TRAITEMENT DU PURPURA RHUMATOIDE (ETUDE RETROSPECTIVE ET REVUE DE LA LITTERATURE)

AMIENS-BU Santé (800212102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

BK Polyomavirus Micro-RNAs: Time Course and Clinical Relevance in Kidney Transplant Recipients

Background: Kidney transplant recipients (KTRs) are exposed to a high risk of BK polyomavirus (BKPyV) replication, which in turn may lead to graft loss. Although the microRNAs (miRNAs) bkv-miR-B1-3p and bkv-miR-B1-5p are produced during the viral cycle, their putative value as markers of viral replication has yet to be established. In KTRs, the clinical relevance of the changes over time in BKPyV miRNA levels has not been determined. Methods: In a retrospective study, we analyzed 186 urine samples and 120 plasma samples collected from 67 KTRs during the first year post-transplantation. Using a reproducible, standardized, quantitative RT-PCR assay, we measured the levels of bkv-miR-B1-3p and bkv-miR-B1-5p (relative to the BKPyV DNA load). Results: Detection of the two miRNAs had low diagnostic value for identifying patients with DNAemia or for predicting DNAuria during follow-up. Seven of the 14 KTRs with a sustained BKPyV infection within the first year post-transplantation showed a progressive reduction in the DNA load and then a rapid disappearance of the miRNAs. DNA and miRNA loads were stable in the other seven KTRs. Conclusions: After the DNA-based diagnosis of BKPyV infection in KTRs, bkv-miR-B1-3p and bkv-miR-B1-5p levels in the urine might be valuable markers for viral replication monitoring and thus might help physicians to avoid an excessive reduction in the immunosuppressive regimen

The impact of pre-graft serology on the risk of BKPyV infection post-renal transplantation

International audienceAbstract Objectives BK polyomavirus associated nephropathy, is a troublesome disease induced by BK polyomavirus (BKPyV) infection in immunocompromised renal graft recipients with no effective available treatment, making immunosuppression reduction the only management option. Thus, pre-graft predictive BKPyV replication markers are needed for high-risk viremia patient identification. Methods we conducted a retrospective study to assess the correlation between the BKPyV pre-transplant serostatus and post-transplant BKPyV infection incidence. Sera from 329 recipients and 222 matched donors were tested for anti-BKV antibodies against BKPyV serotypes I and IV by a VLPs-based IgG ELISA, and BKPyV DNA load was monitored for at least 1 year post transplantation. Results 80 recipients were viruric and 59 recipients were viremic post transplantation. In the post-transplant period, the probability of developing viremia for serotype I was increasing from 4.3% for the D-/R + group to 12.1% for the D+/R + group and climbing to 37.5% for the D+/R- group (p < 0.05). When calculating the recipient mean titers for serotypes I and IV, we observed a clear difference in the proportions of viremia passing from 50% for mean titers < 400 to 13.5% for titers ≥ 400 (p < 0.001) with also a higher proportion of presumptive nephropathy (50% vs 23.1%, p < 0.05). In univariate analysis this parameter has an odds ratio of 6.41 for the risk of developing post-transplant BKPyV viremia (95% CI: 3.16–13.07; p < 0.0001). Conclusions Both donor and recipient BKPyV seropositivity determination before transplantation and antibody titer may serve as a predictive tool to manage clinical BKPyV infection by identification of patients at high risk

Eculizumab in gemcitabine-induced thrombotic microangiopathy: experience of the French thrombotic microangiopathies reference centre

International audienceBackground: Gemcitabine is a broadly prescribed chemotherapy, the use of which can be limited by renal adverse events, including thrombotic microangiopathy (TMA). Methods: This study evaluated the efficacy of eculizumab, a monoclonal antibody targeting the terminal complement pathway, in patients with gemcitabine-induced TMA (G-TMA). We conducted an observational, retrospective, multicenter study in 5 French centres, between 2011 and 2016. Results: Twelve patients with a G-TMA treated by eculizumab were included. The main characteristics were acute renal failure (100%), including stage 3 acute kidney injury (AKI, 58%) and renal replacement therapy (17%), hypertension (92%) and diffuse oedema (83%). Eculizumab was started after a median of 15 days (range 4-44) following TMA diagnosis. A median of 4 injections of eculizumab was performed (range 2-22). Complete hematological remission was achieved in 10 patients (83%) and blood transfusion significantly decreased after only one injection of eculizumab (median of 3 packed red blood cells (range 0-10) before treatment vs 0 (range 0-1) after one injection, P < 0.001). Two patients recovered completely renal function (17%), and 8 achieved a partial remission (67%). Compared to a control group of G-TMA without use of eculizumab, renal outcome was more favourable. At the end of the follow up, median eGFR was 45 vs 33 ml/min/1.73m 2 respectively in the eculizumab group and in the control group. Conclusions: These results suggest that eculizumab is efficient on haemolysis and reduces transfusion requirement in G-TMA. Moreover, eculizumab may improve renal function recovery

Systemic autoimmune disorders associated with thrombotic microangiopathy: A cross-sectional analysis from the French National TMA registry: Systemic autoimmune disease-associated TMA

International audienceContext - The management of systemic auto-immune diseases (SAID) -associated thrombotic microangiopathies (TMA) [SAID-TMA] remains debated. Objectives - To provide a demographic, clinical and therapeutic picture of SAID-TMA. Methods - A cross-sectional analysis was conducted on adult patients presenting with SAID and TMA from the French National TMA Registry over a 20-year period. Clinical features were extracted and compared to those from a historical cohort of atypical haemolytic and uremic syndrome (aHUS) patients. Results - Forty-one patients with SAID-TMA were compared to 78 patients with aHUS from a historical cohort. Connective tissue diseases (CTD) were systemic lupus erythematosus (n=18), primary Sjögren's syndrome (n=7), systemic sclerosis (n=11), mixed CTD (n=2) and 2 cases of vasculitides, including 7 overlapping forms and 8 cases of primary antiphospholipid syndromes (APLS). Patients with SAID-TMA generally had pre-existing chronic kidney failure (OR= 3.17, 95%CI: 1.204 to 7.923; p= 0.016) compared to aHUS patients, though creatinine levels were significantly lower (216 [IQR, 108-334] µmol/L vs. 368 [IQR, 170-722] µmol/L; p= 0.002). Patients were less likely to recover if renal replacement therapy was needed at onset (OR= 0.07; 0.02 to 0.34; p 0.05). Conclusion - The management of SAID-TMA implies an early initiation of immunosuppressive drugs for flares of the associated SAID, whereas TPE seem ineffective. KEY MESSAGES

Mutations in INF2 Are a Major Cause of Autosomal Dominant Focal Segmental Glomerulosclerosis

The recent identification of mutations in the INF2 gene, which encodes a member of the formin family of actin-regulating proteins, in cases of familial FSGS supports the importance of an intact actin cytoskeleton in podocyte function. To determine better the prevalence of INF2 mutations in autosomal dominant FSGS, we screened 54 families (78 patients) and detected mutations in 17% of them. All mutations were missense variants localized to the N-terminal diaphanous inhibitory domain of the protein, a region that interacts with the C-terminal diaphanous autoregulatory domain, thereby competing for actin monomer binding and inhibiting depolymerization. Six of the seven distinct altered residues localized to an INF2 region that corresponded to a subdomain of the mDia1 diaphanous inhibitory domain reported to co-immunoprecipitate with IQ motif–containing GTPase-activating protein 1 (IQGAP1). In addition, we evaluated 84 sporadic cases but detected a mutation in only one patient. In conclusion, mutations in INF2 are a major cause of autosomal dominant FSGS. Because IQGAP1 interacts with crucial podocyte proteins such as nephrin and PLCε1, the identification of mutations that may alter the putative INF2–IQGAP1 interaction provides additional insight into the pathophysiologic mechanisms linking formin proteins to podocyte dysfunction and FSGS

Predictive features of chronic kidney disease in atypical haemolytic uremic syndrome

French Thrombotic Microangiopathies Reference CentreInternational audienceChronic kidney disease (CKD) is a frequent and serious complication of atypical haemolytic uremic syndrome (aHUS). We aimed to develop a simple accurate model to predict the risk of renal dysfunction in aHUS based on clinical and biological features available at hospital admission. Renal function at 1-year follow-up, based on an estimated glomerular filtration rate < 60mL/min/1.73m 2 as assessed by the Modification of Diet in Renal Disease equation, was used as an indicator of significant CKD. Prospectively collected data from a cohort of 156 aHUS patients who did not receive eculizumab were used to identify predictors of CKD. Covariates associated with renal impairment were identified by multivariate analysis. The model performance was assessed and a scoring system for clinical practice was constructed from the regression coefficient. Multivariate analyses identified three predictors of CKD: a high serum creatinine level, a high mean arterial pressure and a mildly decreased platelet count. The prognostic model had a good discriminative ability (area under the curve = .84). The scoring system ranged from 0 to 5, with corresponding risks of CKD ranging from 18% to 100%. This model accurately predicts development of 1-year CKD in patients with aHUS using clinical and biological features available on admission. After further validation , this model may assist in clinical decision making

Understanding the Health Literacy in Patients With Thrombotic Thrombocytopenic Purpura

Following an acute thrombotic thrombocytopenic purpura (TTP) episode, patients are at risk for relapse, and a careful long-term follow-up is needed. Adherence to the follow-up by patients implies a good understanding of the disease. However, TTP literacy in patients is currently unknown. To explore the TTP literacy in patients and identify factors associated with poor disease understanding, a questionnaire was developed focusing on patient's characteristics, knowledge about TTP and patients’ actions in an emergency. The questionnaire was presented to 120 TTP patients in remission from the French National Registry for Thrombotic Microangiopathies. TTP literacy was low in 24%, intermediate in 43% and high in 33% of the patients. Low TTP literacy was associated with older age and low education level. Among the knowledge gaps identified, few patients knew that plasma exchange in acute phase is mandatory and has to be done daily (39%), 47% of participants did not consider themselves at risk for relapse, and 30% of women did not know that pregnancy exposes them to a greater risk of relapse. Importantly, few patients responded about life-saving actions in an emergency. Hence, the design of educational material should pay special attention to the age and education level of the target population focusing on the events leading to TTP, the importance of the emergency treatment, controllable predisposing factors for TTP development and patient attitude in an emergency.status: publishe