Mycophenolate mofetil for steroid-dependent nephrotic syndrome: a phase II Bayesian trial
ABSTRACT Mycophenolate mofetil (MMF) has emerged as a new therapeutic option in steroid-dependent nephrotic syndrome (SDNS). We conducted a phase II Bayesian trial of MMF in children with SDNS. Phase II trials, usually single-arm studies, investigate the effect of new treatments. Standard Fleming's procedure relies on observed results (relapse rate during the trial), whereas Bayesian approach combines observed results with prior information (expected relapse rate according to prior studies and clinical experience). All patients were required to have received prior alkylating-agent treatment. Sixty-seven percent of them had also received levamisole. Patients received MMF (1,200 mg/m(2)/day) and prednisone according to a defined schedule [reduction of alternate-day (e.o.d) dose to 50% of pre-MMF dose at 3 months, 25% at 6 months]. Twenty-four children (median age 6.0 years, 2.8-14.4) entered the study and 23 completed it. Bayesian analysis showed that adding four patients would not change significance of results, allowing stopping inclusions. Four patients relapsed during the first 6 months (estimated probability 17.6%, 95% credibility interval: 5.4-35.0%) and two at months 8 and 11.5. In the 19 patients free of relapse during the first 6 months, median (Q1-Q3) prednisone maintenance dose decreased from 25 (10-44) to 9 (7.5-11.2) mg/m(2) e.o.d (p < 0.001) and cumulative dose from 459 (382-689) to 264 (196-306) mg/m(2)/month (p < 0.001) before and on MMF respectively. Pre-MMF patient characteristics and MMF pharmacokinetics did not differ between patients with or without relapse. MMF reduces relapse rate and steroid dose in children with SDNS and should be proposed before cyclosporine and cyclophosphamide.
Article: Nephrotic Syndrome: State of the Art[Show abstract] [Hide abstract]
ABSTRACT: This article overviews the pathogenesis and management of idiopathic nephrotic syndrome, a common childhood glomerulopathy. While initial evidence supported an imbalance of T helper responses in patients with nephrotic syndrome, recent studies suggest alterations in both innate and adaptive immune responses, including evidence for impaired T regulatory function. The central role of the podocyte in causing proteinuria is confirmed by the observation of mutations in key podocyte proteins in steroid-resistant nephrotic syndrome and experimental evidence of altered podocyte signaling and cytoskeletal organization, which might be corrected by medications. The outcome and management of idiopathic nephrotic syndrome in children are determined by the response to corticosteroids and the frequency of relapses. While patients with steroid-sensitive nephrotic syndrome have a favorable long-term outcome, almost half of them relapse frequently and are at risk of adverse effects of corticosteroids. Various non-corticosteroid immunosuppressive agents are used to prolong disease remission, but require careful monitoring for potential adverse effects. While calcineurin inhibitors are the choice of therapy for patients with steroid-resistant nephrotic syndrome, long-term management of disease is challenging due to variable response to immunosuppression, therapy-related adverse effects, and high rates of disease progression to end-stage renal disease. Information from recent randomized clinical trials has helped to clarify and improve the standard of care for childhood nephrotic syndrome and underscore the need for well-designed collaborative studies.12/2014; 3(1). DOI:10.1007/s40124-014-0066-4
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ABSTRACT: IntroductionNephrotic syndrome is a disorder characterized by severe proteinuria, hypoproteinemia, and generalized edema resulting from damage to the glomerular basement membrane. In Western countries, nephrotic syndrome affects 2 of 100,000 children per year . In Japan, approximately 1,300 new cases per year of pediatric nephrotic syndrome are reported to the Medical Aid for Specific Chronic Disease of Children and the disease develops in 5 of 100,000 children per year. Approximately 90 % of the cases of pediatric nephrotic syndrome are idiopathic, or of unknown cause. The first-line treatment for an initial episode of pediatric idiopathic nephrotic syndrome is oral steroid therapy, which leads to remission in approximately 80 % of cases (steroid-sensitive nephrotic syndrome) . However, 80 % of children with steroid-sensitive nephrotic syndrome experience one or more relapses,  and 50 % of these children have frequent relapses . Those with frequently relapsing nephrotic sy ...Clinical and Experimental Nephrology 02/2015; 19(1). DOI:10.1007/s10157-014-1030-x · 1.71 Impact Factor
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ABSTRACT: The KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for management of glomerulonephritis was recently released. The Canadian Society of Nephrology convened a working group to review the recommendations and comment on their relevancy and applicability to the Canadian context. A subgroup of pediatric nephrologists reviewed the guideline statements for management of childhood nephrotic syndrome and agreed with most of the guideline statements developed by KDIGO. This commentary highlights areas in which there is lack of evidence and areas in need of translation of evidence into clinical practice. Areas of controversy or uncertainty, including the length of corticosteroid therapy for the initial presentation and relapses, definitions of steroid resistance, and choice of second-line agents, are discussed in more detail. Existing practice variation is also addressed.American Journal of Kidney Diseases 01/2014; 63(3). DOI:10.1053/j.ajkd.2013.12.002 · 5.76 Impact Factor