Database: Ovid MEDLINE(R) <2006 to March Week 3 2010> Search Strategy: -------------------------------------------------------------------------------1 *nephrotic syndrome/ (812) 2 limit 1 to (english language and "all child (0 to 18 years)") (400) 3 limit 2 to "review articles" (30) 4 from 3 keep 1-30 (30) *************************** <1> Unique Identifier 19410518 Status MEDLINE Authors Bruneau S. Dantal J. Authors Full Name Bruneau, Sarah. Dantal, Jacques. Institution INSERM, U643, Nantes, F44093, France. Title New insights into the pathophysiology of idiopathic nephrotic syndrome. [Review] [80 refs] Source Clinical Immunology. 133(1):13-21, 2009 Oct. Abstract Corticoresistant idiopathic nephrotic syndrome (INS) is a glomerulopathy of unknown etiology whose original aspect is its recurrence after kidney transplantation in 30 to 50% of patients with end-stage renal disease. This suggests the involvement of circulating factors that would alter the glomerular filtration barrier, but whose nature remains elusive. Although a T cell immune origin has been suggested, the actual role of these cells in INS recurrence is still unclear. Here we present an 8-year-old patient with corticoresistant INS who developed a recurrence of her initial disease after kidney transplantation. Rituximab therapy was proposed 11 months after transplantation; although no immediate effect was induced, a slow but persistent decrease in proteinuria began a few months after Rituximab infusions despite cessation of plasma exchanges and steroid therapy. The pathophysiology of INS and the putative mechanisms of action of Rituximab are discussed. [References: 80] Publication Type Case Reports. Journal Article. Research Support, Non-U.S. Gov't. Review. <2> Unique Identifier 19169768 Status MEDLINE Authors Khaira A. Upadhyay BK. Sharma A. Das P. Mahajan S. Makhariya G. Dinda AK. Agarwal SK. Tiwari SC. Authors Full Name Khaira, Ambar. Upadhyay, Bala Krishna. Sharma, Alok. Das, Prasenjit. Mahajan, Sandeep. Makhariya, Govind. Dinda, Amit K. Agarwal, Sanjay K. Tiwari, Suresh C. Institution Department of Nephrology, All India Institute of Medical Sciences, New Delhi, India. Title Hepatitis B virus associated focal and segmental glomerular sclerosis: report of two cases and review of literature. [Review] [17 refs] Source Clinical & Experimental Nephrology. 13(4):373-7, 2009 Aug. Abstract The hepatitis B virus (HBV) is estimated to have infected about 350 million people worldwide, making it one of the most common human pathogens. Renal involvement is among its most common extra hepatic manifestations and usually manifests in the form of immune complex mediated glomerulopathy, such as membranous glomerulonephritis (MGN), membranoproliferative glomerulonephritis (MPGN), mesangioproliferative glomerulonephritis and immunoglobulin A (IgA) nephropathy. Occurrence of focal and segmental glomerular sclerosis (FSGS) with HBV infection is rare and only five cases have been reported earlier. We report two cases of hepatitis B associated FSGS. In both the cases, HBsAg was demonstrated in the renal tissue and both the cases showed response to treatment with lamivudine, thus indicating a possible causal association between the viral infection and occurrence of nephrotic syndrome. [References: 17] Publication Type Case Reports. Journal Article. Review. <3> Unique Identifier 19615560 Status MEDLINE Authors Lane JC. Kaskel FJ. Authors Full Name Lane, Jerome C. Kaskel, Frederick J. Institution Division of Kidney Diseases, Department of Pediatrics, Children's Memorial Hospital, 2300 Children's Plaza, Chicago, IL 60614, USA. email@example.com Title Pediatric nephrotic syndrome: from the simple to the complex. [Review] [40 refs] Source Seminars in Nephrology. 29(4):389-98, 2009 Jul. Abstract Remarkable advances have been made in the past decade in understanding the pathophysiology of idiopathic nephrotic syndrome. Although the initiating events leading to the onset of proteinuria still are not well defined, it has become increasingly clear that many glomerular diseases can be classified as podocytopathies, with injury to the podocyte playing a major role in the development and progression of disease. A complex interaction of immune system mediators, slit diaphragm signal transduction, podocyte injury and conformational change, and mediators of apoptosis and fibrosis determine the extent and nature of proteinuria and progression of glomerulosclerosis. New insights into the pathogenesis of idiopathic nephrotic syndrome likely will lead to innovative therapies and new approaches to management and prevention. [References: 40] Publication Type Journal Article. Review. <4> Unique Identifier 19606070 Status MEDLINE Authors Bramham K. Hunt BJ. Goldsmith D. Authors Full Name Bramham, Kate. Hunt, Beverley J. Goldsmith, David. Institution Biomedical Research Centre, Guy's and St Thomas' Foundation Hospitals, London SE1 9RT, United Kingdom. Title Thrombophilia of nephrotic syndrome in adults. [Review] [72 refs] Source Clinical Advances in Hematology & Oncology. 7(6):368-72, 2009 Jun. Publication Type Journal Article. Review. <5> Unique Identifier 19495800 Status MEDLINE Authors Haffner D. Fischer DC. Authors Full Name Haffner, Dieter. Fischer, Dagmar-Christiane. Title Nephrotic syndrome and rituximab: facts and perspectives. [Review] [25 refs] Source Pediatric Nephrology. 24(8):1433-8, 2009 Aug. Abstract Idiopathic nephrotic syndrome is the most frequent glomerular disease that presents during childhood and is mainly due to minimal change nephropathy (MCNS) and focal-segmental glomerulosclerosis (FSGS). Its treatment is still challenging, with up to 50% of the patients who are initially steroid sensitive (usually MCNS) being frequent relapsers and requiring additional long-term immunosuppression. However, current immunosuppressive regimens are associated with severe toxicity. Only half of the steroid-resistant patients (usually FSGS) achieve long-term remission even with intensive immunosuppression and plasma exchange. Rituximab (RTX), a chimeric monoclonal antibody inhibiting CD20-mediated B-cell proliferation and differentiation, has recently gained attention as a potentially successful therapy for complicated idiopathic nephrotic syndrome in children. A number of case reports and one prospective non-controlled multicenter trial point to the beneficial effects of RTX as a rescue therapy in children with steroid/cyclosporine-dependent or -resistant nephrotic syndrome. However, publication bias often results in positive outcomes being more likely to be reported than negative ones and, in particular, the safety profile of this drug in this group of patients remains unclear. Therefore, controlled randomized studies are required to assess this issue, to develop treatment guidelines, to evaluate the therapeutic and economical efficacy, and to define criteria for the selection of patients. [References: 25] Publication Type Editorial. Review. <6> Unique Identifier 19052471 Status MEDLINE Authors Wang DY. Mao JH. Zhang Y. Gu WZ. Zhao SA. Chen YF. Liu AM. Authors Full Name Wang, D Y. Mao, J H. Zhang, Y. Gu, W Z. Zhao, S A. Chen, Y F. Liu, A M. Institution The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, China. Title Kimura disease: a case report and review of the Chinese literature. [Review] [26 refs] Source Nephron. 111(1):c55-61, 2009. Abstract BACKGROUND: Kimura disease, often accompanied by nephrotic syndrome, is a rare, chronic inflammatory disorder of unknown cause. In this report, the clinical and histopathological characteristics of 20 Chinese patients with Kimura disease-associated nephrotic syndrome were retrospectively evaluated. METHODS: We report a case of Kimura disease that was diagnosed recently in our ward, with steroid-responsive but recurrent minimal-change nephrotic syndrome. Meanwhile, we also used three powerful Chinese journal search engines (Cqvip.com, Wanfang.data and ScienceChina) to search the cases reported in Chinese from 1984 to 2007. RESULTS: The nephrotic syndrome of our patient occurred 20 months after the onset of Kimura disease. Renal biopsy revealed minimal-change lesions. The patient was responsive to the steroid, but proteinuria recurred. In most of the 19 other cases, the onset of nephrotic syndrome occurred after subcutaneous masses. Renal biopsy in 13 cases showed mesangial proliferative glomerulonephritis in 9, minimal change disease in 2 and membrane nephropathy in 2 cases. Serum creatinine levels were elevated in 5 patients. CONCLUSION: Normally, Kimura diseaseassociated nephrotic syndrome patients are sensitive to prednisone therapy but are likely to relapse. In patients with recurrent nephrotic syndrome, renal insufficiency is not uncommon. Copyright 2008 S. Karger AG, Basel. [References: 26] Publication Type Case Reports. Journal Article. Research Support, Non-U.S. Gov't. Review. <7> Unique Identifier 19158142 Status MEDLINE Authors Hasan F. Authors Full Name Hasan, Fyeza. Institution Molecular Haematology and Cancer Biology Unit, Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK. firstname.lastname@example.org Title Towards evidence based medicine for paediatricians. Does daily prednisolone reduce the risk of relapse secondary to viral infections in steroid-dependent nephrotic syndrome?. [Review] [4 refs] Source Archives of Disease in Childhood. 94(2):168-9, 2009 Feb. Publication Type Journal Article. Review. <8> Unique Identifier 18937561 Status MEDLINE Authors Traum AZ. Authors Full Name Traum, Avram Z. Institution Harvard Medical School, Boston, MA, USA. email@example.com Title Urine proteomic profiling to identify biomarkers of steroid resistance in pediatric nephrotic syndrome. [Review] [29 refs] Source Expert Review of Proteomics. 5(5):715-9, 2008 Oct. Abstract Long-term prognosis for children with nephrotic syndrome (NS) is directly related to steroid responsiveness. There are currently no diagnostic tests that accurately predict steroid responsiveness in pediatric NS. The initial prolonged course of daily, high-dose corticosteroid therapy thus serves both as a diagnostic and therapeutic maneuver. Urine proteomics is emerging as a potentially rich source of noninvasive biomarkers of drug responsiveness in NS. In this article, we discuss some of the initial studies of the urinary proteome in NS as well as ongoing and future challenges, define the normal urinary proteome and address the overwhelming abundance of urinary albumin and its impact on biomarker discovery. [References: 29] Publication Type Journal Article. Research Support, Non-U.S. Gov't. Review. <9> Unique Identifier 18462046 Status MEDLINE Authors Liapis H. Authors Full Name Liapis, Helen. Institution Department of Pathology & Immunology, Washington University School of Medicine, St Louis, MO 63110, USA. firstname.lastname@example.org Title Molecular pathology of nephrotic syndrome in childhood: a contemporary approach to diagnosis. [Review] [55 refs] Source Pediatric & Developmental Pathology. 11(4):154-63, 2008 Jul-Aug. Abstract Molecular and genetic studies in the last 2 decades have shed new light on the understanding of congenital and infantile nephrotic syndrome (NS). Glomerular pathology may appear as minimal change disease, focal segmental glomerulosclerosis, or diffuse mesangial sclerosis, glomerular diseases now recognized as podocyte injuries and in part caused by altered podocyte genes. Even though genetic mutations are not implicated in all infants with NS, the study of familial disease and congenital NS reveals that proteinuria is in many patients due to specific gene mutations. The most common mutations are in 4 genes, 3 of which are podocyte genes: NPHS1 (Finnish nephropathy), NPHS2 (podocin-induced focal segmental glomerulosclerosis), WT1 (diffuse mesangial sclerosis), and LAMB2 (Pierson syndrome). Furthermore, these studies have improved our understanding of steroid-resistant NS in older children, particularly girls, in whom proteinuria may be due to WT1 mutations. Availability of molecular genetic testing and antibodies to specific gene products are closing the gap between histopathology of pediatric glomerular disease and molecular genetic diagnosis. Recognition of NS variants, which may be reversible (eg, mitochondrial mutations, viral disease), is important. This review discusses the most common entities and the differential diagnosis of pediatric NS from the pathologist's point of view, with an emphasis on congenital (<3 months) and infantile (3 months to 1 year) NS in light of molecular and genetic studies. [References: 55] Publication Type Journal Article. Review. <10> Unique Identifier 18425948 Status MEDLINE Authors Yuan W. Wang J. Wu T. Authors Full Name Yuan, W. Wang, J. Wu, T. Title Chinese herbal medicine Huangqi type formulations for nephrotic syndrome. [Review] [202 refs] Source Cochrane Database of Systematic Reviews. (2):CD006335, 2008. Abstract BACKGROUND: At present, there is a lack of safe and effective drugs for nephrotic syndrome (NS). Huangqi type formulations have been used to treat nephrotic syndrome for years in China, however the effects and safety of these formulations have not been systematically reviewed. OBJECTIVES: To assess the benefits and harms of Huangqi and Huangqi type formulations in treating NS in any age group, either as sole agents or in addition to other drug therapies. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Chinese Biomedicine Database (CBM), CNKI, VIP and reference lists of articles. There was no language restriction. Date of most recent search: June 2006. SELECTION CRITERIA: All randomised controlled trials (RCTs) assessing the use of Huangqi or Huangqi type formulations in treating NS in adults and children, either as sole agents or in addition to other drug therapies. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study quality and extracted data. For dichotomous outcomes (remission, side effects and Inefficacy rate), results were expressed as relative risk (RR) and 95% confidence intervals (CI). Continuous outcomes (triglycerides cholesterol, plasma albumin) results were expressed as mean difference (WMD) with 95% CI. MAIN RESULTS: Three studies were identified (n = 128), all comparing Huangqi type formulations with placebo. Huangqi injection had a positive effect on plasma albumin (WMD 6.90, 95% Cl 3.60 to 10.20) and cholesterol (WMD 2.13, 95% Cl -2.97 to -1.29). Huangqi and red Chinese date reduced some adverse reactions (Cushing's syndrome: RR 0.55, 95% Cl 0.32 to 0.94; hormone reduced syndrome: RR 0.58, 95% Cl 0.39 to 0.85, respiratory tract infection: RR 0.27, 95% Cl 0.08 to 0.88), but no benefit on reducing relapse. Huangqi and Danggui had a positive effect on cholesterol (WMD -0.85, 95% Cl -1.70 to 0.00). AUTHORS' CONCLUSIONS: Huangqi type formulations may have some positive effects in treating NS by increasing plasma albumin and reducing blood cholesterol, Cushing's syndrome, hormone reduced syndrome and respiratory tract infection. However, limited by the lack of high quality clinical studies, we are unable to recommend Huangqi type formulations for NS. Large, properly randomised, placebo-controlled, double-blind studies are required. [References: 202] Publication Type Journal Article. Meta-Analysis. Review. <11> Unique Identifier 18401158 Status MEDLINE Authors Candiano G. Musante L. Petretto A. Bruschi M. Santucci L. Urbani A. Scolari F. Gusmano R. Carraro M. Zennaro C. Vincenti F. Ghiggeri GM. Authors Full Name Candiano, Giovanni. Musante, Luca. Petretto, Andrea. Bruschi, Maurizio. Santucci, Laura. Urbani, Andrea. Scolari, Francesco. Gusmano, Rosanna. Carraro, Michele. Zennaro, Cristina. Vincenti, Flavio. Ghiggeri, Gian Marco. Institution Laboratory on Pathophysiology of Uremia, G. Gaslini Children Hospital, Genoa, Italy. Title Proteomics of plasma and urine in primary nephrotic syndrome in children. [Review] [61 refs] Source Contributions to Nephrology. 160:17-28, 2008. Abstract Primary nephrotic syndrome in children, especially the variant with segmental glomerulosclerosis, remains an unsolved clinical problem. In spite of some progress, its pathogenesis is still unknown and the therapy options are confined to gross immune modulation. Indirect evidence based on posttransplant recurrence of the disease suggested an implication of plasma factors, whose characterization remains in course. Besides historical candidates, research is now considering glyco- and lipoderivatives. Structural analysis of plasma and urinary proteins based on proteomics has recently shown an increased proteolysis of major components such as albumin and the implication of alpha 1-antitrypsin that represents the first-line defense against exogenous and endogenous substances with proteolytic activity. Albumin has also emerged as a major plasma antioxidant, and recent studies have demonstrated that in patients with active focal segmental glomerulosclerosis albumin undergoes massive and stable oxidation with sulfonation of Cys34, formation of an adduct with +48 Da molecular weight, changes of the net charge due to additional negative residues, and loss of free thiol group (SH) titration. Altogether, these data suggest that oxidative stress determines selective protein damages in focal segmental glomerulosclerosis patients with formation of new adducts and fragmentation of plasma proteins. Research should now address whether oxidation of podocyte proteins is important for the maintenance of renal selectivity and is involved in proteinuria. [References: 61] Publication Type Journal Article. Research Support, Non-U.S. Gov't. Review. <12> Unique Identifier 18332710 Status MEDLINE Authors Del Rio M. Kaskel F. Authors Full Name Del Rio, Marcela. Kaskel, Frederick. Institution Division of Pediatric Nephrology, Children's Hospital at Montefiore, Bronx, New York 10467, USA. email@example.com Title Evaluation and management of steroid-unresponsive nephrotic syndrome. [Review] [59 refs] Source Current Opinion in Pediatrics. 20(2):151-6, 2008 Apr. Abstract PURPOSE OF REVIEW: Idiopathic nephrotic syndrome in children is commonly associated with minimal change disease and response to steroid therapy. Steroid-unresponsive nephrotic syndrome is often characterized by persistent proteinuria and progression to chronic kidney disease. Focal segmental glomerulosclerosis is the leading cause of steroid-unresponsive nephrotic syndrome in childhood. There is no uniformed consensus as to the treatment of steroidunresponsive nephrotic syndrome. Advances in the pathogenesis, genetics and biomarkers or surrogate markers may be useful for the diagnosis and identification of patients with steroidunresponsive nephrotic syndrome, severity of disease, progression and response to therapy. RECENT FINDINGS: This review is intended to describe some of the recent changes in the epidemiology of steroid-unresponsive nephrotic syndrome, in particular focal segmental glomerulosclerosis, its pathogenesis and alternative therapies. SUMMARY: Recent studies in both children and adults have shown an increase in the incidence of focal segmental sclerosis as a cause of steroid-unresponsive nephrotic syndrome. Advances in the pathogenesis and noninvasive methods of diagnosis may allow for the identification of steroid-responsive patients. [References: 59] Publication Type Journal Article. Research Support, N.I.H., Extramural. Review. <13> Unique Identifier 18332709 Status MEDLINE Authors Hodson EM. Alexander SI. Authors Full Name Hodson, Elisabeth M. Alexander, Stephen I. Institution Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, NSW, Australia. Elisah@chw.edu.au Title Evaluation and management of steroid-sensitive nephrotic syndrome. [Review] [56 refs] Source Current Opinion in Pediatrics. 20(2):145-50, 2008 Apr. Abstract PURPOSE OF REVIEW: This review examines new literature published in 2006 and 2007 on steroid-sensitive nephrotic syndrome. RECENT FINDINGS: Steroid-sensitive nephrotic syndrome has long been thought to be due to lymphocyte-derived circulating factors leading to podocyte injury with subsequent proteinuria. New studies support this mechanism and implicate the T helper 2 cytokine IL-13. In addition a genetic mutation in familial nephrotic syndrome has been reported in a child, who responded to corticosteroid therapy. There are new clinical trial data supporting the efficacy of levamisole in steroid-sensitive nephrotic syndrome and preliminary trial data on mycophenolate mofetil supporting its efficacy as a steroid-sparing agent. Case reports support the use of the B cell-depleting antibody rituximab in steroid-sensitive nephrotic syndrome. Finally there is a meta-analysis of six studies suggesting an increase in the incidence of focal and segmental glomerulosclerosis in steroid-sensitive nephrotic syndrome over the last 20 years. SUMMARY: Progress has been made towards elucidating the cause of steroidsensitive nephrotic syndrome. Data from adequately powered randomized controlled trials are still required to evaluate therapies for frequently relapsing and steroid-dependent steroidsensitive nephrotic syndrome. [References: 56] Publication Type Journal Article. Review. <14> Unique Identifier 18304155 Status MEDLINE Authors Shah KN. Yan AC. Authors Full Name Shah, Kara N. Yan, Albert C. Institution Pediatric Dermatology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. Title Acquired zinc deficiency acrodermatitis associated with nephrotic syndrome. [Review] [25 refs] Source Pediatric Dermatology. 25(1):56-9, 2008 Jan-Feb. Abstract We present a child with new-onset nephrotic syndrome, acrodermatitis, low serum zinc levels and decreased serum alkaline phosphatase. A diagnosis of acquired zinc deficiency acrodermatitis was made. Oral zinc supplementation led to rapid clinical resolution. The etiology of zinc deficiency in nephrotic syndrome remains unknown. [References: 25] Publication Type Case Reports. Journal Article. Review. <15> Unique Identifier 18254005 Status MEDLINE Authors Hodson EM. Willis NS. Craig JC. Authors Full Name Hodson, E M. Willis, N S. Craig, J C. Institution Children's Hospital at Westmead, Centre for Kidney Research, Locked Bag 4001, Westmead, NSW, Australia, 2145. Elisah@chw.edu.au Title Non-corticosteroid treatment for nephrotic syndrome in children. [Review] [96 refs][Update of Cochrane Database Syst Rev. 2005;(2):CD002290; PMID: 15846634] Source Cochrane Database of Systematic Reviews. (1):CD002290, 2008. Abstract BACKGROUND: Eighty to 90% of children with steroid-sensitive nephrotic syndrome (SSNS) have relapses. About half relapse frequently and are at risk of the adverse effects of corticosteroids. Non-corticosteroid immunosuppressive agents are used to prolong periods of remission in these children, however these agents have significant potential adverse effects. Currently there is no consensus as to the most appropriate second line agent in children who are steroid sensitive, but who continue to relapse. OBJECTIVES: To evaluate the benefits and harms of non-corticosteroid immunosuppressive agents in relapsing SSNS in children. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, reference lists, conference abstracts and contact with known investigators. Search date: September 2007 SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs were included if they compared non-corticosteroid agents with placebo, prednisone or no treatment, different doses and/or durations of the same noncorticosteroid agent, different non-corticosteroid agents. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study quality and extracted data. Statistical analyses were performed using a random effects model and results expressed as relative risk (RR) with 95% confidence intervals (CI). MAIN RESULTS: We identified 26 studies (1173 children). Cyclophosphamide (RR 0.44, 95% CI 0.26 to 0.73) and chlorambucil (RR 0.15, 95% CI 0.02 to 0.95) significantly reduced the relapse risk at six to twelve months compared with prednisone alone. There was no difference in relapse risk at two years between chlorambucil and cyclophosphamide (RR 1.31, 95% CI 0.80 to 2.13). There was no difference at one year between intravenous and oral cyclophosphamide (RR 0.99, 95% CI 0.76 to 1.29). Cyclosporin was as effective as cyclophosphamide (RR 1.07, 95% CI 0.48 to 2.35) and chlorambucil (RR 0.82, 95% CI 0.44 to 1.53) and levamisole (RR 0.43, 95% CI 0.27 to 0.68) was more effective than steroids alone but the effects were not sustained once treatment was stopped. There was no difference in the risk for relapse between mycophenolate mofetil and cyclosporin (RR 5.00, 95% CI 0.68 to 36.66) but CI were large. Mizoribine and azathioprine were no more effective than placebo or prednisone alone in maintaining remission. AUTHORS' CONCLUSIONS: Eight week courses of cyclophosphamide or chlorambucil and prolonged courses of cyclosporin and levamisole reduce the risk of relapse in children with relapsing SSNS compared with corticosteroids alone. Clinically important differences in efficacy are possible and further comparative studies are still needed. [References: 96] Publication Type Journal Article. Meta-Analysis. Review. <16> Unique Identifier 18245896 Status MEDLINE Authors Chiu MC. Authors Full Name Chiu, Man-chun. Institution Paediatric Nephrology Center, Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital, Hong Kong. firstname.lastname@example.org Title Management strategy for idiopathic nehprotic syndrome in children. [Review] [20 refs] Source Zhong Nan da Xue Xue Bao. Yi Xue Ban = Journal of Central South University. Medical Sciences. 33(1):1-7, 2008 Jan. Abstract Corticosteroid, alkylating agents, like cyclophosphamide and chlorambucil, have been used to treat idiopathic nephrotic syndrome for more than fifty years, changing the outcome of these children. However, with long-term use of steroid, especially high dosages, they have unbearable side effects. Newer agents like cyclosporine A, levamisole, tacrolimus, mycophenolate mofetil, have been used to spare those unwanted side effects. In the choice of drugs, the benefits obtained will have to be evaluated against possible side effects, with drug cost also taken into consideration. Though most steroid sensitive nephrotic children may run a relapsing course, have a good prognosis with many becoming non-relapsers or infrequent relapsers in adulthood, the treatment approach should aim at using the minimal amount of drug required to keep patient in remission to tie them over childhood. As for steroid resistant nephrotic syndrome children, especially for focal segmental glomerulosclerosis (FSGS), because of possible grave prognosis of going into end-stage renal failure, more aggressive approach should be adopted, including the use of strong immunosuppressants, such as, cyclosporine, tacrolimus, or mycophenolate mofetil if necessary. The long-term goals of treatment, other than those of physical and medical conditions, should also consider the growth, education, and psychological impact of the disease and side effects of drugs on the child, especially during an adolescent period, so as to allow them having normal development into adulthood. [References: 20] Publication Type Journal Article. Review. <17> Unique Identifier 18162004 Status MEDLINE Authors Ehrich JH. Pape L. Schiffer M. Authors Full Name Ehrich, Jochen H H. Pape, Lars. Schiffer, Mario. Institution Department of Pediatric Nephrology, Hannover Medical School, Hannover, Germany. email@example.com Title Corticosteroid-resistant nephrotic syndrome with focal and segmental glomerulosclerosis : an update of treatment options for children. [Review] [142 refs] Source Paediatric Drugs. 10(1):9-22, 2008. Abstract Corticosteroid-resistant nephrotic syndrome (CRNS) with focal and segmental glomerulosclerosis (FSGS) is a heterogeneous disorder and the most severe and frequent type of all glomerulopathies in children leading to end-stage renal failure. The podocyte is at the center of development and progress of FSGS; this unique cell type plays a major role in the integrity of glomerular structure and permeability. The rate of complete remission of CRNS after induction therapy using different immunosuppressant agents is reported to range between 30% and 84%, depending on the treatment schedule and on the underlying defects of FSGS. Children with genetic types of FSGS barely respond to immunosuppressant therapies and over-treatment prior to transplantation should be avoided. The response of children with an idiopathic type of FSGS to immunosuppressants is superior to those with genetic FSGS. However, many children with idiopathic FSGS do not enter complete remission if they are under-treated, for example, with short-term immunosuppressant monotherapies. If immunosuppressant treatment fails, these patients will have to undergo renal transplantation. However, as unknown pathogenetic mechanisms may persist, more than one-third of these patients with idiopathic FSGS develop a rapid recurrence of CRNS that responds poorly to further long-term therapeutic attempts. In contrast with previously published data, this review takes into account recently identified genetic etiologies of CRNS, and superior results with long-term combination therapy in idiopathic forms to avoid over- and under-treatment. [References: 142] Publication Type Journal Article. Review. <18> Unique Identifier 18060371 Status MEDLINE Authors Ciszak L. Pawlak E. Kosmaczewska A. Potoczek S. Frydecka I. Authors Full Name Ciszak, Lidia. Pawlak, Edyta. Kosmaczewska, Agata. Potoczek, Stanislaw. Frydecka, Irena. Institution Laboratory of Immunopathology, Department of Experimental Therapy, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, R. Weigla 12, 53-114, Wroclaw, Poland. firstname.lastname@example.org Title Alterations in the expression of signal-transducing CD3 zeta chain in T cells from patients with chronic inflammatory/autoimmune diseases. [Review] [114 refs] Source Archivum Immunologiae et Therapiae Experimentalis. 55(6):373-86, 2007 Nov-Dec. Abstract The CD3 zeta chain, a component of the T cell receptor (TCR)/CD3 complex, is considered to be a limiting factor in the assembly and transport of the TCR/CD3 complex to the cell surface and is crucial to receptor signaling function. Recent studies have demonstrated altered expression and function of this signal transduction molecule in T and natural killer cells in patients with chronic inflammatory/autoimmune diseases. In this review, current knowledge concerning the expression of CD3 zeta chain as well as the mechanisms responsible for abnormal expression of this molecule in systemic lupus erythematosus, rheumatoid arthritis, and childhood idiopathic nephrotic syndrome are summarized. [References: 114] Publication Type Journal Article. Research Support, Non-U.S. Gov't. Review. <19> Unique Identifier 17943754 Status MEDLINE Authors Hodson EM. Willis NS. Craig JC. Authors Full Name Hodson, E M. Willis, N S. Craig, J C. Institution Children's Hospital at Westmead, Centre for Kidney Research, Locked Bag 4001, Westmead, NSW, Australia, 2145. Elisah@chw.edu.au Title Corticosteroid therapy for nephrotic syndrome in children. [Review] [71 refs][Update of Cochrane Database Syst Rev. 2005;(1):CD001533; PMID: 15674881] Source Cochrane Database of Systematic Reviews. (4):CD001533, 2007. Abstract BACKGROUND: In nephrotic syndrome (NS) protein leaks from the blood to the urine through the glomeruli resulting in hypoproteinaemia and generalised oedema. While the majority of children with NS respond to corticosteroids, 70% experience a relapsing course. Corticosteroids have reduced the mortality rate to around 3%. However corticosteroids have well recognised potentially serious adverse effects such as obesity, poor growth, hypertension, diabetes mellitus and osteoporosis. OBJECTIVES: To determine the benefits and harms of corticosteroid regimens in preventing relapse in children with steroid sensitive NS (SSNS). SEARCH STRATEGY: We searched CENTRAL, Cochrane Renal Group Specialised Register, MEDLINE and EMBASE without language restriction, reference lists of articles and contact with known investigators. Date of last search: December 2006 SELECTION CRITERIA: Randomised controlled trials performed in children (three months to 18 years) in their initial or subsequent episode of SSNS, comparing different durations, total doses or other dose strategies using any corticosteroid agent, with outcome data at six months or more. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. Results were expressed as relative risk (RR) with 95% confidence intervals (CI) or mean difference (WMD). Meta-regression was used to explore potential between-study differences due to baseline risk of relapse, study quality and interventions. MAIN RESULTS: Twenty four trials were identified. Six trials comparing two months of prednisone or prednisolone with three months or more in the first episode showed longer duration significantly reduced the risk of relapse at 12 to 24 months (RR 0.70, 95% CI 0.58 to 0.84). There was an inverse linear relationship between treatment duration and risk of relapse (RR = 1.26 - 0.112 duration; P = 0.03). Four trials showed that six months of prednisone was more effective than three months in reducing the risk for relapse (RR 0.57; 95% CI 0.45 to 0.71). Deflazacort was significantly more effective in maintaining remission than prednisone in children who frequently relapsed in a single study (RR 0.44, 95% CI 0.25 to 0.78). There were no increases in adverse events. AUTHORS' CONCLUSIONS: Children in their first episode of SSNS should be treated for at least three months with an increase in benefit for up to seven months of treatment. For a baseline risk for relapse following the first episode of 60% with two months of therapy, daily prednisone or prednisolone given for four weeks followed by alternate-day therapy for six months would reduce the number of children relapsing by 33%. [References: 71] Publication Type Journal Article. Meta-Analysis. Review. <20> Unique Identifier 17551756 Status MEDLINE Authors Borges FF. Shiraichi L. da Silva MP. Nishimoto EI. Nogueira PC. Authors Full Name Borges, Fabio Fernandes. Shiraichi, Luciana. da Silva, Marcos Paulo Hippolito. Nishimoto, Eduardo Isaac. Nogueira, Paulo Cesar Koch. Institution Faculdade de Ciencias Medicas de Santos, UNILUS, Sao Paulo, Brazil. Title Is focal segmental glomerulosclerosis increasing in patients with nephrotic syndrome?. [Review] [18 refs] Source Pediatric Nephrology. 22(9):1309-13, 2007 Sep. Abstract Idiopathic nephrotic syndrome in children has conventionally been associated with minimal change disease. However, recent reports have conflictingly suggested that the frequency of focal segmental glomerulosclerosis (FSGS) in children might be on the increase, as has occurred in adults. The aim of the present work was to review the medical literature to ascertain whether an increase in the frequency of FSGS is occurring and, if so, to quantify such increase. We reviewed the studies comparing the frequency of FSGS in two consecutive periods over the past three decades (period 1 versus period 2). We pooled the data of the studies and then estimated FSGS frequency in two ways: (a) including in the denominator all patients with nephrotic syndrome and (b) including only patients who had undergone kidney biopsy. Both analyses were aimed to determine the odds ratio of FSGS occurrence in the second period. Six studies fulfilled the inclusion criteria, involving 1,149 patients with nephrotic syndrome. Four studies were used to calculate FSGS frequency, including in the denominator all nephrotic patients (n = 885), yielding an odds ratio of 2.22 (95% CI = 1.18-4.18). The analysis combining five studies with the number of biopsies in the denominator (n = 603) produced an odds ratio of 1.98 (95% CI = 1.12-3.50). These results suggest that a shift in the pathological pattern of nephrotic syndrome in children might be occurring, resulting in an increase in FSGS frequency. This hypothesis has major clinical significance due to the poorer prognosis associated with FSGS. [References: 18] Publication Type Journal Article. Review. <21> Unique Identifier 17594193 Status MEDLINE Authors Westhoff TH. van der Giet M. Authors Full Name Westhoff, Timm H. van der Giet, Markus. Institution Charite--Campus Benjamin Franklin, Centrum 10--Nephrology, Hindenburgdamm 30, Berlin, Germany. email@example.com Title Tacrolimus in the treatment of idiopathic nephrotic syndrome. [Review] [100 refs] Source Expert Opinion on Investigational Drugs. 16(7):1099-110, 2007 Jul. Abstract The immunosuppressant tacrolimus (FK-506) is a calcineurin inhibitor with a widespread use for the prevention of graft rejection in transplantation medicine. Tacrolimus inhibits the activation of an essential transcription factor for the transcription of cytokine genes in T cells leading to a decreased production of cytokines such as IL-2 and IFN-gamma. As T-cell activation plays a crucial role in the pathogenesis of inflammatory glomerular diseases, there is an increasing number of reports on the use of tacrolimus in nephrotic syndrome. In idiopathic nephrotic syndrome, corticosteroid treatment constitutes the first-line therapy to achieve remission. In the case of steroid resistance or steroid dependence, alternative immunosuppressive strategies are needed. Cyclophosphamide and ciclosporin are well-established drugs in this condition. The present article reviews the pharmacodynamics, pharmacokinetics, safety and clinical efficacy of tacrolimus in steroid-resistant and steroid-dependent nephrotic syndrome. [References: 100] Publication Type Journal Article. Review. <22> Unique Identifier 17537341 Status MEDLINE Authors Colquitt JL. Kirby J. Green C. Cooper K. Trompeter RS. Authors Full Name Colquitt, J L. Kirby, J. Green, C. Cooper, K. Trompeter, R S. Institution Southampton Health Technology Assessments Centre, University of Southampton, UK. Title The clinical effectiveness and cost-effectiveness of treatments for children with idiopathic steroid-resistant nephrotic syndrome: a systematic review. [Review] [70 refs] Source Health Technology Assessment (Winchester, England). 11(21):iii-iv, ix-xi, 1-93, 2007. Abstract OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of treatments for children with idiopathic steroid-resistant nephrotic syndrome (SRNS). DATA SOURCES: Electronic databases from inception to February 2006, bibliographies of studies, and experts in the field. REVIEW METHODS: Studies were selected, quality assessed and data were extracted using recognised methods agreed a priori. Meta-analysis was undertaken where appropriate using the random effects model. Where data allowed, subgroup analysis was undertaken according to renal histopathology. RESULTS: Two systematic reviews and 11 trials were included in the clinical effectiveness review; however, the quality of reporting and methodology of the included studies was generally poor. No economic evaluations were identified. No statistically significant difference in remission rates was found between cyclophosphamide plus prednisone and prednisone alone for all children or those with focal segmental glomerulosclerosis (FSGS), also the time to response was statistically significantly less with cyclophosphamide (38.4 days versus 95.5 days). Remission rates were not statistically significantly different between intravenous and oral cyclophosphamide. Vomiting was common with intravenous cyclophosphamide, while pneumonia and alopecia occurred in the oral group. Ciclosporin statistically significantly increased the number of children with complete remission compared with placebo or supportive treatment, but not for the FSGS subgroup, adverse effects including infection and hypertension differed little between groups. No differences were found between azathioprine and placebo, with about 13% of each group having remission. Complete or partial remission occurred in six out of seven patients on the 18-month methylprednisolone regimen and three out of five patients on the 6-month regimen, for both groups renal function improved and adverse events such as hypertension and frequent infections occurred. Intravenous dexamethasone and methylprednisolone produced similar complete remission rates, partial remission rates, median time to response (about 10 days) and total number of adverse events, with hypertension as the most common. Six-hour urinary albumin and urinary albumin to creatinine ratio decreased statistically significantly with high-dose but not low-dose enalapril. Tuna fish oil was not associated with any statistically significant improvements in proteinuria, creatinine clearance, serum creatinine or lipid profiles compared with placebo. A very limited literature was found on costs associated with SRNS in children. The pharmaceutical cost of treatment varied considerably: an 8-week course of cyclophosphamide cost less than 6 pounds, while a course of ciclosporin cost almost 900 pounds per year. Treatment with tacrolimus, an alternative to ciclosporin, was estimated to cost in excess of 3400 pounds per year. Healthcare medical management costs were estimated; varying by treatment strategy, they ranged from 250 pounds to 930 pounds per year in patients not experiencing complications. Other longer term costs may also be incurred. Lack of data meant that cost-effectiveness modelling was not feasible. CONCLUSIONS: The clinical effectiveness literature on treatments for idiopathic SRNS in children is very limited. The available evidence suggests a beneficial effect of ciclosporin on remission rates and of cyclophosphamide on time to remission; however, the strength of the conclusions drawn is limited by the poor quality of the included studies. The other treatments included in this review were each evaluated by only one study, and none found a statistically significant effect. There is insufficient evidence to determine whether or not there is a clinically significant difference. The available data on costs and outcomes are sparse and do not permit the reliable modelling of the cost-effectiveness of treatments for SRNS at present. A modelling framework is suggested, should more relevant data become available. A well-designed adequately powered randomised controlled trial comparing ciclosporin with other treatments in children with SRNS without genetic mutation is required. [References: 70] Publication Type Journal Article. Review. <23> Unique Identifier 17364996 Status MEDLINE Authors Zaffanello M. Franchini M. Authors Full Name Zaffanello, Marco. Franchini, Massimo. Institution Department of Pediatrics, University of Verona, Verona, Italy. firstname.lastname@example.org Title Thromboembolism in childhood nephrotic syndrome: a rare but serious complication. [Review] [54 refs] Source Hematology. 12(1):69-73, 2007 Feb. Abstract The main clinical features of nephrotic syndrome (NS) are heavy proteinuria, hypoalbuminemia, hyperlipidemia and edema. In addition, multiple abnormalities in the coagulation pathway may be a consequence of the NS. Both arterial and venous thromboembolic complications (TEC) are relatively common and serious consequences of NS. In addition, arterial and venous thrombosis might be unexpected events during an exacerbation of NS. Embolic episodes may manifest in different regions of the body such as the brain or the lung. Hence, predisposing factors, personal and family history of TEC, thrombosis location and evolution should be always investigated in children with NS. [References: 54] Publication Type Journal Article. Review. <24> Unique Identifier 17186280 Status MEDLINE Authors Fine RN. Authors Full Name Fine, Richard N. Institution School of Medicine, Stony Brook University, Stony Brook, NY 11794-8111, USA. email@example.com Title Recurrence of nephrotic syndrome/focal segmental glomerulosclerosis following renal transplantation in children. [Review] [40 refs] Source Pediatric Nephrology. 22(4):496-502, 2007 Apr. Other ID Source: NLM. PMC1805045 Abstract The incidence of recurrence of nephrotic syndrome/focal segmental glomerulosclerosis (NS/FSGS) is variable (~30%). The incidence of recurrence is less in African-Americans than in whites and Hispanics. Graft survival rates are decreased in recipients with FSGS, especially if remission of the NS is not achieved in those with recurrence. Although controversial, the use of living donor (LD) transplants are not contraindicated; however, obligatory heterozygote parental grafts with a podocin mutation should be used with caution. Optimal treatment to induce a remission post-transplant has not been delineated. Pre-transplant and/or prophylactic posttransplant pre-operative plasmapheresis (PP) for high-risk patients--especially those with recurrence in a previous graft--may be promising. An international multicenter controlled study is required to delineate the optimal approach to prevent and/or treat the recurrence of NS/FSGS. [References: 40] Publication Type Journal Article. Review. <25> Unique Identifier 17285887 Status MEDLINE Authors Jackson LW. Authors Full Name Jackson, Lori Williams. Institution University of Wisconsin Children's Hospital, USA. Title Congenital nephrotic syndrome. [Review] [36 refs] Source Neonatal Network - Journal of Neonatal Nursing. 26(1):47-55, 2007 Jan-Feb. Abstract When presented with an edematous infant who may be experiencing a severe infection, particularly an unusual one, it is important to include nephrotic syndrome in the differential diagnosis. Because drastic measures may be required to manage this illness, it is important to be able to recognize symptoms, compile needed diagnostic data, and commence appropriate treatment. A referred pediatric nephrologist can aid in diagnosis, direct management, and educate and support parents. The nephrologist is also instrumental in guiding ongoing care and preparing the infant for transplantation when it becomes necessary. [References: 36] Publication Type Journal Article. Review. <26> Unique Identifier 17225845 Status MEDLINE Authors Anochie I. Eke F. Okpere A. Authors Full Name Anochie, Ifeoma. Eke, Felicia. Okpere, Augustina. Institution Department of Poediatrics, University of Port Harcourt Teaching Hospital, Port Harcourt, Rivers State, Nigeria. firstname.lastname@example.org Title Childhood nephrotic syndrome: change in pattern and response to steroids. [Review] [44 refs] Source Journal of the National Medical Association. 98(12):1977-81, 2006 Dec. Other ID Source: NLM. PMC2569667 Abstract BACKGROUND: In our center, childhood nephrotic syndrome (NS) had been reported for over a decade to be steroid sensitive contrary to reports in other parts of Nigeria. The purpose of this study was to determine if there are changes in presentation and response to steroids, with reviews of the literature on NS. METHODS: Analysis of 28 patients seen at the University of Port Harcourt Teaching Hospital, Nigeria, from 1999-2004 with the diagnosis of NS was performed. RESULTS: There were 14 girls and 14 boys with NS. The peak age was 1-4 years. Twenty (71.4%) children had idiopathic nephrotic syndrome (INS). Four had chronic renal failure, one had sickle cell disease (HbSS), two were positive to human immunodeficiency virus (HIV) 1 and 2, and one had pulmonary tuberculosis. Anemia was found in 13 patients, while 17 had Plasmodium falciparum. Plasmodium malariae and hepatitis-B surface antigen were not isolated. Renal biopsy was performed in four patients and revealed minimal-change disease in one child, focal segmental glomerulosclerosis in two and no conclusive result in one patient. Oral prednisolone was used in INS. After one month of therapy, 16 of 20 responded, of which 12 (75%) were <5 years. The NS relapsed in 15 of 16 steroid-sensitive patients. Cyclophosphamide and levamisole were used in four and one patients with FRNS, respectively. Four (14.3%) patients died; all were secondary NS. CONCLUSION: INS remains common in our center, and the majority respond to steroid therapy [References: 44] Publication Type Journal Article. Review. <27> Unique Identifier 17044482 Status MEDLINE Authors Kanjanabuch T. Lewsuwan S. Kitiyakara C. Cheunsuchon B. Eiam-Ong S. Authors Full Name Kanjanabuch, Talerngsak. Lewsuwan, Songkiat. Kitiyakara, Chagriya. Cheunsuchon, Boonyarit. Eiam-Ong, Somchai. Institution Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University Hospital, Bangkok, Thailand. email@example.com Title Update in pathophysiology and histopathology of focal segmental glomerulosclerosis. [Review] [56 refs] Source Journal of the Medical Association of Thailand. 89 Suppl 2:S262-79, 2006 Aug. Abstract Focal segmental glomerulosclerosis (FSGS) is the leading cause of nephrotic syndrome in an adult worldwide. The prevalence of FSGS is estimated as being 20-30% in adults over the age of 15 years and slightly higher (30-35%) in the elderly (age > 60 years). The diagnosis solely relies on pathologic findings, which sclerosis involves some, but not all glomeruli (focal), and sclerosis affects a portion, but not the entire, glomerular tuft (segmental). The pathogenesis remains inconclusive but podocyte injury has been postulated. Even though steroid is the mainstay treatment, only 20-40% of patients are complete respond. [References: 56] Publication Type Journal Article. Review. <28> Unique Identifier 16691407 Status MEDLINE Authors Fluss J. Geary D. deVeber G. Authors Full Name Fluss, Joel. Geary, Denis. deVeber, Gabrielle. Institution Division of Pediatric Neurology, The Hospital for Sick Children, Toronto, ON, Canada. Title Cerebral sinovenous thrombosis and idiopathic nephrotic syndrome in childhood: report of four new cases and review of the literature. [Review] [52 refs] Comments Comment in: Eur J Pediatr. 2007 Jul;166(7):757-8; author reply 759; PMID: 17447084] Source European Journal of Pediatrics. 165(10):709-16, 2006 Oct. Abstract INTRODUCTION: Nephrotic children are prone to develop thromboembolic complications secondary to an acquired hypercoagulable state. Cerebral sinovenous thrombosis (CSVT) is increasingly recognised in this population, but clinical characteristics and outcome are not well documented. PATIENTS AND METHODS: The database of the Canadian Pediatric Ischemic Stroke Registry (Toronto Site) containing prospectively enrolled children from 1992-2004 with CSVT identified four children with NS. A pooled literature analysis retrieved 17 additional cases reports. RESULTS: CSVT presented in the majority of cases during the first flare or within 6 months after the onset of NS and was found to occur more often in SSNS/SDNS (n=13) than in SRNS (n=4). Clinical manifestations were non-specific and consisted primarily of seizures (n=8) and signs of raised intracranial pressure (n=16). Imaging studies revealed a predilection for superior sagittal sinus involvement (n=21) and rare parenchymal lesions (n=4). The most consistent biological risk factors were a severe hypoalbuminaemia (n=14) and, to a lesser extent, decreased antithrombin (AT) levels (n=9/16). Deficiency of other coagulation inhibitors (protein S, protein C) was not identified. Inherited thrombophilia was documented in a single case, suggesting that acquired, more than genetic, coagulation factors are involved. Anticoagulation was safe, and the outcome was good in most patients, and no recurrence of thrombotic event was reported. DISCUSSION: In conclusion, CSVT is now a well-described complication of NS with potential morbidity. A high index of suspicion is required, especially in young children with NS presenting neurological symptoms. Reliable biological predictors of CSVT are lacking. [References: 52] Publication Type Case Reports. Journal Article. Review. <29> Unique Identifier 16898477 Status MEDLINE Authors Feber J. Filler G. Authors Full Name Feber, Janusz. Filler, Guido. Institution Division of Nephrology, Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Canada. Title Nephrotic syndrome in children: should we always use steroids for the initial therapy?. [Review] [30 refs] Source Przeglad Lekarski. 63 Suppl 3:12-4, 2006. Publication Type Journal Article. Review. <30> Unique Identifier 16625586 Status MEDLINE Authors Hodson EM. Habashy D. Craig JC. Authors Full Name Hodson, E M. Habashy, D. Craig, J C. Institution Children's Hospital at Westmead, Centre for Kidney Research, Locked Bag 4001, Westmead, NSW, Australia, 2145. Elisah@chw.edu.au Title Interventions for idiopathic steroid-resistant nephrotic syndrome in children. [Review] [38 refs][Update of Cochrane Database Syst Rev. 2004;(2):CD003594; PMID: 15106208] Source Cochrane Database of Systematic Reviews. (2):CD003594, 2006. Abstract BACKGROUND: The majority of children who present with their first episode of nephrotic syndrome, achieve remission with corticosteroid therapy. Children who fail to respond may be treated with immunosuppressive agents such as cyclophosphamide, chlorambucil or cyclosporin, or with non-immunosuppressive agents such as ACE inhibitors. Optimal combinations of these agents with the least toxicity remain to be determined. OBJECTIVES: To evaluate the benefits and harms of interventions used to treat idiopathic steroid resistant nephrotic syndrome (SRNS) in children. SEARCH STRATEGY: Randomised controlled trials (RCTs) were identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, reference lists of articles and abstracts from conference proceedings. Date of most recent search: June 2005 SELECTION CRITERIA: RCTs and quasi-RCTs were included if they compared different immunosuppressive agents or non-immunosuppressive agents with placebo, prednisone or other agent given orally or parenterally in children aged three months to 18 years with SRNS. DATA COLLECTION AND ANALYSIS: Two reviewers independently searched the literature, determined trial eligibility, assessed quality, extracted data and entered it in RevMan. For dichotomous outcomes, results were expressed as relative risk (RR) and 95% confidence intervals (CI). Data were pooled using the random effects model. MAIN RESULTS: Eleven RCTs (312 children) were included. Cyclosporin when compared with placebo or no treatment significantly increased the number of children who achieved complete remission (three trials, 49 children: RR for persistent nephrotic syndrome 0.64, 95% CI, 0.47 to 0.88). There was no significant difference in the number of children who achieved complete remission between oral cyclophosphamide with prednisone and prednisone alone (two trials, 91 children: RR 1.01, 95% CI 0.74 to 1.36), between intravenous cyclophosphamide and oral cyclophosphamide (one study, 11 children: RR 0.09, 95% CI 0.01 to 1.39) and between azathioprine with prednisone and prednisone alone (one trial 31 children: RR 1.01, 95% CI 0.77 to 1.32). ACE inhibitors significantly reduced proteinuria (two trials, 70 children). After 12 weeks of treatment fosinopril reduced proteinuria by 0.95 g/24 h (95% CI -1.21 to -0.69). No RCTs were identified comparing combination regimens comprising high dose steroids, alkylating agents or cyclosporin with single agents, placebo or no treatment. AUTHORS' CONCLUSIONS: Further adequately powered and well designed RCTs are needed to confirm the efficacy of cyclosporin and to evaluate other regimens for idiopathic SRNS including high dose steroids with alkylating agents or cyclosporin. [References: 38] Publication Type Journal Article. Meta-Analysis. Review.