• Childhood Kidney Diseases
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• v.11 no.1
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• pp.24-31
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• 2007

Purpose : Nitric oxide(NO) is a very potent vasodilator synthesized from L-arginine by endothelial cells. We investigated whether urinary NO excretion was altered in various renal diseases in children and whether urinary NO excretion could be used in predicting pathologic causes and fibrosis in renal diseases in children. Methods : We recruited 48 patients(32 minimal change nephrotic syndrome[MCNS] and 16 vesicoureteral reflux[VUR] patients from the pediatric renal clinic in Korea University Guro Hospital. We measured the concentration of nitrite$(NO_2)$ and nitrate$(NO_3)$ by Griess reaction and that of creatinine(Cr) by Jaffe method in randomized spot urines. We then analyzed the urinary$(NO_2+NO_3)/Cr$ ratios and compared the values between each patient group. Urinary $(NO_2+NO_3)/Cr$ ratios were also evaluated according to the recurrence and the degree of proteinuria at sampling in the MCNS group and compared according to the presence of renal scarring and the grade of reflux in the VUR group. Results : The ratios of urinary$(NO_2+NO_3)/Cr$ were significantly increased in the VUR and MCNS groups, as compared to the control group. In the MCNS group, a higher level of urine $(NO_2+NO_3)/Cr$ was observed In frequent relapse patients(relapse over four times within one year after first diagnosis) and the patients with severe proteinuria at sampling, respectively. The VUR group with renal scars also showed a higher level of urinary$(NO_2+NO_3)/Cr$ compared to that without scars. Conclusions : In summary, VUR may play a role in the pathogenesis of VUR and MCNS. NO also seems to affect proteinuria and renal scar formation. (J Korean Soc Pediatr Nephrol 2007;11:24-31)

• Childhood Kidney Diseases
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• v.18 no.1
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• pp.36-41
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• 2014

Purpose: Urinary tract infections (UTIs) are the most common source of bacterial infections in infants and young children. Accurate diagnosis and treatment is important because of their association with renal scarring, which can lead to complications. Urine endothelin-1 (ET-1) is the major renal isoform produced and released by renal mesangial cells in response to glomerular injury. This study aimed to investigate whether urinary levels of ET-1 can be used as a biomarker for UTI diagnosis. Method: We conducted a prospective study using medical records of 70 patients below the age of 18 years, who visited Chung-Ang University Hospital from July 2012 to July 2013. We classified the patients into the UTI and control groups based on urine culture studies. The UTI group was further divided into upper and lower UTI groups using 99m-Technetium dimercaptosuccinic acid scintigraphy. Urine ET-1 was measured using enzyme linked immunosorbent assay with 0.3 mL urine. Results: The UTI and control groups were comprised of 45 and 25 patients, respectively. Mean urine ET-1 levels were significantly higher in the UTI group than in the control group ($1.41{\pm}0.35$ pg/mL vs. $0.33{\pm}0.07$ pg/mL, P =0.04). There was no significance difference in the quantitative value between the upper and lower UTI groups (P =0.552). There was no correlation between urine ET-1 and serum C-reactive protein (Pearson correlation [R]=0.24), urine ET-1 and serum white blood cell count (R=0.19). Conclusion: Our study suggests that urine ET-1 can be used for early diagnosis of UTI in children.

• Childhood Kidney Diseases
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• v.12 no.1
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• pp.62-69
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• 2008

Purpose: The most concerning issue in children with urinary tract infection(UTI) is the probability of underlying genitourinary anomalies and vesicoureteral reflux (VUR), which is frequently associated with renal scarring and eventually end-stage renal disease. Therefore, voiding cystourethrography(VCUG) is usually recommended at the earliest convenient time for children with UTI. However, VCUG is an invasive procedure that requires catheterization and exposure to X-ray. In this study, we aimed to determine the predictability of clinical, laboratory and imaging parameters for VUR in children with UTI. Methods: Data of children with bacteriologically proven UTI who underwent VCUG were evaluated retrospectively for clinical(age, gender, fever), laboratory(leukocytosis, ESR, CRP, pyuria, blood urea nitrogen, serum creatinine) and imaging(renal ultrasound and DMSA renal scan) findings. First, children with UTI were divided into two groups according to the presence of VUR as non-VUR group and with VUR group, and clinical, laboratory variables were compared between these groups. Second, patients who had VUR were reclassified as low-grade VUR(grade I-II) group and high-grade(grade III-V) VUR group according to grading of VUR, and clinical, laboratory and imaging variables were compared between these groups. Results: Among 410 children with UTI, 137 had VUR and 78 high-grade VUR. Fever, leukocytosis, ESR, CRP, pyuria were associated with VUR. In addition, abnormal findings of ultrasonography and DMSA renal scan were closely related to VUR. However, these clinical and laboratory variable in patients with high grade VUR were not different significantly, compared to those with low-grade VUR group. Conclusion: Fever, leukocytosis, ESR, CRP seems to be potentially useful predictors of VUR in pediatric patients with UTI. In addition, renal ultrasonography and DMSA renal scan findings supported the presence of VUR. Further study of these findings could limit unnecessary VCUG in patients with UTI.

• 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.

• Tuberculosis and Respiratory Diseases
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• v.50 no.1
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• pp.76-83
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• 2001

Background : Coal workers' pneumoconiosis is a fibrotic lung disease resulting from chronic inhalation of coal dust. The precise mechanism of lung fibrosis in coal workers' pneumoconiosis is uncertain. However, a relationship between the stimulation of fibroblast proliferation and collagen production by mediators released from in flammatory and resident lung cells is thought to be a major factor. The transforming growth factor-$\beta$(TGF-$\beta$), a multifunctional cytokine and growth factor, plays a key role in the scarring and fibrotic processes due to its ability to induce extracellular matrix proteins and modulate the growth and immune function of many cell types. To determine the involvement of TGF-$\beta$ in the development of lung fibrosis in coal workers' pneumoconiosis, the TGF-${\beta}_1$ level in plasma was measured in patients with coal workers' pneumoconiosis. Methods : Plasma was collected from 40 patients with coal workers' pneumoconiosis (20 with simple coal workers' pneumoconiosis and 20 with complicated coal workers' pneumoconiosis) and from 10 normal controls. The ELISA method was used to measure the plasma TGF-${\beta}_1$ concentration. Results : Compared to the control group ($0.63{\pm}01.8$ ng/mL), there was no significant difference in the plasma TGF-${\beta}_1$ level in patients with simple coal workers' pneumoconiosis ($0.64{\pm}0.17$ ng/mL) (p>0.05). However, in patients with complicated coal workers' pneumoconiosis the plasma TGF-${\beta}_1$ level ($0.79{\pm}0.18$ ng/mL) was significantly higher than in patients with simple coal workers' pneumoconiosis and the control group (p<0.05). Conclusion : The data suggests that TGF-${\beta}_1$ has some influence in the development of lung fibrosis in coal workers' pneumoconiosis.

• Childhood Kidney Diseases
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• v.9 no.1
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• pp.46-55
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• 2005

Purpose : Recurrent urinary tract Infection(UTI) in primary vesicoureteral reflux(VUR) may lead to serious renal scarring, a major cause of childhood hypertension and end-stage renal disease. To prevent recurrent UTI, low-dose long--term antibiotic prophylaxis has been recommended. However, recurrent UTI still develops during antibiotic prophylaxis, the efficacy of which is now being disputed. The emergence of resistant bacteria has also raised concerns. To evaluate the effect of antibiotic prophylaxis, we investigated recurrent UTI during prophylactic antibiotic use in children with primary VUR Materials : The incidence and risk factors of recurrent UTI were retrospectively evaluated in ninety-one children with primary VUR on trimethoprim- sulfamethoxazole(TMP/SMX) prophylafis during the year following their index febri]e UTI. Results : Recurrent UTI occurred in 31.9%(29/91) children and comprised 0.32 episodes/patient year. Febrile UTI was 0.26 episode/patient year and afebrile UTI was 0.07 episodes/patient year. The recurrent rate of UTI in male patients with phimosis was 37.2%(19/51), which was significantly higher than in males without phimosis 0%(0/5)(P=0.025). In the logistic regression analysis for recurrent UTI, renal scar was the significant risk factor for recurrent UTI [RR 3.8(95% CI 1.0-14.1) P=0.04]. For other well-known risk factors such as sex, age, degree of VUR, APN, and voiding dysfunction, the differences were not significant. Conclusion : TMP/SMX prophylaxis did not prevent recurrent UTI in children with primary VUR. Phimosis and renal scars were the risk factors for recurrent UTI but the grade of primary VUR was not. In VUR without phlmosis and renal scar, a randomized controlled study without antibiotic prophylaxis is required. (J Korean Soc Pediatr Nephrol 2005;9:46-55)

• Childhood Kidney Diseases
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• v.10 no.1
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• pp.18-26
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• 2006

Purpose : Empirical antimicrobial treatment is indicated before bacteriological results are available for young children with febrile UTI to minimize renal scarring. To ensure appropriate therapy, knowledge of the prevalence of causative organisms and their susceptibility patterns to antimicrobials is mandatory. We performed a retrospective analysis investigating the local prevalence and resistance patterns of uropathogens, primarily E. coli, isolated from community-acquired UTIs. Methods : A total of 103 positive urine cultures from children with febrile UTI collected at Bundang CHA General Hospital from February 2004 to February 2005 were analyzed. Inclusion criteria were fever higher than $37.5^{\circ}C$, significant bacteriuria with single strain growth of at least 10s colony forming units/mL urine, and leukocyturia >5/HPF. Results : E. coli(89.3%) was the leading uropathogen followed by Enterococcus spp.(3.9%) Klebsiella spp.(2.9%), Citrobctcter spp.(1.9%) and Enterobacter spp.(1.9%). E. coli strains revealed a low proportion of antimicrobial susceptibility to ampicillin(AMP; 27.2%) ampicillinsulbactam(AMS; 34.8%) and trimethoprim-sulfamethoxazole(SXT; 65.2%). Susceptibility patterns to cephalosporins were as follows; cefazolin(1st generation; 91.3%), cefoxitin(2nd; 100%), ceftriaxone(3rd; 97.8%) and cefepime(4th; 97.8%). Three E. coli isolates produced ex tended - spectrum beta-lactamase(ESBL). Conclusion : Empirical treatment with AMP, AMS and SXT, which are commonly used in pediatric clinics, is not recommended for childhood UTI due to high incidence of resistance. The high level of susceptibility to cephalosporins makes these drugs reasonable alternatives. However the emergence of ESBL-producers, even though they are quite few, may have an impact on cephalosporin treatment in the future. (J Korean Soc Pediatr Nephrol 2006;10:18-26)

• Childhood Kidney Diseases
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• v.17 no.2
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• pp.65-72
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• 2013

Purpose: Urinary tract infection (UTI) caused by gram-positive uropathogens is usually hospital-acquired and associated with predisposing conditions. However, the incidence of gram-positive bacteria in community-acquired UTIs has recently increased worldwide. We aimed to investigate the clinical significance of UTI and associated genitourinary malformations in young children with febrile UTIs caused by gram-positive bacteria. Methods: We retrospectively reviewed the medical records of 566 patients (age, <1 year) who visited the Korea University Medical Center for febrile UTIs between January 2008 and May 2013. We classified the patients into the following two groups: gram-positive (P group) and gram-negative (N group), according to the results of urine culture. The fever duration; white blood cell (WBC) counts and C-reactive protein (CRP) levels in peripheral blood; and the presence of hydronephrosis, cortical defects, vesicoureteral reflux (VUR), and renal scarring were compared between the two groups. Results: The number of patients with gram-positive bacteria was 23 (4.1%) and with gram-negative bacteria was 543 (95.9%). The most common pathogen was Escherichia coli, and Enterococcus faecalis showed the highest incidence among gram-positive uropathogens. Patients with gram-positive bacteria showed longer fever duration compared to that in patients with gram-negative bacteria (P vs. N, $3.4{\pm}1.2$ vs. $2.9{\pm}1.6$ days, P <0.05). The incidence of VUR was increased in the gram-positive group compared to that in the gram-negative group (P vs. N, 55.6 vs. 17.8%, P<0.05). However, there were no significant differences in other laboratory and radiologic findings. Conclusion: The findings of our study show that community-acquired UTIs in patients younger than 1 year of age, caused by gram-positive uropathogens, can be associated with prolonged fever duration and the presence of VUR.

• Childhood Kidney Diseases
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• v.17 no.2
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• pp.110-116
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• 2013

Purpose: The $^{99m}Tc$-Dimercaptosuccinic acid (DMSA) renal scan is used primarily for the diagnosis of renal scarring and acute pyelonephritis in children with urinary tract infections (UTI). This study aimed to evaluate clinical differences based on the positive or negative results of DMSA scans and kidney ultrasonography (US) in pediatric UTI. Method: We retrospectively reviewed 142 pediatric patients with UTI who were admitted to Myongji Hospital from January 2004 to December 2012. We performed a comparative analysis of clinical parameters such as age, sex, white blood cell (WBC) count, neutrophil count, blood urea nitrogen (BUN) level, creatinine (Cr) level, C-reactive protein (CRP) level, and durations of hospitalization and fever, grouped by the results of the DMSA scans and kidney US. Results: The mean age of the patients was $33.8{\pm}48.3$ months, and 78 (55%) were male. Fifty-two patients had abnormal DMSA findings, and 71 patients had abormal kidney US findings (test positive groups). In the DMSA scan positive group, there were significant differences in age, WBC counts, neutrophil counts, CRP level, BUN level, Cr level, hospitalization duration, number of abnormal findings on kidney US, and incidence of vesicoureteral reflux (VUR) compared with the scan negative group. The kidney US positive group had significant differences in age, neutrophil count, CRP level, BUN level, Cr level, hospitalization duration, number of abnormal findings on the DMSA scans, and more frequent VUR compared with the US negative group. Conclusion: Our data suggest that there were no major differences in clinical parameters based on the results of the DMSA scans compared with kidney US in pediatric UTI. However, as kidney US and DMSA scan were performed to predict VUR, the sensitivity and negative predictive value was increased.

• Journal of The Korean Ophthalmological Society
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• v.59 no.11
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• pp.1039-1048
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• 2018

Purpose: To evaluate the effects of anti-vascular endothelial growth factor (VEGF) treatment on the healthcare-related finances of patients with age-related macular degeneration. Methods: Changes in health care financing due to newly introduced benefit standards were predicted over the coming 5-year period (2018-2022). We also analyzed the financial impact of scenarios in which agents similar to anti-VEGF, such as the over-licensed drug bevacizumab, were introduced. For this purpose, the future number of patients receiving anti-VEGF treatments was estimated for various scenarios based on National Health Insurance Corporation claims data followed by an estimate of the financial burden. Results: In the case of age-related macular degeneration, the current standard of care (14 times in a lifetime) was maintained in scenario 1. In 2018, the insurance budget for the coming 5-year period was estimated at approximately 440.3 billion won. The insurance cost for that period was estimated at approximately 560.1 billion won under the revised standard of December 2017 (scenario 2). For scenarios wherein, after 2020, similar treatments (scenario 3) and bevacizumab (scenario 4) were introduced, the estimated health insurance costs were 521 billion won and 419.7 billion won, respectively. Conclusions: Health insurance costs are projected to increase substantially due to the elimination of the 14 time pay standard; however, the actual budget will only moderately increase, due to new limitations of visual acuity ${\leq}0.1$ or in case of scarring/atrophic lesions. Clinically similar agents and bevacizumab could be considered as alternatives to anti-VEGF treatment for age-related macular degeneration.