study between 01/01/2008 and 31/12/2018 that included all consecutive patients presenting with biological TMA syndrome at admission or developing during hospitalization. Patients were identified from the laboratory databases, and their medical files were reviewed to confirm TMA diagnosis, to determine etiology, and to analyze their therapeutic management and outcomes.Results: During this period, 239 patients with a full TMA biological syndrome were identified, and the TMA diagnosis was finally confirmed in 216 (90.4%) after the cases were reviewed. Primary TMAs (thrombotic thrombocytopenic purpura or atypical hemolytic uremic syndrome) were diagnosed in 20 of 216 patients (9.3%). Typical HUS was diagnosed in eight patients (3.7%), and the most frequent secondary TMAs were HELLP syndrome (79/216, 36.6%) and active malignancies (30/219, 13.9%). ADAMTS13 measurements and alternative complement pathway analyses were performed in a minority of patients. Multiple factors identified as TMA triggers were present in most patients, in 55% of patients with primary TMA, vs. 44.7% of patients with secondary TMA (p = 0.377). Death occurred in 57 patients (23.4%) during follow-up, and dialysis was required in 51 patients (23.6%). Active malignancies [odds ratio (OR) 13.7], transplantation (OR 4.43), male sex (OR 2.89), and older age (OR 1.07) were significantly associated with death.Conclusion: Secondary TMAs represent many TMA causes in patients presenting a full TMA biological syndrome during routine clinical practice. Multiple factors favoring TMA are present in about half of primary or secondary TMA. ADAMTS13 and complement pathway were poorly explored in our cohort. The risk of death is particularly high in patients with malignancies as compared with patients with other TMA.

International audience; Purpose: Data regarding the long-term outcome of very elderly (VE) patients undergoing renal biopsy (RB) are lacking. The objective of this study was to analyse the outcome of VE patients undergoing RB.Methods: All patients over 65 years that underwent native RB between 2004 and 2016 in our center were included. Among the 206 included patients, those over 80 years (VE, 46 patients) were analysed and compared to those aged 65-80 years (160 patients). The outcomes of the VE group were analysed.Results: Baseline characteristics, renal presentation, safety of RB and RB-related diagnosis were not different between VE patients and 65-80-year-old patients. Survival of VE patients was 73.1, 50.6 and 21.8% at 2, 4 and 6 years after RB, significantly poorer than those of 65-80-year-old group. Early death (< 1 year) occurred in 10 VE patients, was associated with a higher proteinuria-to-creatininuria ratio and tended to be associated with a more frequent dialysis need at RB. Of the 46 VE patients, 31 (67.4%) were diagnosed with a potentially reversible kidney disease, of whom 17 (40%) were started on immunosuppressive regimens. Survival of patients with a reversible kidney disease tended to be better than those with other diseases.Conclusion: RB appears as a safe and valuable procedure to assess diagnosis of kidney disease in VE patients. Our data suggest that RB is critical for the identification and treatment decision of patients with potentially reversible diseases and may translate in clinical improvement.

International audience; Anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitides (AAVs) are small vessel vasculitides involving predominantly ear-nose-throat, kidneys, lungs and nerves. AAVs are life-threatening diseases, especially in their most severe forms such as necrotizing crescentic glomerulonephritis (GN) and/or intra-alveolar hemorrhage. Unlike immune complex GN or anti-glomerular basement membrane GN, AAVs are classified as pauci-immune GN. However, based on recent insights from animal models, the view of AAVs as a complement-unrelated disease has been challenged. Indeed, complement activation, and especially complement alternative pathway (cAP) activation, has been shown to be determinant in AAV pathogenesis through C5a generation, a potent chemoattractant for neutrophils with priming capacities. Here, we review in vitro and in vivo data supporting the role of cAP in murine models and in human AAVs. These findings, together with the need to eradicate glucocorticoid toxicity, led to the development of an anti-C5aR molecule, CCX168, also known as avacopan. Its development and future opportunities are also discussed.

Introduction Les patientes aux antecedents de preeclampsies (PE) sont plus a risque d’insuffisance renale chronique (IRC) terminale que les femmes sans antecedent de dysgravidie. L’origine de cette IRC est mal connue. Description Nous decrivons ici la mise en place dans notre centre d’une consultation nephrologique systematique, post desordre hypertensif lie a la grossesse (DHG). Methodes Toutes les patientes ayant presente un DHG ont ete dirige en consultation de nephrologie 3 mois apres l’accouchement. Un bilan biologique standardise etait realise, couple a une echographie renale. Resultats Au terme de 2 ans de suivi, 127 patientes ont ete vues en consultation nephro-obstetricale, 46 consultations n’ayant pas ete honorees. L’âge median etait de 31 ans (27,5-35), pour un diagnostic de PE porte a un terme median de 34 SA (30,1-37,3), 67 patientes (54 %) ayant presentees une PE precoce (≤ 34SA). Le diagnostic de maladie renale chronique (MRC) a ete pose chez 18 patientes (14 %) : 8 stade I et 10 stade II. Une HTA persistante etait notee chez 15 patientes (12 %) dont 5 hyperaldosteronismes primaires et un pheochromocytome. Un lupus, 4 syndromes des antiphospholipides (SAPL) (3,2 %), 3 mutations du facteur V (2,4 %) et 10 du gene de la prothrombine (8,1 %) ont egalement ete mis en evidence. Au total, un diagnostic etait pose chez 43 des 127 patientes (33 %) dans les suites de la consultation et au moins une anomalie biologique significative retrouvee chez 62 (49 %) des patientes. On ne retrouvait pas de difference en terme de diagnostic en distinguant les patientes avec PE precoce (≤ 34SA) des tardives (> 34SA). Conclusion La detection de MRC, d’HTA, de maladies auto-immunes ou thombophiliques est frequente chez les patientes ayant presentees un DHG. La precocite ou la severite de la PE ne semble pas influer sur l’incidence du diagnostic. Un suivi nephrologique systematique de toutes les patientes ayant presente un DHG est necessaire.

Introduction La lymphopenie est classiquement retrouvee dans certaines maladies auto-immunes tels que le lupus erythemateux dissemine, ou elle est associee a l’activite de la maladie et au pronostic global. Dans le cadre des vascularites a ANCA (AAV), la lymphopenie a ete peu etudiee. Description Nous avons analyse l’association entre la presence d’une lymphopenie au diagnostic d’AAV avec atteinte renale (glomerulonephrite a ANCA, ANCA-GN) et le pronostic renal. Methodes Nous avons analyse retrospectivement les donnees cliniques, biologiques et histologiques des patients avec ANCA-GN inclus entre 2000 et 2020 dans le registre multicentrique « Maine-Anjou ». Le compte lymphocytaire a ete recupere avant l’administration de tout traitement immunosuppresseur. Resultats Parmi les 145 patients inclus dans l’etude, 53 (37 %) presentaient une lymphopenie au diagnostic. Les patients lymphopeniques etaient plus âges (72 ans vs 66 ans, p = 0,010), avaient une moins bonne fonction renale au diagnostic (eGFR 13 vs 26 mL/min, p = 0,002), et etaient plus proteinuriques (1,86 vs 1,30 g/g, p = 0,042). Au terme d’un suivi median de 36 mois, les patients lymphopeniques evoluaient plus souvent vers l’insuffisance renale terminale (IRT) (51 % vs 25 %, p = 0,003) et mourraient plus (34 % vs 17 %, p = 0,039). La lymphopenie au diagnostic etait correlee aux lesions histologiques renales en particulier au pourcentage de glomerules sclereux (p = 0,0027). La survie sans IRT etait moins bonne chez les patients lymphopeniques. En analyse de Cox multivariee, la lymphopenie etait un facteur de risque independant d’evolution vers l’IRT (HR : 4,47, IC95 % : 2,06–9,72, p Conclusion La lymphopenie au diagnostic d’ANCA-GN est correlee avec sa severite et pourrait etre utilisee comme marqueur simple et peu couteux pour l’evaluation du pronostic renal.

International audience; Background and objectives: The overlap between antineutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis (ANCA-GN) and connective tissue diseases (CTD) has been reported mainly as case series in the literature. Frequency of this association, as well as presentation and outcomes are unknown. Materials and Methods: Patients from the Maine-Anjou ANCA-associated vasculitides (AAV) registry with ANCA-GN diagnosed between 01/01/2000 and 01/01/2018, ANCA positivity, and at least six months of follow-up, were included. Results: 106 out of 142 patients fulfilled the inclusion criteria and were analyzed. CTD was present at ANCA-GN diagnosis in 16 (15.1%) patients. The most common CTD were rheumatoid arthritis, Sjogren syndrome and systemic sclerosis. Compared to the control group, females were more represented in the CTD group (75%, p = 0.001). Renal presentation was comparable between groups, including the pathological analysis of renal biopsies. Patients of CTD group presented a higher rate of non-renal relapse (25% versus 7.7%, p = 0.037), and experienced more frequently a venous thrombotic event (31.2% versus 10%, p = 0.021). No difference between groups was observed according to major outcomes. Conclusion: Association between CTD and ANCA-GN is not a rare condition and predominantly affects females. While AAV presentation is not significantly different, CTD patients experience more frequently non-renal relapse and venous thrombotic events.

Introduction L’exposition chronique a la silice peut entrainer une silicose pulmonaire associee ou non a des maladies auto-immunes (polyarthrite rhumatoide, sclerodermie, vascularites a ANCA). La physiopathologie des maladies auto-immunes induites par la silice n’est pas bien determinee. Methodes Nous avons mene une etude prospective pour analyser l’impact de l’exposition a la silice sur la production d’auto-anticorps et sur le phenotype des lymphocytes T circulants chez des sujets exposes a la silice sans silicose pulmonaire reconnue. Dans des entreprises produisant des revetements pour le bâtiment, nous avons recrute des sujets âges de trente a soixante ans avec une exposition moderee a elevee a la silice. Le phenotype des lymphocytes T a ete analyse par cytometrie et les auto-anticorps (anti-nucleaires et ANCA) ont ete recherches par methodes classiques. Resultats obtenus ou attendus Parmi les 55 sujets recrutes, 10 furent exposes moins de 5 ans, 18 entre 5 et 10 ans et 27 plus de 10 ans ; 42 prelevements de donneurs sains non exposes furent inclus comme temoins. Nous montrons : – une augmentation significative de l’expression du marqueur d’activation HLA-DR sur les lymphocytes T (CD3+, CD4+ ou CD8 + ) des sujets exposes a la silice comparativement aux sujets non exposes ; l’augmentation est d’autant plus importante que la duree d’exposition est longue ; – une diminution significative de la frequence des lymphocytes T regulateurs (CD4 + CD25 + CD127-FoxP3 + ). Parmi les sujets exposes plus de 10 ans, 44 % presentaient des ANA et 22 % des ANCA, comparativement a 5 % et 2,5 % respectivement dans le groupe temoin. Conclusion Nous montrons que l’exposition a la silice est associee a une rupture de la tolerance immunitaire avec diminution des lymphocytes T regulateurs et augmentation de l’activation lymphocytaire T. Ces resultats mettent en evidence des alterations du compartiment lymphocytaire T associees a une signature humorale anormale chez les sujets exposes a la silice.

Introduction La necrose fibrinoide (NF) est une lesion fondamentale des glomerulonephrites associees aux ANCA (GN-ANCA). Sa signification chez les patients atteints de GN-ANCA est mal connue. Methodes L’objectif de cette etude etait de confronter la presence de NF avec les caracteristiques initiales et evolutives de patients atteints de GN-ANCA. Les donnees des patients provenaient d’un registre de vascularite a ANCA comprenant les caracteristiques de patients admis dans un hopital universitaire et trois hopitaux regionaux. Les informations relatives a la presentation initiale, aux donnees histologiques et aux resultats ont ete recueillis. Les patients presentant une glomerulonephrite pauci-immune au diagnostic ou lors d’une rechute de la vascularite entre le 01/01/2000 et le 01/01/2018 etaient inclus. Resultats obtenus ou attendus Parmi les 142 patients du registre, 116 remplissaient les criteres d’inclusion et ont ete analysees. La NF etait detectee dans 42,2 % des biopsies. Les patients avec NF presentaient un DFG plus bas, un besoin plus frequent d’epuration extra-renale et un taux moins eleve de rechute en comparaison des patients sans NF. La NF n’etait pas significativement associee a d’autres lesions glomerulaires. La survie sans rechute etait significativement plus importante chez les patients avec NF. L’analyse univariee retrouvait comme facteur de risque le phenotype de GPA, l’atteinte ORL, le taux plus bas de creatinine serique, et l’absence de NF. En analyse de Cox multivariee, l’absence de NF dans les GN-ANCA conferait un risque trois fois plus important de rechute apres ajustement sur les autres facteurs de risque. Conclusion Le statut « absence » ou « presence » de NF aux biopsies de patients avec GN-ANCA permet l’identification de deux sous-types de patients avec des risques de rechutes differents. Ce travail suggere que la NF pourrait etre un marqueur fiable d’evaluation du risque de rechute des vascularites a ANCA et qu’elle devrait etre evaluee dans des etudes prospectives ulterieures.

International audience; Background: Recent studies have demonstrated the key role of the complement alternative pathway (cAP) in the pathophysiology of experimental ANCA-associated vasculitis (AAV). However, in human AAV the role of cAP has not been extensively explored. In the present work, we analysed circulating serum C3 levels measured at AAV onset and their relation to outcomes.Methods: We conducted a retrospective observational cohort study including 45 consecutive patients with AAV diagnosed between 2000 and 2014 with serum C3 measurement at diagnosis, before immunosuppressive treatment initiation. Two groups were defined according to the median serum C3 level value: the low C3 group (C3

Introduction Les hemorragies obstetricales constituent une cause non negligeable d’insuffisance renale. Nous rapportons 2 nouveaux cas de necrose corticale compliquant une hemorragie du post-partum (HPP) et ayant justifie la prescription d’acide tranexamique (ATX). Observation Deux patientes (28 et 34 ans), primipares, ont presente une HPP (accouchement a 39 SA et 40 SA) traitee par poly-transfusion et ATX. Les suites immediates sont compliquees d’une IRA anurique avec tableau de HELLP syndrome. Les stigmates de microangiopathie thrombotique (MAT) se sont amendes en 72 heures. L’IRM renale montrait un defaut de rehaussement du cortex renal bilateral. Le recours a la dialyse chronique a ete necessaire avec un sevrage a 5 mois pour l’un des cas. Une declaration de pharmacovigilance a ete realisee. Discussion Ces deux patientes presentaient des facteurs de risque renal majeurs : HELLP syndrome, troubles de la coagulation associes, transfusion en quantite importante (CG et PFC) et administration d’un anti-fibrinolytique (ATX donne a des doses > 2 g). En cas d’endotheliopathie, l’ATX induirait une MAT renale severe. Une mise a jour du resume des caracteristiques du produit (RCP) de l’ATX est en cours depuis le rapport d’expertise du Comite Technique de Pharmacovigilance de decembre 2013. Conclusion En cas de fibrinolyse et d’hemolyse liee a une HPP, l’ATX administre dans ce contexte apparait comme un facteur d’aggravation du processus micro-thrombotique, avec un possible effet-dose (> 2 g). La mise en place d’un registre national de ces cas de necrose corticale du post-partum est a discuter.

Introduction L’insuffisance renale aigue (IRA) est une complication frequente et severe chez les patients d’oncohematologie. Son incidence y est plus elevee et son pronostic plus reserve. Si l’insuffisance renale est le plus souvent multifactorielle (sepsis, deshydratation, tubulotoxicite, micro-angiopathie…), certaines etiologies sont specifiques. Le methotrexate (MTX) peut induire une IRA par precipitation intratubulaire. Une mutation de la methylene tetrahydrofolate reductase (C677 T MTHFR) est responsable d’une toxicite accrue au MTX. Observation Une patiente de 39 ans aux antecedents de leucemie aigue myelocytaire de type 3 (LAM 3) sous chimiotherapie d’entretien par acide tout-transretinoique, 6-mercaptopurine et MTX est hospitalisee pour troubles digestifs. La biologie montre une pancytopenie, des stigmates d’hemolyse micro-angiopathique, une insuffisance hepato-cellulaire et une insuffisance renale aigue de profil tubulaire. A la BOM, la mœlle est desertique, sans blastes, pas d’hemophagocytose. L’activite de l’ADAMTS 13 est a 24 %, la recherche de clone HPN est negative et l’etude pharmacogenetique retrouve une mutation heterozygote C677 T du gene MTHFR sans deficit en thiopurine S-methyltransferase (TPMT). En l’absence d’amelioration une biopsie renale est realisee objectivant des lesions de micro-angiopathie thrombotique (MAT) a predominance glomerulaire associees a des lesions tubulaires aigues. La serologie Escherichia coli O157 :H7 revient positive. Discussion L’interpretation initiale a ete une toxicite systemique du MTX sur genotype predisposant. La PBR a permis de conclure a un SHU-D+ a E. coli O157 :H7. En raison d’une dialyse-dependance, 4 cures hebdomadaires d’ECULIZUMAB 600 mg ont ete realisees permettant une normalisation de la fonction renale. Conclusion L’IRA du patient d’oncohematologie est frequemment plurifactorielle avec un impact pronostique variable. La biopsie renale garde tout son interet sur ce terrain. En cas de toxicite severe chez un patient traite par MTX, une recherche de mutations du gene de la MTHFR doit etre effectuee.