• Clinical and Experimental Pediatrics
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• v.54 no.8
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• pp.317-321
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• 2011

Children who suffer from steroid-resistant nephrotic syndrome (SRNS) require aggressive treatment to achieve remission. When intravenous high-dose methylprednisolone fails, calcineurin inhibitors, such as cyclosporine and tacrolimus, are used as the first line of treatment. A significant number of patients with SRNS progress to end-stage renal disease if remission is not achieved. For these children, renal replacement therapy can also be problematic; peritoneal dialysis may be accompanied by significant protein loss through the peritoneal membrane, and kidney allograft transplantation may be complicated by recurrence of SRNS. Plasmapheresis and rituximab were initially used for treatment of recurrent SRNS after transplantation; these are now under consideration as rescue therapies for refractory SRNS. Although the prognosis of SRNS is complicated and unfavorable, intensive treatment in the early stages of the disease may achieve remission in more than half of the patients. Therefore, timely referral of pediatric SRNS patients to pediatric nephrology specialists for histological and genetic diagnosis and treatment is highly recommended.

• Childhood Kidney Diseases
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• v.2 no.2
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• pp.183-186
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• 1998

Steroid Resistant Nephrotic Syndrome(SRNS) in children has poor prognosis and no effective therapy. In 1994, Ravi Elhence have reported that IV cyclophosphamide therapy was effective against SRNS of children. So, we evaluated the efficacy of IV cyclophosphamide in 3 children with biopsy proven steroid-resistant MCNS. And the result was the rapeutic failure. In conclusion, IV cyclophosphamide therapy wass not effective against SRNS of children.

• Childhood Kidney Diseases
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• v.13 no.2
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• pp.189-196
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• 2009

Purpose : The pathophysiologic mechanism of nephrotic syndrome is not yet known clearly. At least in some cases, certain 'circulating factors' are thought to increase the glomerular protein permeability. Considering the systemic effect of the circulating factor on peritoneal membrane, we evaluated the loss of protein through peritoneal membrane in patients on peritoneal dialysis due to the end stage renal disease (ESRD) caused by steroid resistant nephrotic syndrome (SRNS). Methods : We retrospectively reviewed the medical records of 26 pediatric patients on peritoneal dialysis ensued during the period from 2001 to 2007 at our clinic. Twelve patients had SRNS, while 14 patients had ESRD caused by the congenital anomalies of urinary system. Results : While the other parameters including nPNA indicating the adequacy of protein intake were similar between the two groups, serum albumin was lower in SRNS patients than the non-SRNS patients ($3.7{\pm}0.3$ g/dL vs. $4.0{\pm}0.4$ g/dL, P=0.021). Peritoneal protein loss was higher in SRNS patients than in non-SRNS patients ($3,044.4{\pm}837.6\;mg/m^2$/day vs. $1,791.6{\pm}1,244.0\;mg/m^2$/day, P=0.007). The protein permeability of the peritoneal membrane measured by the ratio of total protein concentration in dialysate to plasma was twice as high in SRNS patients as the non-SRNS ($1.06{\pm}0.46%$ vs. $0.58{\pm}0.43%$, P=0.010). After 1 year, peritoneal protein loss increased in both patient groups, but to a significantly greater degree in non-SRNS patient (P=0.023). Conclusion : The results of our study support the notion that in nephrotic syndrome there are some 'circulating factors' with the systemic effect. Since the greater protein loss through peritoneal membrane in SRNS was confirmed in this study, more meticulous nutritional support and close monitoring on the nutrition are required in these patients.

• Clinical and Experimental Pediatrics
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• v.64 no.7
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• pp.355-363
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• 2021

Background: Nephrotic syndrome (NS) is a common renal disorder in children attributed to podocyte injury. However, children with the same diagnosis have markedly variable treatment responses, clinical courses, and outcomes, suggesting molecular heterogeneity. Purpose: This study aimed to explore the molecular responses of podocytes to nephrotic plasma to identify specific genes and signaling pathways differentiating various clinical NS groups as well as biological processes that drive injury in normal podocytes. Methods: Transcriptome profiles from immortalized human podocyte cell line exposed to the plasma of 8 subjects (steroid-sensitive nephrotic syndrome [SSNS], n=4; steroid-resistant nephrotic syndrome [SRNS], n=2; and healthy adult individuals [control], n=2) were generated using microarray analysis. Results: Unsupervised hierarchical clustering of global gene expression data was broadly correlated with the clinical classification of NS. Differential gene expression (DGE) analysis of diseased groups (SSNS or SRNS) versus healthy controls identified 105 genes (58 up-regulated, 47 down-regulated) in SSNS and 139 genes (78 up-regulated, 61 down-regulated) in SRNS with 55 common to SSNS and SRNS, while the rest were unique (50 in SSNS, 84 genes in SRNS). Pathway analysis of the significant (P≤0.05, -1≤ log2 FC ≥1) differentially expressed genes identified the transforming growth factor-β and Janus kinase-signal transducer and activator of transcription pathways to be involved in both SSNS and SRNS. DGE analysis of SSNS versus SRNS identified 2,350 genes with values of P≤0.05, and a heatmap of corresponding expression values of these genes in each subject showed clear differences in SSNS and SRNS. Conclusion: Our study observations indicate that, although podocyte injury follows similar pathways in different clinical subgroups, the pathways are modulated differently as evidenced by the heatmap. Such transcriptome profiling with a larger cohort can stratify patients into intrinsic subtypes and provide insight into the molecular mechanisms of podocyte injury.

• Childhood Kidney Diseases
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• v.1 no.2
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• pp.123-129
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• 1997

Purpose : The Childhood Steroid Resistant Nephrotic Syndrome (SRNS) has a poor prognosis and there has been no effective therapy against SRNS of children. In 1990, Mendoza have reported that methylprednisolone pulse therapy was effective against SRNS of children. But in 1992, Waldo have reported that methylprednisolone pulse therapy was not as effective as in the report of Mendoza. So, retrospectively, we have studied 20 korean children with SRNS to evaluate the effect of methylprednisolone pulse therapy, Methods : Mothylprednisolone pulse therapy were given to 20 korean children with SRNS who admitted to Seoul National University Hospital from 1990 to 1995 and follow up was done Results : 1) During methylprednisolone pulse therapy, remission of nephrotic syndrome was induced in 45% of patients. 2) during follow up after the end of methylprednisolone pulse therapy, remission of nephrotic syndrome was maintained in 45% of patients. 3) 25% of patients has progressed to chronic renal failure. Conclusion : We think that the methylprednisolone pulse therapy is a effective therapy against SRNS of children with the 45%, remission rate of of SRNS in Korean Children

• Childhood Kidney Diseases
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• v.23 no.2
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• pp.86-92
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• 2019

Steroid-resistant nephrotic syndrome (SRNS) has long been a challenge for clinicians due to its poor responsiveness to immunosuppressants, and rapid progression to end-stage renal disease. Identifying a monogenic cause for SRNS may lead to a better understanding of podocyte structure and function in the glomerular filtration barrier. This review focuses on genes associated with slit diaphragm, actin cytoskeleton, transcription factors, nucleus, glomerular basement membrane, mitochondria, and other proteins that affect podocyte biology.

• International Journal of Contents
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• v.6 no.4
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• pp.30-34
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• 2010

Effective job scheduling scheme is a crucial part of complex heterogeneous distributed systems. Gang scheduling is a scheduling algorithm for grid systems that schedules related grid jobs to run simultaneously on servers in different local sites. In this paper, we address grid jobs (gangs) schedule modeling using Stochastic reward nets (SRNs), which is concerned for static and dynamic scheduling policies. SRN is an extension of Stochastic Petri Net (SPN) and provides compact modeling facilities for system analysis. Threshold queue is adopted to smooth the variations of performance measures. System throughput and response time are compared and analyzed by giving reward measures in SRNs.

• Clinical and Experimental Pediatrics
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• v.60 no.3
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• pp.55-63
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• 2017

Advances in podocytology and genetic techniques have expanded our understanding of the pathogenesis of hereditary steroid-resistant nephrotic syndrome (SRNS). In the past 20 years, over 45 genetic mutations have been identified in patients with hereditary SRNS. Genetic mutations on structural and functional molecules in podocytes can lead to serious injury in the podocytes themselves and in adjacent structures, causing sclerotic lesions such as focal segmental glomerulosclerosis or diffuse mesangial sclerosis. This paper provides an update on the current knowledge of podocyte genes involved in the development of hereditary nephrotic syndrome and, thereby, reviews genotype-phenotype correlations to propose an approach for appropriate mutational screening based on clinical aspects.

• Childhood Kidney Diseases
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• v.20 no.2
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• pp.45-49
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• 2016

Purpose: This study was performed to evaluate the effects of cyclosporine-A (CsA) on linear growth in pediatric patients with steroid-dependent (SDNS) or resistant nephrotic syndrome (SRNS). Methods: Thirty-five pediatric patients with SDNS or SRNS undergoing glucocorticoid (GC) and/or CsA treatment were retrospectively reviewed. Seventeen patients were treated with GC alone and 18 were treated with GC and CsA. The cumulative doses of GC and CsA were quantified (mg/kg/day). Linear growth during the follow-up period was defined as the difference in Z-score between the initial and final height according to the follow-up period (${\Delta}$ height Z score/year). The associations between linear growth and clinical parameters were analyzed. Results: The linear growth of patients in the two groups was not significantly different (P=0.262). The ${\Delta}$ height Z score/year did not show a significant correlation with the cumulative doses of CsA, but was negatively correlated with the cumulative dose of GC and positively correlated with the Z score for height at the time of diagnosis. Conclusion: In children with SDNS or SRNS undergoing GC therapy, added CsA treatment may not have harmful effects on linear growth.

• Childhood Kidney Diseases
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• v.9 no.2
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• pp.149-158
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• 2005

Purpose : To determine the histological findings and treatment outcome in cases of child hood nephrotic syndrome which required renal biopsy. Methods : We retrospectively reviewed the clinical, laboratory, pathologic findings and therapeutic outcomes of 159 nephrotic children who received a renal biopsy at the Department of Pediatrics, Kyunghee Medical University Hospital, Seoul from 1984 to 2004 over a period of 21 years. The renal biopsy was performed in nephrotic children who showed atypical features at presentation, or needed cytotoxic therapy because of frequent-relapsing, steroid-dependent, or steroid-resistant nephrotic syndrome(SRNS). Results : Minimal change disease(MCD) was found in 52.1$\%$ of the patients, followed by diffuse mesangial proliferation(33.1$\%$), focal segmental gomerulosclerosis(5.3$\%$), membranoproliferative glomerulonephritis(2.4$\%$), membranous nephropathy(2.4$\%$), and IgA nephropathy(1.8$\%$). In MCD children, 14.8$\%$ had hematuria, 22.7$\%$ had hypertension, 5.7$\%$ showed decreased renal function, and no patient was found to have an abnormal complement level. Among patients diagnosed with diseases other than MCD, 43.2$\%$ had hematuria, 21.0$\%$ was found to be hypertensive, 7.4$\%$ of children showed decreased renal function and only 3(3.7$\%$) had decreased complement level; the rates of hematuria and SRNS were found to be significantly higher than MCD patients. Among 37 SRNS patients, 30(81.0$\%$) showed a final remission state with long-term steroid therapy, including methylprednisolone pulse therapy, over 4 months, with or without cytotoxic therapy. Conclusion : Almost half of the cases of childhood nephrotic syndrome requiring renal biopsy were not diagnosed with MCD. Among atypical features, hematuria and steroid-resistance would be the most probable indicators for a diagnosis other than MCD. Even in patients with SRNS, long-term methylprednisolone pulse therapy may result in a good remission rate. (J Korean Soc Pediatr Nephrol 2005;9:149-158)