• Clinical and Experimental Pediatrics
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• v.58 no.10
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• pp.402-405
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• 2015

IgA nephropathy usually presents as asymptomatic microscopic hematuria or proteinuria or episodic gross hematuria after upper respiratory infection. It is an uncommon cause of end-stage renal failure in childhood. Pulmonary hemorrhage associated with IgA nephropathy is an unusual life-threatening manifestation in pediatric patients and is usually treated with aggressive immunosuppression. Pulmonary hemorrhage and renal failure usually occur concurrently, and the pulmonary manifestation is believed to be caused by the same immune process. We present the case of a 14-year-old patient with IgA nephropathy who had already progressed to end-stage renal failure in spite of immunosuppression and presented with pulmonary hemorrhage during oral prednisone treatment. His lung disease was comparable to diffuse alveolar hemorrhage and was successfully treated with plasmapheresis followed by oral prednisone. This case suggests that pulmonary hemorrhage may develop independently of renal manifestation, and that plasmapheresis should be considered as adjunctive therapy to immunosuppressive medication for treating IgA nephropathy with pulmonary hemorrhage.

• Childhood Kidney Diseases
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• v.13 no.2
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• pp.153-160
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• 2009

Purpose : The intestinal mucosal defect has been known as one of the pathogenicmechanisms of IgA nephropathy. Oral antigens usually induce the activation of Th2 cells and mast cells. These cells secrete cytokines IL-4, IL-5 and TGF-$\beta$, which increase IgA production. Although ketotifen (benzocycloheptathiophene) is an H1 antagonist and a mast cell membrane stabilizer, it could protect the gastrointestinal membrane through inhibiting the production of IL-4, IL-5, PGE2, and LTB4, and decreasing the activity of nitric oxide synthease. Therefore, we have investigated if ketotifen may protect the development of IgA nephropathy with an oral antigen. Methods : ICR mice were used as an animal model orally with Poliovax only [ketotifen (-)], the other group was given oral ketotifen [ketotifen (+)] in addition to Poliovax. Results : Mesangial IgA deposition developed in 11 out of the 18 mice in the ketotifen (-) group, while in three out of the nine mice in ketotifen (+) group. The mesangial change developed in 16 out of the 18 mice in the ketotifen (-) group, while in five out of the nine mice in the ketotifen (+) group. Serum IL-4 and IL-5 levels were not significantly lower in the latter group than in the former. Conclusion : According to the statistical results from the above, ketotifen therapy would be beneficial to reducing mesangial changes in IgA nephropathy.

• Clinical and Experimental Pediatrics
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• v.50 no.2
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• pp.170-177
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• 2007

Purpose : Clinicopathological features were investigated to clarify the outcome and prognostic indicators for patients with IgA nephropathy in Korean children. Methods : We reviewed the outcomes of 61 patients in whom IgA nephropathy was diagnosed before the age of 15 years from 1991 to 2005 and followed-up at least for one year. All patients were confirmed by renal biopsy. Results : After mean follow-up of 5.2 years from onset, 24 patients of 61 (39.3%) were in clinical remission at the last examination. Thirty patients (49.2%) had hematuria or mild proteinuria (<$1g/m^2/d$), five (8.2%) had severe proteinuria (${\geq}1g/m^2/d$), and two (3.3%) had chronic renal failure. By univariate analysis, initial presentation at onset and Haas classification were less concordant with outcome. Hypertension during follow-up, rather than hypertension at presentation, was significantly correlated with outcomes (P<0.01). Sixty percent of patients who had more than 20% of glomerular sclerosis or crescent progressed to severe proteinuria or chronic renal failure, as compared with 7.1% of those who did not (P<0.01). Conclusion : Prognosis of childhood IgA nephropathy had a relatively benign course during a mean follow-up of 5.2 years. Persistent hypertension during follow-up and more than 20% of glomerular sclerosis or crescent were strong predictors of a progressive course of IgA nephropathy. A new histologic classification according to characteristics of childhood IgA nephropathy must be established to assess prognosis. Further efforts should be made to understand the prognosis of IgA nephropathy through long-term follow-up.

• Korean Journal of Acupuncture
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• v.24 no.4
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• pp.163-180
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• 2007

Objective : Oriental medicines have been applied to Membranous nephropathy(MN) for the purpose on increasing renal blood flow and modulating immune activity in according to Oriental medicine theories. Magsungsinyeom-bang (MSSYB) is one of the prescription which is known to show positive results in clinic with lack of laboratorial evidence. Thus, this study was aimed to evaluate the effects of MSSYB and partially investigate the mechanisms of it. Methods : The effect of MSSYB was evaluated by the morphology for the GBM thickening, protein excretion in urine and biochemical parameters in serum using cBSA-induced MN mice model. Mice were administered with MSSYB(250 or 500 mg/kg) or PBS for control group from experimental week 3 for 4 weeks. Results : 24 hrs proteinuria and the concentrations BUN was significantly decreased in the MS groups compared to the control group while the concentrations of serum albumin was higher in the MS groups than control group. MSSYB didn't affect the ratio of CD3e+/CD or 19CD4+/CD8 in the spleen and kidney, but inhibit the expression of IL-1${\beta}$, TNF-${\alpha}$, IL-6, and production of IgG and IgM. In histological analysis of kidney tissue, thickening of GBM was significantly decreased in the MS group compared to control group. Conclusions : MSSYB showed the positive results on the cBSA-induced membranous nephropathy in mice, thus, it could be a useful candidate for oriental drug for treating the membranous nephropathy in clinic.

• The Journal of Korean Medicine
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• v.30 no.5
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• pp.61-76
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• 2009

Background: Membranous nephropathy (MN) is the most common cause of adult nephrotic syndrome worldwide and has been defined as granular subepithelial deposition of immune complexes along the glomerular basement membrane (GBM). MN has few known treatments and gives rise to side effects under treatment with steroids and immunosuppressives. Objective: The purpose of this experimental study was to demonstrate the effects of Scutellariae Radix extract (SRE) treatment on MN mouse model induced by cBSA. Methods: We divided mice into 4 groups. The Normal group had no treatment. We induced MN mouse model to the other 3 groups by injecting cBSA into the abdominal cavity. The control group was treated with cBSA (10 mg/kg, i.p.) only. The second group, 'SRE-250', was treated with cBSA (10 mg/kg, i.p.) and SRE (250 mg/kg, p.o.). The third group, 'SRE-500', was treated with cBSA (10 mg/kg, i.p.) and SRE (500 mg/kg, p.o.). After cBSA and SRE treatment for 4 weeks, gain in body weight, 24hrs proteinuria, serum albumin, total cholesterol, triglyceride, BUN and creatinine of all groups were measured. TNF-$\alpha$, IL-6, IL-1$\beta$, IL-10, IFN-$\gamma$, IgA, IgM and IgG levels of all groups were gauged. H&E staining and electron microscopy of the kidney were observed. Results: SRE showed significant decrease in the 24hrs proteinuria, serum triglyceride, BUN, TNF-$\alpha$, IL-6, serum IgA, IgM and IgG levels compared with the control group. SRE showed increase in the serum IL-10 and IFN-$\gamma$ levels compared with control on RT-PCR. SRE considerably decreased in the thickening of the GBM on H&E staining and deposition of electron-density on electron microscopy of the kidney compared with the control. Conclusions: According to the above results, it is suggested that SRE decreases the symptoms of MN induced by cBSA in mouse model. Therefore, SRE seems to be applicable to MN in clinical practice.

• Clinical and Experimental Pediatrics
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• v.53 no.4
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• pp.548-553
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• 2010

Purpose : IgA nephropathy (IgAN) is the most commonly occurring form of chronic glomerulonephritis in pediatric cases. Human leukocyte antigen (HLA) genes have been implicated in various inflammatory and autoimmune diseases. The present study was conducted to investigate the association between 2 single nucleotide polymorphisms (SNPs) of the HLA-G gene and childhood IgAN. Methods : The authors analyzed and compared $HLA-G$ gene SNPs (rs1736936 and rs2735022) in 174 patients with childhood IgAN and in 438 healthy controls. In addition, IgAN patients were dichotomized and compared with respect to proteinuria (< and >$4mg/m^2/hour$), the presence or absence of podocyte foot process effacement, and the presence of pathologically early and advanced disease markers such as interstitial fibrosis, tubular atrophy, or global sclerosis. Results : No significant SNP frequency differences were observed for the $HLA-G$ gene between IgAN patients and the control group. Moreover, no significantly associated SNP was observed with the presence of proteinuria, podocyte foot process effacement, or pathologically advanced markers. However, the haplotype, composed of rs1736936 and rs2735022, showed a significant association with the susceptibility to develop childhood IgAN (haplotype T/C: dominant model, $P$=0.049; haplotype C/T: recessive model, $P$=0.030). Conclusion : Our results indicate that rs1736936 and rs2735022 as the $HLA-G$ gene promoter haplotype might be associated with the susceptibility to develop childhood IgAN in the Korean population.

• The Journal of Korean Medicine
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• v.30 no.2
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• pp.63-78
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• 2009

Objective: The purpose of experimental study was to prove the effects of Boyangmakseong-bang (BYMSB) treatment on cBSA-induced in a MN mouse model. Methods: We divided mice into 4 groups. The Normal group had no treatment. We used cBSA and induced MN mouse model to the other 3 groups. The Control group was treated with cBSA (9mg/kg i.p) only. The second group, named 'BY-250', was treated with cBSA (9mg/kg i.p) and BYMSB extract (250mg/kg, p.o). The third group, named 'BY-500', was treated with cBSA (9mg/kg i.p) and BYMSB extract (500mg/kg, p.o). After cBSA and BYMSB extract treatment for 4 weeks, the increase in percentage of body weight, proteinuria, serum albumin, total cholesterol, creatinine and BUN of all groups were measured. The CD3+, CD19+, CD4+, CD8+ cell levels of spleen of all groups were analyzed. IgA, IgG, IgM, IL-$1{\beta}$, TNF-${\alpha}$, IL-6 and IFN-${\gamma}$ levels of all groups were gauged. H&E staining, immunofluorescence staining and electron microscopy of kidney were observed. Results: BYMSB showed significant decrease in the 24hrs proteinuria, serum total cholesterol, serum IgG levels and BUN levels, and showed significant increase in the serum albumin levels compared with the control group. BYMSB showed increase in the increasing percentage of body weight and IFN-${\gamma}$ levels compared with the control. BYMSB showed decrease in the CD3+ T cells, CD4+ Th cells, IL-$1{\beta}$, TNF-${\alpha}$ and IL-6 levels, but did not show significant change compared with the control. BYMSB showed considerable decrease in the thickening of the GBM on H&E staining, deposition of IgG on immunofluorescence staining and deposition of electron-density on electron microscopy of kidney compared with the control. Conclusions: According to the above results, it is suggested that BYMSB decreases the symptoms of MN induced by cBSA in a mouse model. Therefore BYMSB seems to be applicable to MN in clinical practice.

• Clinical and Experimental Pediatrics
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• v.50 no.4
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• pp.369-375
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• 2007

Purpose : There have been numerous researches on urine ${\beta}_2$-microglobulin (${\beta}_2$-M) concerned with primary nephrotic syndrome and other glomerular diseases, but not much has been done in relation to pediatric age groups. Thus, our hospital decided to study the relations between the analysis of the test results we have conducted on pediatric patients and renal functions. Methods : Retrospective data analysis was done to 102 patients of ages 0 to 4 with renal diseases with symptoms such as hematuria, edema, and proteinuria who were admitted to Chung-Ang Yongsan Hospital and who participated in 24-hour urine and urine ${\beta}_2$-M excretion test between January of 2003 and January of 2006. Each disease was differentiated as independent variables, and the statistical difference of the results of urine ${\beta}_2$-M excretion of several groups of renal diseases was analyzed with student T-test by using test results as dependent variables. Results : Levels of urine ${\beta}_2$-M excretion of the 102 patients were as follows : 52 had primary nephrotic syndrome [MCNS (n=45, $72{\pm}45{\mu}g/g$ creatinine, ${\mu}g/g-Cr$), MPGN (n=3, $154{\pm}415{\mu}g/g-Cr$), FSGS (n=4, $188{\pm}46{\mu}g/-Cr$], six had APSGN ($93{\pm}404{\mu}g/g-Cr$), seven had IgA nephropathy ($3,414{\pm}106{\mu}g/g-Cr$), 9 had APN ($742{\pm}160{\mu}g/g-Cr$), 16 had cystitis ($179{\pm}168{\mu}g/g-Cr$), and 12 had HSP nephritis ($109{\pm}898{\mu}g/g-Cr$). IgA nephropathy (P<0.05) and APN (P<0.05) were significantly higher than in other renal diseases. Among primary nephrotic syndrome, FSGS with higher results of ${\beta}_2$-microglobulin test had longer treatment period (P<0.01) when compared to the lower groups, but no significant differences in Ccr, BUN, or Cr were observed. Conclusion : IgA nephropathy and APN groups showed significantly higher level of ${\beta}_2$-M excretion value than other groups. Although ${\beta}_2$-microglobulin value is not appropriate as an indicator of general renal function and pathology, it seems to be sufficient in the differential diagnosis of the UTI and in the prediction of the treat-ment period of nephrotic syndrome patients.

• Clinical and Experimental Pediatrics
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• v.53 no.2
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• pp.215-221
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• 2010

Purpose : Interleukin-17 (IL-17) is produced by activated CD4+T cells and exhibits pleiotropic biological activity on various cell types. IL-17 was reported to be involved in the immunoregulatory response in IgA nephropathy (IgAN). Our aim was to investigate the association between single-nucleotide polymorphisms (SNPs) in IL-17 receptor A (IL-17RA) gene and childhood IgAN. Methods : We analyzed the SNPs in the IL-17RA in 156 children with biopsy-proven IgAN and 245 healthy controls. We divided the IgAN patients into 2 groups and compared them with respect to proteinuria (${\leq}4$ and >$4mg/m^2/h$, ${\leq}40$ and >$40mg/m^2/h$, respectively) and the presence of pathological levels of biomarkers of diseases such as interstitial fibrosis, tubular atrophy, or global sclerosis. Results : No difference was observed between the SNP genotypes rs2895332, rs1468488, and rs4819553 between IgAN patients and control subjects. In addition, no significant difference was observed between allele frequency of SNPs rs2895 332, rs1468488, and rs4819553 between patients in the early and advanced stage of the disease. However, significant difference was observed between the genotype of SNP rs2895332 between patients with proteinuria (>$4mg/m^2/h$) and those without proteinuria (codominant model OR 0.36, 95% CI 0.19-.66, P <0.001; dominant model OR 0.35, 95% CI 0.17-.69 P =0.002; recessive model OR 0.12, 95% CI 0.01-.06 P =0.025). Conclusion : Our results indicate that the SNP in IL-17RA (rs2895332) may be related to the development of proteinuria in IgAN patients.

• Clinical and Experimental Pediatrics
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• v.50 no.1
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• pp.28-32
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• 2007

Purpose : Human angiotensin converting enzyme (ACE) gene shows an insertion/deletion polymorphism in 16 intron, and three genotypes are determined by whether a 287 bp fragment of the DNA is present or not; II, ID and DD genotype. DD genotype has been suggested as a risk factor of chronic nephrotic disease such as IgA nephropathy and diabetic nephropathy, various cardiovascular diseases and several other diseases. ACE activity increases in acute hepatitis, chronic persistent hepatitis, chronic active hepatitis and cirrhosis. On the other hand, patients with fatty livers have normal ACE activity. This study was designed to find out the relation between polymorphsims of the ACE genes and neonatal hyperbilirubinemia in Koreans. Methods : The genomic DNA was isolated from 110 full-term Korean neonates who had hyperbilirubinemia with no obvious causes (serum bilirubin$${\geq_-}12mg/dL$$) and 164 neonates of a control population (serum bilirubin <12 mg/dL). We performed polymerase chain reaction (PCR) to see the allele of the ACE gene. Electrophoresis was done in the PCR products in 1.5 percent agarose gel, and then DNA patterns were directly visualized under ethidium bromide staining. Results : ACE genotypes in the hyperbilirubinemia group are as follows; 26.36 percent for II, 53.64 percent for ID, 20.00 percent for DD, 0.532 for I allele and 0.468 for D allele. These distributions were not significantly different from those in the control group; 24.39 percent for II, 51.83 percent for DI, 23.78 percent for DD, 0.503 for I allele and 0.497 for D allele. Conclusion : In this study, ACE gene polymorphism was detected in the neonatal hyperbilirubinemia and control group. The most frequent genotype was ID. Our results indicate that the ACE gene polymorphism is not associated with the prevalence of neonatal hyperbilirubinemia in Koreans.