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The Changes of Slit Diaphragm Molecules After Using Sirolimus (Sirolimus 사용 후 사구체 기저막 세극막 관련 분자의 변화)

  • Choi, Jung-Youn;Han, Gi-Dong;Kim, Yong-Jin;Park, Yong-Hoon
    • 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.

Clinical Features of Enuresis in Children with Diabetes Mellitus (소아 당뇨병 환아에서 야뇨증의 임상적 특징)

  • Kim, Myoung-Uk;Kim, Sae-Yoon;Choi, Jung-Youn;Cho, Min-Hyun;Ko, Cheol-Woo;Kim, Heung-Sik;Park, Yong-Hoon
    • Childhood Kidney Diseases
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    • v.14 no.2
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    • pp.210-217
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    • 2010
  • Purpose : Diabetes mellitus (DM) is known as one of the common causes of secondary enuresis in children. However, enuresis in diabetic children is overlooked only as a symptom of polyuria due to hyperglycemia. We evaluated the prevalence of nocturnal enuresis in children with diabetes mellitus in this paper. Methods : Among children with diabetes in three hospitals in Daegu area, 117 agreed to 'Tele research by means of a questionnaire'. Results : Diabetic patients were divided into two groups: Nocturnal enuresis and nonnocturnal enuresis group. thirty-two of 117 (27.0%) patients were in enuresis group, with more daytime urination than non-nocturnal enuresis group ($4.2{\pm}1.6/3.6{\pm}1.2$ times, P=0.016). HbA1c at diagnosis was $12.0{\pm}2.3%/12.0{\pm}2.5%$, and at follow-up $9.3{\pm}2.3%/8.3{\pm}2.3%$ (P =0.042). Insulin was administered at $1.1{\pm}0.5/1.1{\pm}0.4$ units/kg/day. Ten children of enuresis (31.2%) group were monosymptomatic (MNE) and 22 (68.8%) children were non-monosymptomatic enuresis (non-MNE). Fourteen (43.8%) of enuresis group had persistent symptoms, with 5 MNE and 9 non-MNE each. HbA1c at diagnosis was $11.1{\pm}2.5$, $12.4{\pm}2.1$, higher in non-MNE (P=0.144). Average arousal during sleep was step $3.3{\pm}1.2$, $2.5{\pm}1.0$, higher in improved enuresis group (P=0.059). Conclusion : Nocturnal enuresis among DM patients is underestimated. However, considering psychological and social effects of enuresis in children, extensive and long-term studies are needed in the future to clarify relationship between prevalence and DM control.

Breakthrough Urinary Tract Infection: A Clinical Study of Experience of a Single Center (예방적 항생제 사용중에 발생한 요로감염: 단일 병원에서 경험한 임상연구)

  • Bae, Sang-In;Cheon, Chong-Kun;Kim, Su-Young
    • Childhood Kidney Diseases
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    • v.14 no.2
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    • pp.203-209
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    • 2010
  • Purpose : It has been a common medical practice to use prophylactic antibiotics to prevent recurrent urinary tract infections (UTI) in high risk situations such as urinary tract obstruction, vesicoureteral reflux, neurogenic bladder, or urinary stones. But sometimes, we meet difficult situation of breakthrough infections (BI) which might cause new or progressive renal scarring. The clinical characteristics of children contracting breakthrough UTI experienced in a single center were studied. Methods : The study was done retrospectively through medical records of 150 pediatric patients who had been cared in pediatric and urologic clinics of Pusan National University Hospital from Jan. 2001 till June 2006 and had prophylactic antibiotics to prevent recurrent UTI. Results : The starting age of prophylactic antibiotics of 150 patient was 1-76 months, and median age was 5 months. The BI developed 61 times in 43 patients (28.7%), 1.5 times per 100 patient-months. The BI occurred more frequently in patients with higher grade of VUR, and in the cases with abnormal DMSA scan. Co-trimoxazole was more effective than 2nd and 3rd generation cephalosporins to prevent UTI. The distribution of causative organisms was more diverse than usual UTI. The causative organisms were sensitive to the antibiotics used for prophylaxis in 29.5%, and resistant in 59.1%. After experience of BI, 40 percents of patients went to the surgical treatment including endoscopic injection of Deflux, 35% to new antibiotics for prophylaxis, 26% remain on the same antibiotics as the previous one. Conclusion : Based on our study results, preexisting renal scar might be one of the factors which should be considered in favor of early surgical interventions of VUR. Poor compliance and wrong selection of antibiotics such as cephalosporins are important underlying causes of breakthrough UTIs.

Incidence of Febrile Urinary Tract Infection According to Clinical Characteristics in Patients with Congenital Hydronephrosis and Hydronephrotic Patients Diagnosed at First Febrile Urinary Tract Infection (선천성 수신증 환자군과 첫 발열성 요로감염으로 진단 시 발견된 수신증 환자군에서 임상적 특징에 따른 발열성 요로감염의 발생률)

  • Kim, Geun-Jung;Rhie, Seon-Kyeong;Lee, Jun-Ho
    • Childhood Kidney Diseases
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    • v.14 no.2
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    • pp.184-194
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    • 2010
  • Purpose : The aim of this study was to evaluate the incidence of febrile urinary tract infection (UTI) according to clinical characteristics in patients with congenital hydronephrosis (CH) and hydronephrotic patients first diagnosed with hydronephrosis during treatment of febrile UTII. Methods : In this study, 200 patients with congenital hydronephrosis were enrolled in group 1 and 252 patients first diagnosed with hydronephrosis during treatment of febrile UTI were enrolled in group 2. We counted the episodes of UTI in the two groups according to clinical characteristics, the presence of VUR, type of feeding, and clinical outcomes since 2000. And we compared those results between the two groups. and compared two groups as well. Results : The incidence of recurrent UTI was 10%, 0.028 per person-year in group 1 and 16.7%, 0.051 per person-year in group 2, respectively (P <0.05). Group 2 had more VUR (3% vs. 27%, P <0.05) and higher incidence of UTI than group 1. The incidence of UTI in patients with CH of Society of Fetal Urology (SFU) grade 4 or grade 4-5 VUR was 80% and 44.4%, respectively. No significant differences were found in incidence of UTI between BMF (breast milk feeding) and artificial milk feeding group in both groups (P 1=0.274, P 2=0.4). The time of resolution of CH had no correlation with either number of UTI episodes or the presence of VUR. Conclusion : The overall incidence of UTI is low in patients with CH as well as patients patients first diagnosed with hydronephrosis during treatment of febrile UTI except patients with SFU grade 4 or grade 4-5 VUR. BMF has no protective effect against UTI.

Peritonitis in Children Undergoing Peritoneal Dialysis: 10 Years' Experience in a Single Center (소아 복막 투석 환자에서 발생한 복막염: 단일기관에서 10년간의 경험)

  • Lee, Se-Eun;Han, Kyoung-Hee;Jung, Yun-Hye;Lee, Hyun-Kyung;Kang, Hee-Gyung;Cheong, Hae-Il;Ha, Il-Soo
    • Childhood Kidney Diseases
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    • v.14 no.2
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    • pp.174-183
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    • 2010
  • Purpose : The organisms causing peritonitis and their antibiotic sensitivities vary in different regions and centers, and these data are necessary to establish regional treatment guidelines. The aim of this study was to investigate the changes in incidence and characteristics of the organisms that cause peritonitis in children undergoing peritoneal dialysis (PD) during recent 10 years. Methods : We retrospectively collected and analyzed the data from medical records of 110 children on PD during the period from 2000 to 2010. Results : One hundred and forty episodes of peritonitis have occurred in 57 patients. The overall incidence of peritonitis was 0.43 episodes/patient year, and similar incidence have been maintained since 2003. Sixty percent of the patients experienced peritonitis within 1 year of PD, and all patients commencing PD in infancy experienced peritonitis. Gram positive (G (+)), gram negative (G (-)) organisms and fungi were cultured in 58%, 38%, and 4.1% respectively and cultures were negative in 13.6%. Staphylococcus was the most common G (+) organism, and Pseudomonas and Acinetobacter were 2 most frequent G (-) organisms isolated. Fifty-six percent of the G (+) organisms were sensitive to first generation cephalosporin and 91% of G (-) pathogens were sensitive to ceftazidime. Methicillin-resistance rate was not higher in children less than 2 years of age than in those more than 2 years. Conclusion : An additional breakthrough has to be made to further reduce the incidence of peritonitis. Treatment guideline customized for peritonitis in Korean children on PD need to be established through a nationwide co-work.

Influence of VEGF Genetic Polymorphism on Peritoneal Solute Transport in Pediatric Dialysis Patients (소아 복막투석환자에서 혈관내피성장인자 유전자 다형성이 복막의 용질이동성에 미치는 영향)

  • Choi, Hyun-Jin;Paik, Kyung-Hoon;Cho, Hee-Yeon;Kang, Hee-Kyung;Cheong, Hae-Il;Choi, Yong;Ha, Il-Soo
    • Childhood Kidney Diseases
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    • v.14 no.2
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    • pp.166-173
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    • 2010
  • Purpose : Genetic and clinical factors can influence the permeability of the peritoneal membrane. The peritoneal equilibration test (PET) is helpful in measuring peritoneal permeability in peritoneal dialysis (PD). We investigated the influence of genetic polymorphism of vascular endothelial growth factor (VEGF) on the PET parameters. Methods : Pediatric patients who underwent PET within 12 months of initiating PD at Seoul National University Children's Hospital and Samsung Medical Center were selected. The patients with positive history of peritonitis before PET were excluded. The VEGF -2578C/A, -14978T/C, -1154G/A, -634G/C, and +936C/T single-nucleotide polymorphisms were genotyped. Results : The mean 4-hour dialysate-to-plasma ratio for creatinine (D/P creatinine) and the mean 4-hour dialysate glucose to baseline dialysate glucose ratio (D/$D_0$ glucose) were $0.56{\pm}0.13$ and $0.43{\pm}0.11$, respectively. The patients with haplotype CTGGC showed higher 4-hour D/P creatinine ($0.67{\pm}0.12$ vs $0.50{\pm}0.09$, P=0.007) and lower 4-hour D/$D_0$ glucose ($0.35{\pm}0.12$ vs $0.47{\pm}0.08$, P=0.037) than those without haplotype CTGGC. Conclusion : The VEGF genetic polymorphism may influence the peritoneal solute transport.

Clinicopathologic Changes of IgA Nephropathy in Children During Long-term (average 10.8 yrs) Follow-up (소아 IgA 신병증의 장기 추적(평균 10.8년)에 따른 임상 경과 및 병리학적 변화)

  • Moon, Chang-Min;Kim, Pyung-Kil;Lim, Beom-Jin;Song, Ji-Sun;Jeong, Hyeon-Joo
    • Childhood Kidney Diseases
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    • v.14 no.2
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    • pp.154-165
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    • 2010
  • Purpose : We know little about the natural course of IgA nephropathy (IgAN) in association with histologic changes especially in children. We investigated clinicopathologic features with long-term follow-up biopsy to clarify the outcomes and prognostic indicators for childhood IgAN. Methods : From our patients' medical records, we retrieved 20 patients with IgAN, to whom renal biopsies had been performed for the initial diagnosis and follow-up to find out any histologic changes. Initial and follow-up biopsies were classified by Haas classification. The changes of these parameters were compared with the evolution of clinical features. Results : Patients were treated with angiotensin-converting enzyme inhibitors in combination with angiotensin receptor blockers (in subclass II or above) and short-term cyclosporine A(in patients showing nephrotic syndrome). Histologic improvement in 7 cases and deterioration in 3 cases were observed. At the time of last biopsy, 10 cases (50%) showed clinical remission and the others showed improved clinical features. These clinical outcomes did not correlate with initial Haas classifications. Hypertension at onset observed in 5 cases (25%) revealed significant correlation with clinical outcome (P =0.01) and last Haas classification (P =0.007). None of the cases showed progression to CRF or ESRD. Conclusion : During a mean follow-up of $10.8{\pm}3.4$ years, childhood IgAN showed good clinicopathologic outcome. Hypertension at onset was only a strong predictor of clinicopathologic outcomes, but initial Haas classification cannot predict outcomes in children. Histologic change of IgAN in long term follow-up period cannot be completely predicted by clinical data and vice versa. Therefore, a renal biopsy should be considered as a part of follow-up plan.

Comparison of Clinical Outcome According to the Duration of Corticosteroid Therapy in Childhood Henoch-$Sch{\ddot{o}}nlein$ Purpura: a Bicentric Study (소아 Henoch-$Sch{\ddot{o}}nlein$ purpura에서 스테로이드 치료 기간에 따른 임상적 결과의 비교)

  • Lee, Su-Jin;Shin, Jae-Il;Lee, Chong-Guk;Kim, Kee-Hyuck
    • Childhood Kidney Diseases
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    • v.12 no.2
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    • pp.170-177
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    • 2008
  • Purpose : The aim of this study was to evaluate whether the incidence of relapse or nephritis might be influenced by the duration of corticosteroid therapy in children with Henoch-Schonlein purpura(HSP). Methods : We retrospectively analyzed 186 children with a diagnosis of HSP in two major hospitals in Ilsan, Korea from the years 2000 to 2003. To evaluate whether renal involvement or relapse might be influenced by the duration of corticosteroid therapy in children with HSP, one pediatric nephrologist from hospital A, maintained corticosteroid therapy for at least 2 weeks(Group A, n=94). The other from hospital B used only during the symptomatic period(Group B, n=92). Results : There were no significant differences in age, sex, body weight, white blood cell count, hemoglobin, hematocrit, platelet count, serum protein and albumin levels between the two groups. The incidence of abdominal pain or arthralgia also did not differ between two groups. However, the duration of steroid therapy was significantly longer in Group A than in Group B and the cumulative dose of prednisolone was also higher in Group A than in Group B. The development of nephritis was more frequent in Group A. Conclusion : The longer duration of steroid use was not associated with the decreased rate of nephritis. Therefore, corticosteroids should be used carefully in a selected group of HSP children, and be tapered rapidly after control of the acute symptoms.

Peritoneal Dialysis Associated Peritonitis and Empirical Antibiotics Therapy in Korean Children with Chronic Renal Failure (소아 복막 투석 환자에서 발생한 복막염의 경험적 항생제 치료에 관한 연구)

  • Lee, Sang-Goo;Cho, Joong-Bum;Sohn, Young-Bae;Park, Sung-Won;Kim, Su-Jin;Jin, Dong-Kyu;Paik, Kyung-Hoon
    • Childhood Kidney Diseases
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    • v.12 no.2
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    • pp.213-220
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    • 2008
  • Purpose : This study aims to verify the effectiveness of initial empirical antibiotic choice recommended by the International Society for Peritoneal Dialysis(ISPD) guide among Korean children. Methods : We have collected data on peritonitis from January 2001 to December 2007 in Samsung Medical Center. Results : Of the 42 patients, 48 episodes of peritonitis had occurred in 21 patients. The rate of peritonitis was one episode over 35.3 patient-months. Mean dialysis duration before peritonitis was 18.06$\pm$15.81 months. Gram-positive organisms accounted for 58.3% of all episodes. Of the gram-positive organisms, the most common pathogen was Staphylococcus aureus(29.2%), the next common pathogens were Coagulase negative staphylococcus(14.6%) and Streptococcus species(6.3%). 35.7% of gram-positive pathogens were resistant to 1st cephalosporin. However, in patients younger than 4 years old, 50% of gram-positive pathogens were resistant to 1st generation cephalosporin. 10 episodes of peritonitis were methicillin-resistant and were treated by vancomycin. Of the gram-negative organisms, E. coli was the most common (8.3%). 64.8% of all pathogens were sensitive to cephalothin or ceftazidime. Conclusion : The empirical therapy with 1st generation cephalosporin and ceftazidime can be also effective to peritoneal dialysis associated peritonitis in Korean children. However, in patients younger than 4 years old, glycopeptide should be considered as the first empirical therapy in Korean children.

Changes of Clinical Findings of Acute Poststreptococcal Glomerulonephritis (소아에서 연쇄상 구균 감염 후 급성 사구체 신염의 임상양상의 변화)

  • Choi, Byung-Ho;Chu, Mi-Ae;Hong, Eun-Hui;Hwang, Hyun-Hee;Cho, Min-Hyun;Ko, Cheol-Woo
    • Childhood Kidney Diseases
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    • v.12 no.2
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    • pp.157-163
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    • 2008
  • Purpose : Several studies have reported the recent increase in the incidence of acute poststreptococcal glomerulonephritis(APSGN). The objective of this study is to see changes of clinical findings/manifwstation in children with APSGN. Methods : Medical records of 63 children who were diagnosed with APSGN in the deparment of Pediatrics, Kyungpook National University Hospital, between January 1992 and December 2006 were reviewed retrospectively. We analyzed various clinical characteristics such as age, sex, degrees of proteinuria, degrees of hematuria, and presence or absence of histories of systemic antibiotic use in children with APSGN, and compared the children with APSGN who were diagnosed between 1992 and 2000 to those who were diagnosed between 2001 and 2006. Results : Age of the patients ranged from 2-14 years(median 7.11 years) at the time of disease onset. Study patients consisted of 41 boys and 22 girls. APSGN followed infection of the throat in 87% of cases. Patient developed an acute nephritic syndrome 12 days after an antecedent streptococcal pharyngitis. Forty patients presented with gross hematuria. Fortyone patients had hypertension at the time of diagnosis. Hypertension disappeared within 7.8$\pm$8.2 days, gross hematuria within 11.3$\pm$17.2 days and microscopic hematuria within 3.5$\pm$3.9 months from the disease onset. Patients in 2001-2006 had significantly higher increase of antistreptolysin O(ASO) titer. However, no significant differences in clinical characteristics were observed. Age, sex, severity of proteinuria, gross or microscopic hematuria, antibiotic therapy did not affect the clinical manifestations of glomerulonephritis. In other words, hypertension, duration of hematuria, recovery of serum C3 level are not different between the two time periods. Conclusion : Our data indicates that patients in 2001-2006 had significantly higher level of ASO titer. However, they did not show significant clinical differences. To evaluate the causes of the resurgence of APSGN, a national epidemic is needed.