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Background: Fabry disease (FD) is a rare X-linked lysosomal disorder caused by pathogenic variants in the alpha-galactosidase-A gene (GLA). Life threatening complications in adulthood include chronic kidney failure, strokes and the cardiac involvement which is the leading cause of mortality. Usually, it presents with hypertrophic cardiomyopathy, together with arrhythmia and conduction abnormalities. An early indicator is decreased T1 value on cardiac magnetic resonance (CMR). Enzyme replacement therapy (ERT) is effective on some extra-cardiac symptoms but its effect on cardiac lesions depends on the level of initial myocardial lesions. CMR is routinely used to monitor cardiac involvement in FD due to its capacity for tissular characterization. However, there is a lack of data on the pediatric population to understand how to integrate CMR into early therapeutic decisions. Method: Monocentric longitudinal study carried out at Montpellier University Hospital from 2016 to 2022. All pediatric patients with FD were evaluated over time with clinical, biological, and cardiac imaging (CMR, echocardiography). Results: Out of the six patients included, (3 males), five were treated with ERT during the study. Low T1 values were observed in 4 patients. The normalization of T1 values was observed after 4 years of ERT in 3 patients. Conclusion: Due to the lack of strong clinical and biological markers of FD in pediatric patients, initiation and follow-up of ERT efficacy remain challenging. CMR with T1-mapping, a noninvasive method, could play a role in the evaluation of early cardiac impairment in young patients at diagnosis and during follow-up with or without ERT.
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BACKGROUND AND OBJECTIVES: Therapeutic drug monitoring of mycophenolic acid can improve clinical outcome in organ transplantation and lupus, but data are scarce in idiopathic nephrotic syndrome. The aim of our study was to investigate whether mycophenolic acid pharmacokinetics are associated with disease control in children receiving mycophenolate mofetil for the treatment of steroid-dependent nephrotic syndrome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a retrospective multicenter study including 95 children with steroid-dependent nephrotic syndrome treated with mycophenolate mofetil with or without steroids. Area under the concentration-time curve of mycophenolic acid was determined in all children on the basis of sampling times at 20, 60, and 180 minutes postdose, using Bayesian estimation. The association between a threshold value of the area under the concentration-time curve of mycophenolic acid and the relapse rate was assessed using a negative binomial model. RESULTS: In total, 140 areas under the concentration-time curve of mycophenolic acid were analyzed. The findings indicate individual dose adaptation in 53 patients (38%) to achieve an area under the concentration-time curve target of 30-60 mg·h/L. In a multivariable negative binomial model including sex, age at disease onset, time to start of mycophenolate mofetil, previous immunomodulatory treatment, and concomitant prednisone dose, a level of area under the concentration-time curve of mycophenolic acid >45 mg·h/L was significantly associated with a lower relapse rate (rate ratio, 0.65; 95% confidence interval, 0.46 to 0.89; P=0.01). CONCLUSIONS: Therapeutic drug monitoring leading to individualized dosing may improve the efficacy of mycophenolate mofetil in steroid-dependent nephrotic syndrome. Additional prospective studies are warranted to determine the optimal target for area under the concentration-time curve of mycophenolic acid in this population.
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Fatores Imunológicos/farmacocinética , Fatores Imunológicos/uso terapêutico , Ácido Micofenólico/farmacocinética , Ácido Micofenólico/uso terapêutico , Síndrome Nefrótica/tratamento farmacológico , Área Sob a Curva , Pré-Escolar , Feminino , Glucocorticoides/uso terapêutico , Humanos , Fatores Imunológicos/sangue , Masculino , Ácido Micofenólico/sangue , Prednisona/uso terapêutico , Recidiva , Estudos RetrospectivosRESUMO
BACKGROUND: Rituximab (RTX) has recently showed promising results in the treatment of steroid-dependent idiopathic nephrotic syndrome (SDNS). METHODS: This was a retrospective multicenter study of 18 children treated with RTX for SDNS, with a mean follow-up of 3.2 years. RTX was introduced because of side effects or relapses during therapy with immunosuppressive agents. The children received one to four infusions of RTX during the first course of treatment, and subsequent infusions were given due to CD19-cell recovery (CD19 >1 %; 54 % of children) or relapse (41 %), as well as systematically (5 %). RESULTS: Treatment with RTX maintained sustained remission without relapse in 22 % of patients and increased the duration of remission in all other patients. The time between two successive relapses was 9 months in the absence of re-treatment and 24.5 months when infusions were performed at the time of CD19-cell recovery. At the last follow-up, 44.5 % of patients were free of oral drug therapy. Of those still receiving oral drugs, all doses had been decreased. No serious adverse events occurred. CONCLUSION: The results of this retrospective study confirm the efficacy and very good safety of RTX in the treatment of SDNS. The optimal therapeutic protocol seems to be a repeated single infusion at the time of CD19-cell recovery.
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Anticorpos Monoclonais Murinos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Síndrome Nefrótica/tratamento farmacológico , Anticorpos Monoclonais Murinos/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Rituximab , Fatores de Tempo , Resultado do TratamentoRESUMO
Mycoplasma pneumoniae-associated nephritis has been reported in children with various pathological findings. It nevertheless remains an uncommon disease and, within this clinical context, endo-and extracapillary glomerulonephritis in a child has never been described. We report here a case of a 3-year-old girl diagnosed with severe crescentic glomerulonephritis associated with M. pneumoniae infection who presented with nephrotic syndrome and impaired renal function. The serum C3 complement level was initially low but returned to normal after 1 month. Two courses of three methylprednisolone pulses were administered in association with plasmapheresis and, secondarily, mycophenolate mophetil. This treatment regimen led to disease remission and a favorable renal outcome at the 6-month follow-up. However, the treatment guidelines in this situation remain debatable.