• Clinical and Experimental Pediatrics
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• v.59 no.5
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• pp.205-211
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• 2016

Idiopathic nephrotic syndrome (INS) in children is characterized by massive proteinuria and hypoalbuminemia. Minimal change nephrotic syndrome (MCNS) is the most common form of INS in children. The pathogenesis of MCNS still remains unclear, however, several hypotheses have been recently proposed. For several decades, MCNS has been considered a T-cell disorder, which causes the impairment of the glomerular filtration barrier with the release of different circulating factors. Increased levels of several cytokines are also suggested. Recently, a "two-hit" theory was proposed that included the induction of CD80 (B7-1) and regulatory T-cell (Treg) dysfunction, with or without impaired autoregulatory functions of the podocyte. In contrast to the well-established involvement of T cells, the role of B cells has not been clearly identified. However, B-cell biology has recently gained more attention, because rituximab (a monoclonal antibody directed against CD20-bearing cells) demonstrated a very good therapeutic response in the treatment of childhood and adult MCNS. Here, we discuss recent insights into the pathogenesis of MCNS in children.

• The Journal of Korean Medicine
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• v.21 no.1
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• pp.20-28
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• 2000

The purpose of this research is to investigate the synergistic effect of herb medicines with hydrocortisone and the regulation effect on the immune system of Onbitang and Dangguijakyaksan at the supernatant of PHA-P stimulated PBMC in the patients with minimal change nephrotic syndrome(MCNS). From the measurement of the concentration rate of IL-4, sCD23 and IL-13, the experiment yielded the following results : The Onbitang group showed a greater tendency to suppress IL-4 and IL-13 levels in MCNS group with no statistical significance. It showed very strong suppression in soluble CD23 compared with control group in MCNS group. The Dangguijakyaksan group, though not statistically significant, was inclined to suppress IL-4 level in MCNS group. It shows stronger suppression in sCD23 and IL-13 levels than these of control group in MCNS group. As for the synergistic effect, the group of hydrocortisone with herb medicines(Onbitang or Danguijakyaksan) produced more suppressive effect to IL-13 level in MCNS group than that of hydrocortisone-only group. They also tended to suppress sCD23 and IL-4 levels, though no statistical significance can be given. As to the suppressive effect of 1L-13 level, the group of Onbitang with hydrocortisone showed an increase of 22.6%, while the group of Dangguijakyaksan with hydrocortisone showed 14.7%. So Onbitang is more effective than Dangguijakyaksan. From the above results, a combinative treatment(herb medicines with hydrocortisone) can be an alternative method to substitute for steroid therapy. It can be a more effective therapy than steroid-only therapy because it is expected to reduce side effects and it shows more special effect to suppress IL-13 level. Based on the present results, further investigation concerning the serum IgE elevation is needed.

• Clinical and Experimental Pediatrics
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• v.54 no.8
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• pp.322-328
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• 2011

Nephrotic syndrome (NS) is one of the most common glomerular diseases that affect children. Renal histology reveals the presence of minimal change nephrotic syndrome (MCNS) in more than 80% of these patients. Most patients with MCNS have favorable outcomes without complications. However, a few of these children have lesions of focal segmental glomerulosclerosis, suffer from severe and prolonged proteinuria, and are at high risk for complications. Complications of NS are divided into two categories: disease-associated and drug-related complications. Disease-associated complications include infections (e.g., peritonitis, sepsis, cellulitis, and chicken pox), thromboembolism (e.g., venous thromboembolism and pulmonary embolism), hypovolemic crisis (e.g., abdominal pain, tachycardia, and hypotension), cardiovascular problems (e.g., hyperlipidemia), acute renal failure, anemia, and others (e.g., hypothyroidism, hypocalcemia, bone disease, and intussusception). The main pathomechanism of disease-associated complications originates from the large loss of plasma proteins in the urine of nephrotic children. The majority of children with MCNS who respond to treatment with corticosteroids or cytotoxic agents have smaller and milder complications than those with steroid-resistant NS. Corticosteroids, alkylating agents, cyclosporin A, and mycophenolate mofetil have often been used to treat NS, and these drugs have treatment-related complications. Early detection and appropriate treatment of these complications will improve outcomes for patients with NS.

• Childhood Kidney Diseases
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• v.5 no.2
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• pp.87-99
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• 2001

Purpose: We studied to find out apo-E genotype polymorphism in minimal change nephrotic syndrome(MCNS) and IgA nephropathy(IgAN) and to determine the relationship between apo-E genotype and clinical course of MCNS. Materials and Method: 43 MCNS patients and 15 IgAN patients were examined for apo-E polymorphism. 50 healthy blood donors were examined for apo-E genotype as control. Genomic DNA was prepared front peripheral blood leukocytes according to standard procedures. Results: As compared with control group, e4 allele frequency was significantly increased in MCNS (p<0.01). However, in IgAN e2 allele frequency, however, was 2.6 times higher than normal control (P<0.01). The frequency of e4 allele of frequent relapser group was 4.6 times higher than normal control and was 2 times higher than infrequent relapser group. Conclusion: We think that apo-E typing might be one of the parameters, which should be considered to predict the course of MCNS in children. MCNS with risky HLA profile and E4/4 genotype could indicate the need for a longer steroid administration. And apo-E genotype needs to be considered for the evaluation of therapeutic responses to other drugs. (J, Korean Soc Pediatr Nephrol 2001 ; 5 : 87-99)

• Childhood Kidney Diseases
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• v.3 no.1
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• pp.11-19
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• 1999

Purpose: MCNS is found in approximately $85\%$ of the idiopathic nephrotic syndrome in children and shows good prognosis with initial steroid therapy. MCNS most commonly appears between the ages of 2 and 10 yr. But the incidence and prognosis in adolescent MCNS are different from those found in young children; the prognosis and the response to therapy is unfavorable with increasing ages. So we compared the prevalence and the clinical manifestations of adolescent MCNS with that of childhood MCNS for management of adolescent MCNS. Methods: We conducted a retrospective study with a review of histopathologic findings and clinical manifestations of the 216 cases with MCNS which were divided into children group and adolescent group by their age of onset; under 12 years(childhood) and between 12-18 years(adolescent). Results: 1) The number of childhood idiopathic nephrotic syndrome was 245 cases, and that of adolescent idiopathic nephrotic syndrome was 55 cases. 188 cases($77\%$) showed MCNS, 30 cases($12\%$) FSGS, 4 cases($1.6\%$) MSPCN in childhood idiopathic nephrotic syndrome; 28 cases($51\%$) showed MCNS, 12 cases($22\%$) FSGS in adolescent idiopathic nephrotic syndrome. 2) The mean onset age was $7.53{\pm}5.5$ years, and the male to female ratio was 3.8:1 in childhood onset and 2.5:1 in adolescent onset with male predominance. 3) Hematuria was associated with $17\%$ of childhood onset and $39.3\%$ of adolescent onset disease(P=0.005). Hypertension appeared in $0.5\%\;and\;7\%$ in each group without significant difference between the groups. 4) 24 hour urine protein, SPI, albumin, BUN, cholesterol level showed no significant difference. 5) The response of childhood onset and adolescent onset MCNS to steroid therapy showed complete remission in $11.7\%\;&\;14.7\%$, infrequent relapsing in $29.2\%\;&\;28.5\%$, frequent relapsing in $23.9\%\;&\;14.7\%$, steroid dependent in $21.8\%\;&\;28.6\%$ each. Steroid resistant showed $13.3\%\;&\;14.7\%$ with no significance. 6) Immunosuppresant therapy was performed $57\%$ in childhood onset and $65\%$ in adolescent onset. 7) Mean number of relapse and duration from onset to first relapse showed no significance between two groups. Conclusion : Our results indicate that the incidence of hematuria, the rate of steroid dependent and frequent relapsing, and the recurrence rate were higher in adolescent MCNS; showed poorer steroid responsiveness and prognosis. Our data also point to the need for a more aggressive therapy to treat and make recommendations for the adolescent population as a whole.

• Childhood Kidney Diseases
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• v.22 no.1
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• pp.22-27
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• 2018

Purpose: Podocytes are important architectures that maintain the crucial roles of glomerular filtration barrier functions. Despite this structural importance, however, the mechanisms of the changes in podocytes that can be an important pathogenesis of minimal change nephrotic syndrome (MCNS) are not clear yet. The aim of this study was to investigate whether apoptosis is induced by interleukin (IL)-13 in cultured human podocytes. Methods: Human podocytes were treated with different IL-13 doses and apoptotic cells were analyzed using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL assay) and fluorescence-activated cell sorting (FACS). Results: The IL-13 increased the number of TUNEL-positive cells in a dose-dependent manner at 6 and 18 hours (P<0.05 and P<0.05, respectively). The apoptosis rate was appeared to be increased slightly in the IL-13-stimulated podocytes (8.63%, 13.02%, and 14.46%; 3, 10 and 30 ng/mL, respectively) than in the control cells (7.66%) at 12 hours by FACS assay. Conclusion: Our study revealed that IL-13 expression may increase podocyte apoptosis. Blocking the IL-13 signal pathway can potentially play an important role in regulating the apoptosis of podocytes.

• Childhood Kidney Diseases
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• v.11 no.1
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• pp.16-23
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• 2007

Purpose : Hypogammaglobulinemia has been observed in nephrotic syndrome, but its pathophysiology remains unknown. We evaluated the relationship between the serum IgG and at bumin levels for children with minimal change nephrotic syndrome(MCNS). Methods : The levels of immunoglobulin G(IgG), albumin and total cholesterol of a total of 46 children with MCNS(proteinuria $>40mg/m^2/h$, and serum albumin level <2.5g/dL were analyzed. Results : The mean values of albumin, IgG and total cholesterol in MCNS children were $1.7{\pm}0.3g/dL,\;368{\pm}143mg/dL\;and\;431{\pm}78mg/dL$, respectively. There was an inverse correlation between the albumin values and the total cholesterol values(r=0.68, P=0.0001), whereas there was a direct-proportional correlation between albumin values and the IgG values(r=0.4, P=0.01). Conclusion : The IgG level is associated with albumin level, and it may reflect the severity of urinary protein loss in MCNS. Further studies are needed to evaluate this phenomenon.

• Childhood Kidney Diseases
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• v.23 no.1
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• pp.1-6
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• 2019

Nephrotic syndrome (NS) is the most common glomerular disorder in childhood, and a vast majority of cases are idiopathic. The precise cause of this common childhood disease is not fully elucidated despite significant advancements in our understanding of podocyte biology. Idiopathic NS has been considered "a disorder of T-cell function" mediated by a circulating factor that alters podocyte function resulting in massive proteinuria since the last four decades. Several circulatory factors released from T-cells are considered to be involved in pathophysiology of NS; however, a single presumptive factor has not been defined yet. Extended evidence obtained by advances in the pathobiology of podocytes has implicated podocytes as critical regulator of glomerular protein filtration and podocytopathy. The candidate molecules as pathological mediators of steroid-dependent NS are CD80 (also known as B7-1), hemopexin, and angiopoietin-like 4. The "two-hit" hypothesis proposes that the expression of CD80 on podocytes and ineffective inhibition of podocyte CD80 due to regulatory T-cell dysfunction or impaired autoregulation by podocytes results in NS. Recent studies suggest that not only T cells but also other immune cells and podocytes are involved in the pathogenesis of MCNS.

• Childhood Kidney Diseases
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• v.9 no.2
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• pp.143-148
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• 2005

Purpose : Hypogammaglobulinemia has been observed in nephrotic syndrome, but its pathophysiology remains unknown. We evaluated serum immunoglobulins, IgG subclasses, and vaccine-induced viral antibodies(anti-hepatitis B surface IgG and anti-measles IgG) in children with minimal change nephrotic syndrome(MCNS). Methods : Using the stored sera, the levels of immunoglobulin(IgC, IgM, IgA, and IgC) and IgG subclasses(IgG 1, 2, ,3, and 4), anti-HBs Ab and anti-measles IgG of 21 children with MCNS were analyzed and compared to those of 25 age-matched healthy children. Results : The mean values of IgG and IgG1 were $390{\pm}187\;mg/dL$ and $287{\pm}120\;mg/dL$ in nephrotic children, and $1,025{\pm}284\;mg/dL$ and $785{\pm}19\;mg/dL$ in control children, respectively. The values of the total IgG and the 4 IgG subclasses in nephrotic children were all significantly depressed(P<0.001), but the IgM($251{\pm}183\;mg/dL\;vs. 153{\pm}55\;mg/dL$, P=0.02) and IgE values(P=0.01) were elevated, and the IgA values were not changed. The seropositivity of anti-HBs IgG was 42.9$\%$(9 of 21 cases) in the MCNS group and 52$\%$(13/25) in the control group, and that of anti-measles IgG was 75$\%$(16/21) and 92$\%$(23/25), respectively, but there was no statistical difference between the two groups. Conclusion : IgG and IgG subclass levels in MCNS children are all depressed without significant seronegativity of the vaccine-induced viral antibodies. Further studies are needed to resolve the cause of hypogammaglobulinemia in MCNS. (J Korean Soc Pediatr Nephrol 2005;9:143-148)

• Childhood Kidney Diseases
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• v.6 no.1
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• pp.48-55
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• 2002

Purpose: Thin glomerular basement membrane nephropathy (TGBMN) is recognized as the leading cause of microscopic hematuria in both children and adults. However thinning of glomerular basement membrane (TCBM) has been found in healthy adult and also is known to be associated with various renal diseases such as Alport syndronh, IgA nephropathy and mesangial proliferative glomerulonephritis. The association of TGBM with minimal change nephrotic syndrome (MCNS) has been very rare so that the present study was undertaken to determine the relationship between TGBM and MCNS. Methods: The study population consisted of 49 children with biopsy- proven MCNS who have been admitted to the pediatric department of Kyungpook University Hospital during the past 5 years from 1997 to 2001. Group I consisted of 8 children associated with TGBM and Group II 41 children without TCBM. Various parameters such as age of illness, duration from discovery of illness to the time of biopsy, family history of hematuria and other laboratory tests were compared between these two groups and the following results were obtained. Results: Age distribution showed slightly older age in Group I ($7.1{\pm}3.5$ years) compared to Group II ($4.8{\pm}2.9$ years). However this was not statistically different (P=0.056). Family history of hematuria was noted in 2 cases in Group II. Though statistically not significant, hematuria was seen in 2 out of 8 cases ($25\%$) in MCNS children with TGBM, compared to 7 out of 41 cases ($17\%$) with MCNS children without TGBM. Other parameters such as BUN, creatinine, 24 hours urine protein excretion, serum protein, albumin, cholesterol, and T4/T8 ratio, showed no difference. Also renal biopsy finding showed no significant difference and the thickness of glomerular basement membrane in Croup I was $188{\pm}30nm$. Conclusion: TGBM was found in 8 out of 49 children with MCNS ($16.3\%$). And this high frequency of occurrence indicates that these association is not an incidental findings. Typical clinical findings of TCBMN was not noted in all of the 8 children with MCNS associated with TGBM, suggesting that thinning of glomerular basement membrane (TCBN) is secondary to rather than the cause of MCNS. (J Korean Soc Pediatr Nephrol 2002;6: 48-55)