BMJ Open

Introduction Guidelines for the treatment of steroid-dependent nephrotic syndrome (SDNS) and frequently relapsing nephrotic syndrome (FRNS) are lacking. Given the substantial impact of SDNS/FRNS on quality of life, strategies aiming to provide long-term remission while minimising treatment side effects are needed. Several studies confirm that rituximab is effective in preventing early relapses in SDNS/FRNS; however, the long-term relapse rate remains high (~70% at 2 years). This trial will assess the association of intravenous immunoglobulins (IVIgs) to rituximab in patients with SDNS/FRNS and inform clinicians on whether IVIg’s immunomodulatory properties can alter the course of the disease and reduce the use of immunosuppressive drugs and their side effects. Methods and analysis We conduct an open-label multicentre, randomised, parallel group in a 1:1 ratio, controlled, superiority trial to assess the safety and efficacy of a single infusion of rituximab followed by IVIg compared with rituximab alone in childhood-onset FRNS/SDNS. The primary outcome is the occurrence of first relapse within 24 months. Patients are allocated to receive either rituximab alone (375 mg/m²) or rituximab followed by IVIg, which includes an initial Ig dose of 2 g/kg, followed by 1.5 g/kg injections once a month for the following 5 months (maximum dose: 100 g). Ethics and dissemination The study has been approved by the ethics committee (Comité de Protection des Personnes) of Ouest I and authorised by the French drug regulatory agency (Agence Nationale de Sécurité du Médicament et des Produits de Santé). Results of the primary study and the secondary aims will be disseminated through peer-reviewed publications

Guidelines for diagnosis and management of the cobalamin-related remethylation disorders cblC, cblD, cblE, cblF, cblG, cblJ and MTHFR deficiency

BACKGROUND: Remethylation defects are rare inherited disorders in which impaired remethylation of homocysteine to methionine leads to accumulation of homocysteine and perturbation of numerous methylation reactions. OBJECTIVE: To summarise clinical and biochemical characteristics of these severe disorders and to provide guidelines on diagnosis and management. DATA SOURCES: Review, evaluation and discussion of the medical literature (Medline, Cochrane databases) by a panel of experts on these rare diseases following the GRADE approach. KEY RECOMMENDATIONS: We strongly recommend measuring plasma total homocysteine in any patient presenting with the combination of neurological and/or visual and/or haematological symptoms, subacute spinal cord degeneration, atypical haemolytic uraemic syndrome or unexplained vascular thrombosis. We strongly recommend to initiate treatment with parenteral hydroxocobalamin without delay in any suspected remethylation disorder; it significantly improves survival and incidence of severe complications. We strongly recommend betaine treatment in individuals with MTHFR deficiency; it improves the outcome and prevents disease when given early

Variability of diagnostic criteria and treatment of idiopathic nephrotic syndrome across European countries

The aim of the surveys conducted by the Idiopathic Nephrotic Syndrome Working Group of the ESPN was to study the possible variability of treatment in Europe at different stages of the disease by means of questionnaires sent to members of the Working Group. Four surveys have been completed: treatment of the first flare, treatment of the first relapse and the issue of steroid dependency, use of rituximab, and the management of steroid-resistant patients. A uniform treatment of the first flare was applied in only three countries, and ten additional centers have adopted one of the three main protocols. Reported treatment of the first relapse was relatively uniform, whereas the use of additional immunosuppressants in steroid dependency was widely variable. Rituximab had already been used in hundreds of patients, although the formal evidence of efficiency in steroid dependency was relatively recent at the time of the survey. The definition of steroid resistance was variable in the European centers, but strikingly, the first-line treatment was uniform throughout the centers and included the combination of prednisone plus calcineurin antagonists. Conclusion: The variability in the approach of idiopathic nephrotic syndrome is unexpectedly large and affects treatment of the first flare, strategies in the case of steroid dependency, as well as the definitions of steroid resistance.What is Known:• Steroids and immunosuppressants are the universal treatment of idiopathic nephrotic syndrome.What is New:• The variability of treatments and strategy of treatment in European centers of pediatric nephrology

Successful anti-TNFalpha treatment in a child with posttransplant recurrent focal segmental glomerulosclerosis.

International audiencePosttransplant recurrence of focal and segmental glomulosclerosis (FSGS) occurs in approximately 30% of patients, and remains after uncontrolled despite increased immunosuppression and plasma exchanges (PE) in approximately 30% of cases. New immunosuppressive drugs might then be warranted. We report the case of a 15-year-old boy with FSGS leading to end-stage renal disease (ESRD) who presented with an early posttransplant recurrence of disease. Reinforced immunosuppression and PE resulted in partial and transient disease control, but proteinuria significantly decreased with anti-TNFalpha treatment (infliximab then etanercep). This is the first case report of successful anti-TNFalpha treatment despite a constant high activity of FSGS, as demonstrated by relapse after discontinuation of anti-TNFalpha agents

Efficacy of intralesional sodium thiosulfate injections for disabling tumoral calcinosis: Two cases

International audienceINTRODUCTION:Tumoral calcinosis (TC) is a difficult-to-treat complication that can occur during several diseases such as dermatomyositis or genetic hyperphosphatemia. It is a painful and disabling condition that can lead to local complications including joint mobility reduction, cutaneous ulceration and superinfection. For the largest lesions, the treatment relies essentially on surgery. Intravenous sodium thiosulfate (STS) is efficient to treat calciphylaxis in patients undergoing hemodialysis. Local injections of STS seem efficient in superficial calcifications.OBJECTIVE:To report the efficacy and safety of intra-lesional injections of STS in tumoral calcinosis.RESULTS:We report two cases of successful intra-lesional injections of STS. A 44-year-old woman, with a history of dermatomyositis, presenting large subcutaneous calcifications in the right elbow, and a 42-year-old man, with a history of familial tumoral calcinosis, presenting large intramuscular calcifications in the right buttock, received weekly intra-lesional of 1-3g STS injections for 12 and 21 months, respectively. In both cases, the treatment relieved pain and greatly reduced the tumoral calcinosis with a very significant functional improvement without specific adverse effects. In case 1, TC size decreased from 28.7*56.0mm at baseline to 21.5*30.6mm at M12 treatment (59% reduction). In case 2, TC reduced from 167.5*204.3mm at baseline to 86.2*85.2mm at M21 treatment (79% reduction).CONCLUSION:Local injection of STS could be a promising therapeutic strategy for large and deep TC lesions and could therefore be an alternative to surgery

[Parapneumonic pleural effusion incidence in a French region before and during the antipneumococcal vaccine era].

International audienceBACKGROUND AND AIMS: The aim of the study was to compare the incidence of parapneumonic pleural effusion in the Limousin region of France, based on the comparison of pre- and postvaccination periods. METHODS: Subjects, 0-18-years-old, were retrospectively identified by searching in computerized databases of coded discharge diagnosis for patients with a diagnosis of pleural effusion and/or empyema and/or pulmonary infection in all the pediatric departments in Limousin hospitals. Medical records were reviewed by one of the authors and those with parapneumonic effusion and confirmed or suspected pneumococcal infection were included in the study. Data from the children hospitalized for parapneumonic pleural effusion were collected for two periods: period A, from July 2000 to July 2006, and period B, from July 2006 to July 2009 (before and after the generalization of the antipneumococcal vaccination). The main endpoint was the number of parapneumonic pleural effusion cases in each period in order to calculate the incidence within each period. RESULTS: A total of 35 children were included: nine during period A and 26 during period B. The incidence was 1 per 100,000 children for period A and 5.8 per 100,000 for period B. Bacteriological tests allowed us to serotype eight S. pneumoniae over the two periods. All serotypes were non-vaccine serotypes (1, 3, and 19A). CONCLUSION: This study demonstrates the increase in parapneumonic pleural effusion in the Limousin region