• Childhood Kidney Diseases
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• v.14 no.2
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• pp.143-153
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• 2010

Purpose: Recently, massive proteinuria has been observed in some transplant patients after switching cyclosporine A (CsA) to sirolimus. To evaluate the pathogenesis of sirolimus-associated proteinuria, we investigated the early changes in slit diaphragm molecules by various administrative conditions of sirolimus and CsA. Methods: In vitro-Mouse podocytes were incubated with buffer (C), sirolimus ($10\;{\mu}g/mL$) after CsA ($10\;{\mu}g/mL$) (C-S), sirolimus only (S) and CsA and sirolimus simultaneously (C+S) for 12, 24, and 48 hours. In vivo- twenty four SPF female Wistar rats were divided into 4 groups buffer (C), sirolimus after 2 weeks of CsA (C-S), sirolimus only (S) and CsA and sirolimus simultaneously (C+S). All groups were treated by intraperitoneal injection every other day for 4 weeks (CsA: 25 mg/kg, sirolimus: 0.5 mg/kg). The changes in mRNA of slit diaphragm molecules were examined by RT-PCR. Results: The mRNA of nephrin was significantly decreased in group C-S and C+S in vitro. In vivo, the mRNA of nephrin in all groups using sirolimus and the mRNA of podocin in group C-S and C+S were decreased. Microscopically, group C-S and C+S showed small vacuolization and calcification in proximal tubular epithelial cells. Immunohistochemistry using nephrin and podocin antibodies did not show remarkable decrease of staining along the glomerular capillaries. Electron-microscopically, focal fusion of foot processes was seen in group C-S and C+S. Conclusion: This study suggests the decrease of slit diaphragm molecules (nephrin and podocin) in podocyte may be one of the causes of sirolimus associated proteinuria, and podocyte injury by sirolimus may need a primary hit by CsA to develop the proteinuria.

• Neonatal Medicine
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• v.17 no.1
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• pp.75-83
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• 2010

Purpose : This study was performed to determine the predictors of failed closure of a patent ductus arteriosus (PDA) following the first course of indomethacin in symptomatic preterm infants. Methods : Forty three of 43 preterm infants, admitted to the neonatal intensive care unit diagnosed with PDA and treated with indomethacin at the Korea University Medical Center between January 1990 and October 2007, ware studied. The perinatal risk factors affecting the failed closure of PDA were retrospectively assessed. Results : The failed PDA closure group included 16 (37%) out of 43 infants three of whom underwent surgery. The closure group included 27 (63%) out of 43 infants. In the failed closure group, the Apgar scores (1 min, 5 min) were significantly higher (P<0.05) and antenatal steroid administration was significantly lower (P<0.05). In addition, dopamine administration was significantly lower (P<0.05) and the mean postnatal age at diagnosis was significantly lower (P<0.05). Multiple logistic regression for the prediction of failed PDA closure found only antenatal steroid administration (OR 0.092, CI 0,010-0.826, P=0.0331) as an associated factor. Conclusion : In patients with antenatal steroid administration the failed PDA closure rate was significantly lower. Therefore, antenatal steroid administration can be considered as an important factor for the closure of PDA in preterm pregnancies.

• Clinical and Experimental Pediatrics
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• v.49 no.2
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• pp.192-197
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• 2006

Purpose : Vascular endothelial growth factor(VEGF) is a key cytokine for controlling vascular permeability and angiogenesis, which is one of the major findings in airway remodeling. However, it is not well known if it is associated with acute lower respiratory tract disease such as lobar pneumonia. The aim of this study is to compare serum VEGF levels in patients with asthma according to its severity and duration of cough, and to compare its levels with children with lobar pneumonia. Methods : Using a sandwich enzyme-linked immunosorbent assay, the serum VEGF levels were measured in 16 mild asthmatics, 14 moderate to severe asthmatics, six children with lobar pneumonia, and 22 control subjects. The asthmatics were also classified into three groups according to the duration of cough. Serum VEGF levels were compared in each group. Results : Serum VEGF levels were significantly increased in the children with moderate to severe asthma and lobar pneumonia compared to the children with mild asthma and control subjects. Serum VEGF levels were higher in children with chronic coughs of more than two weeks than in children with coughs lasting less than two weeks. Serum levels of VEGF showed positive correlations with blood platelet and white blood cell counts. Conclusion : VEGF increased according to the severity of asthma and duration of cough in children with asthma. It may play an important role not only in chronic airway inflammation, but also in the acute inflammation in children with lower respiratory tract disease.

• Clinical and Experimental Pediatrics
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• v.49 no.7
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• pp.737-744
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• 2006

Purpose : To assess the usefulness of $^{99m}Tc-DISIDA$ scanning in the early evaluation of neonatal cholestasis and to verify the diagnostic value of this test in the differential diagnosis of biliary atresia. Methods : DISIDA scannings were performed and analyzed in 87 children(58 males and 29 females; age, 18-139 days, mean, 59.1 days) with neonatal cholestasis. Five groups according to the final diagnosis and the results of DISIDA scanning were analyzed by scatter plots using the parameters of age and the level of liver function tests(direct bilirubin, AST, ALT, ALP, GGT). The diagnostic sensitivity, specificity and accuracy of DISIDA scanning in the diagnosis of biliary atresia were compared between a higher bilirubin group and a lower bilirubin group(direct bilirubin level >5 mg/dL vs. <5 mg/dL) decided by the pattern of scatter plots. Results : DISIDA scannings in the diagnosis of biliary atresia were analyzed by high sensitivity(100 percent, 16/16) but lower specificity(70.4 percent, 50/71) and accuracy(75.9 percent, 66/87). False positivity(29.6 percent, 21/71) was higher in patients with a higher direct bilirubin level(42.5 percent for >5 mg/dL vs. 9.7 percent for <5 mg/dL, P<0.01). The age and the level of liver function tests(AST, ALT, ALP, GGT) analyzed by scatter plots revealed neither diagnostic value in predicting final diagnosis nor estimated the accuracy rate of DISIDA scanning in the evaluation of neonatal cholestasis. Conclusion : We suggest that DISIDA scannings should not be routinely used in evaluating neonatal cholestasis with elevated direct bilirubin level(>5 mg/dL), especially if it delays early diagnosis and surgical intervention.

• Childhood Kidney Diseases
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• v.7 no.2
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• pp.150-156
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• 2003

Purpose : Efforts to predict the clinicopathological outcome of IgA nephropathy have been made but have yielded conflicting results and have not helped in deciding the appropriate timing of the renal biopsy. In this study, we reviewed the predictive factors of clinicopathological outcome for finding out the criteria of renal biopsy timing of IgA nephropathy. Methods : Forty children diagnosed with biopsy proven IgA nephropathy at Wonju Christian Hospital were studied retrospectively, based on medical records. Results : Among 39 patients, 2 children progressed to higher serum creatinine level. One of them reached to the end stage renal disease within 2 year 7 months. According to WHO histopathological classification, there were 15 cases of class I, 14 cases of class II, 7 cases of class III, and 3 cases of class IV. In the mild histological classes(class I, II), gross hematuria was shown in 23 out of 29 children(P=0.02). In the severe histological classes(class III, IV), gross hematuria was noted in 4 out of 10(P>0.05). The tubulointerstitial changes were grade 1 in 24 cases, grade 2 in 4 cases, grade 3 in 8 cases, and grade 4 in 3 cases. With an increase in the tubulointerstitial grade, the 24 hour urine protein/albumin ratio increased. Serum creatinine less than 0.79 mg/dL could predict the lower grade(grade 1 and 2) of tubulointerstitial changes. But serum creatinine greater than 1.13 mg/dL could predict the higher grade(grade 3 and 4) of tubulointerstitial changes. In children with gross hematuria(n=27), serum creatinine was lower(0.78 vs 1.09 mg/dL, P=0.027), serum IgA was higher(316.3 vs 198.8 mg/dL), and the cases of lower WHO classification(I and II) were more common(23 vs 4, P=0.029) than the children with microscopic hematuria. Conclusion : Serum creatinine less than 0.79 mg/dL, macroscopic hematuria, and higher 24 hour urine protein/albumin ratio would predict the lower grade glomerulo tubulointerstitial lesion in IgA nephropathy and could be used as the criteria delaying the renal biopsy.

• Childhood Kidney Diseases
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• v.5 no.2
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• pp.117-124
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• 2001

Purpose : Since Mendoza(1990)'s report that long term methylprednisolone pulse therapy by Mendoza protocol (MP therapy) is a good treatment option in focal segmental glomerulosclerosis(FSGS), there have been reports of the effects of this therapy in steroid-resistant nephrotic syndrome. However, no studies have been performed on the effects of MP therapy in steroid- dependent nephrotic syndrome and secondary nephrotic syndrome. In this study, we investigated the effects of long term MP therapy in primary and secondary nephrotic syndrome in which previous treatment options were not effective. Methods : We chose 10 children who were diagnosed with steroid-dependent minimal change nephrotic syndrome(SD-MCNS), who had shown frequent relapse during the immunocompromised or cytotoxic therapy Period, and 6 children with FSGS and 5 children with secondary nephrotic syndrome children, who had shown no response during the previous therapy period. We treated these patients according to Mendoza protocol involving infusions of high doses of methylprednisolone, often in combination with oral cyclophosphamide for 82 weeks. Results : In all the 10 children with SD-MCNS, complete remission was visible on average of $18{\pm}9$ days after MP therapy was started. However, all these children relapsed during or after MP therapy. In these children, the mean relapse rate prior to MP therapy was $2.1{\pm}1.0$ relpases/year, which was reduced to $1.4{\pm}0.9$ relapses/year during MP therapy(P>0.05) and rose to $2.7{\pm}1.0$ relapse/year after MP therapy. Of the 6 children with FSGS, 4 children($67\%$) showed complete remission, of whom 3 children($50\%$) remained in the remission status during the follow up period, $1.2{\pm}0.7$ years, after the end of MP therapy. 2 children($33\%$) showed no response. All of the 5 children with secondary nephrotic syndrome showed remission and remained in the remissiom status during the follow up period, $1.7{\pm}0.6$ years The only side effect of MP therapy was transient hypertension in 10 children of ail subjects during the intravenous infusion of methylprednisolone. Conclusion : We conclude that although long term MP therapy is not effective in the treatment of SD-MCNS, it is an effective therapy against intractable FSGS and secondary nephrotic syndrome. (J Korean Soc Pediatr Nephrol 2001 ; 5 : 117-24)

• Childhood Kidney Diseases
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• v.3 no.2
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• pp.161-169
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• 1999

Purpose : The urinary mass screening program for the detection of proteinuria in school aged population has been performed in Seoul since 1981. Systematic evaluation in corporation with the Seoul School Health Center for students with proteinuria identified in the mass screening has been performed from 1987. The results of urinary mass screening up to 1994 was reported. I report here the results of urinary mass screening from 1995 to 1997 and compare them with previous results and attempt to reveal the significance of urinary mass screening. Objects and Methods : In the 3-year period between 1995 and 1997, annually about 460,000 students comprising 3 different age groups; 5th grade of elementary school, 2nd grade of middle school and 2nd grade of high school were chosen, corresponding to the approximate ages of 11, 14, and 17 years, respectively. These subjects accounted for 26% of total school aged children in Seoul. The screening program was carried out in 3 steps. The 1st test was performed with dipstick at school and the 2nd at the Seoul School Health Center. Those students who showed proteinuria in the 1st and 2nd tests were referred to the hospital. Laboratory examinations including renal biopsies were performed to those students with pathologic proteinuria to clarify the incipient renal diseases. Results : 1) The prevalence of asymptomatic proteinuria was 0.28% in the 1st test. It peaked at the group of 14 years old as 0.34%, compared with 0.26% at the group of 11 years old and 0.24% at the group of 17 years old. It reached to 0.26% in male and 0.30% in female. 2) 25 percent of those having proteinuria at the first test were positive at the second test. 3) The proportion of patients with proteinuria by 3rd test were as follows; 25% of transient proteinuria, 55% of orthostatic proteinuria, 6% of constant proteinuria, 12% of proteinuria with hematuria, and 2% of transient proteinuria with isolated hematuria. Pathologic proteinuria were totaled as 20%. The prevalence of renal diseases among the age group of 7-18 years old was estimated to be 1.4 per 10,000. 4) Renal biopsy performed on 38 children with proteinuria at the third test revealed IgA nephropathy in 17(44%), focal segmental glomerusclerosis in 5(13%), minimal change disease in 4(11%), membranoproliferative glomeronephritis in 3(8%), $Henoch-Sch\"{o}nlein$ purpura nephritis in 3(8%), and others in 6(16%). Therefore, the prevalence of IgA nephropathy among the age group of 7-18 years old was estimated to be 0.64 per 10,000. 5) The prevalence of chronic renal failure was estimated to be 5.7 per 1 million of 7 to 18 years age group. Conclusions : 1) The prevalence of proteinuria in the first screening test was 0.28% and finally only 5% of them showed the pathologic proteinuria at the third test. 2) The prevalence of IgA nephropathy and chronic renal failure were 0.63 per 10,000 and 5.7 per 1 million, respectively among school-aged children in Seoul.

• Clinical and Experimental Pediatrics
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• v.46 no.1
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• pp.76-82
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• 2003

Purpose : The aim of this study was to determine whether differences exist in the presentation, clinical course, and outcome of Graves' disease between prepubertal children and adolescents. Methods : A retrospective chart review of 14 prepubertal(PREPUB, $7.2{\pm}0.9yr) and 38 pubertal (PUB, $12.4{\pm}1.5yr$) children with Graves' disease between January 1989 and November 1995 at St. Mary's Hospital and Kangnam St. Mary's Hospital was undertaken. Results : There were no significant differences in $T_3$, $T_4$, TSH between two the groups at diagnosis. The PUB group had significantly higher titers of antimicrosomal antibody(positive dilution factor $11,727.3{\pm}22,888.4$) than did the PREPUB group($2,111.5{\pm}2,285.0$, P<0.001). The PREPUB group had significantly higher titers of TSH-binding inhibitory immunoglobulin(TBII, $62.5{\pm}39.6$) than did the PUB group($44.9{\pm}10.4$, P<0.05) before treatment started. The duration(months) of medical therapy before thyroid function tests were normalized was longer in the PREPUB group than in the PUB group($T_3:6.8{\pm}5.0$ vs. $5.4{\pm}13.2$, $T_4:2.3{\pm}1.9$ vs. $2.1{\pm}2.2$, $TBII:26.7{\pm}24.0$ vs. $20.8{\pm}12.1$), especially that of TSH was significantly longer in the PREPUB group($14.6{\pm}11.0$ vs. $6.8{\pm}7.8$, P< 0.05). Total length of medical therapy was significantly longer in the PREPUB group than the PUB group($52.3{\pm}19.3$ vs. $37.9{\pm}16.3months$, P<0.01). During three years of antithyroid drug therapy, in the PREPUB group, the remission rate was lower and the relapse rate was higher than in the PUB group. Total length of treatment correlated negatively with chronological age(P=0.03). Conclusion : Prepubertal children require longer medical therapy to achieve a remission than do pubertal children. But there is an obvious need for more studies because of the small number of patients and the short duration of the follow-up.