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      Steroid-sensitive nephrotic syndrome in children: triggers of relapse and evolving hypotheses on pathogenesis

      Italian Journal of Pediatrics

      BioMed Central

      Relapse, Steroid-sensitive nephrotic syndrome, Children, Pathogenesis

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          Abstract

          Nephrotic syndrome remains the most common manifestation of glomerular disease in childhood. Minimal change nephropathy is the most common cause of the syndrome in children. Despite its initial high response rate to corticosteroids and its favorable prognosis, relapses are common leading to increased morbidity and cost of treatment.

          This review seeks to appraise the common triggers of relapse and to highlight the evolving hypotheses about the pathogenesis of the syndrome. Literature search was conducted through PubMed, Google web search and Cochrane Database of Systematic reviews using relevant search terms.

          Acute respiratory infections and urinary tract infections are the most frequent infectious triggers of relapse. Targeted interventions like initiating corticosteroid or its dose-adjustment during episodes of acute respiratory infection and zinc supplementation are reportedly effective in reducing relapse rates. Hypotheses on pathogenesis of the syndrome have evolved from the concepts of ‘immune dysregulation’, ‘increased glomerular permeability’ to ‘podocytopathy’.

          Although development of drugs which can regulate the pathways for podocyte injury offers future hope for effective and targeted treatment, the relapse-specific interventions currently contribute to significant reduction in disease morbidity.

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          Most cited references 53

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          Nephrotic syndrome in children: prediction of histopathology from clinical and laboratory characteristics at time of diagnosis. A report of the International Study of Kidney Disease in Children.

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            Role of zinc administration in prevention of childhood diarrhea and respiratory illnesses: a meta-analysis.

            The quantified effect of zinc supplementation to prevent childhood diarrhea and respiratory illnesses is unclear. We conducted a meta-analysis of randomized, controlled trials on the subject. We searched PubMed, Science Citation Index, and the Cochrane Database of Controlled Trials and hand-searched the reference lists of identified articles. All randomized, controlled trials of zinc supplementation for > or = 3 months for children < 5 years of age, using blinded assessment, were eligible. The outcome measures studied were number of episodes of illness, number of days with illness, and number of episodes of severe illness. Data from 17 studies were pooled by using random-effects and fixed-effects models for data with and without significant heterogeneity, respectively. Children who received a zinc supplement had fewer episodes of diarrhea (rate ratio: 0.86) and respiratory tract infections (rate ratio: 0.92) and significantly fewer attacks of severe diarrhea or dysentery (rate ratio: 0.85), persistent diarrhea (rate ratio: 0.75), and lower respiratory tract infection or pneumonia (rate ratio: 0.80) than did those who received placebo. They also had significantly fewer total days with diarrhea (rate ratio: 0.86) but not days with respiratory illness (rate ratio: 0.95). Published studies showed a publication bias and significant heterogeneity; however, no cause for the latter could be identified. Zinc supplementation reduced significantly the frequency and severity of diarrhea and respiratory illnesses and the duration of diarrheal morbidity. The relatively limited reduction in morbidity and the presence of significant heterogeneity and of publication bias indicate the need for larger, high-quality studies to identify subpopulations most likely to benefit.
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              Rituximab for idiopathic membranous nephropathy.

              Treatments for idiopathic membranous nephropathy, a common cause of nephrotic syndrome, can be very toxic. In view of the pathogenic potential of B cells in this disease, we studied the effects of four weekly infusions of rituximab (375 mg/m(2)-- the monoclonal antibody to B-cell antigen CD20--in eight patients who had idiopathic membranous nephropathy with persistent nephrotic syndrome. At weeks 4 and 20, urinary protein decreased from mean (SE) 8.6 g/24 h (1.4) to 3.8 (0.8) and 3.7 (0.9), respectively (p<0.0001). At week 20, albuminuria and albumin fractional clearance decreased by 70% and 65%, and serum albumin increased by 31%. CD20 B lymphocytes fell below normal ranges up to study end. The short-term risk-benefit profile of rituximab seems more favourable to that of any other immunosuppressive drug used to treat idiopathic membranous nephropathy.
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                Author and article information

                Contributors
                snuwaezuoke@yahoo.com
                Journal
                Ital J Pediatr
                Ital J Pediatr
                Italian Journal of Pediatrics
                BioMed Central (London )
                1824-7288
                21 March 2015
                21 March 2015
                2015
                : 41
                Affiliations
                Department of Paediatric Nephrology Unit, University of Nigeria Teaching Hospital, Postal code- 400001 Ituku-Ozalla, Enugu, Enugu State Nigeria
                Article
                123
                10.1186/s13052-015-0123-9
                4379699
                © Uwaezuoke; licensee BioMed Central. 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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                Review
                Custom metadata
                © The Author(s) 2015

                Pediatrics

                pathogenesis, children, steroid-sensitive nephrotic syndrome, relapse

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