• The Journal of Internal Korean Medicine
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• v.35 no.1
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• pp.92-105
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• 2014

Objectives : Cisplatin is a widely used cancer therapy drug. However, nephrotoxicity resulting in increased oxidative stress is a major side effect of cisplatin chemotherapy, thereby limiting its chemotherapeutic use. Lycium chinense Miller (LCM) has been used as a traditional herbal medicine in various febrile and inflammatory diseases such as night sweat, cough, nosebleed, bronchitis, pulmonary tuberculosis, etc. In this study we investigated the protective and antioxidative potential of LCM against cisplatin-induced nephrotoxicity in rats. Methods : Twenty-four 8-week-old male Wistar rats were divided into four groups: normal untreated; cisplatin treatment only; LCM 10 mg/kg plus cisplatin treatment; and LCM 30 mg/kg plus cisplatin treatment. Twenty-four hours after the last cisplatin injection, all the rats were sacrificed, and serological changes were evaluated. The levels of NF-${\kappa}B$ activity and NOX-4, $p47^{phox}$, $p22^{phox}$, COX-2, iNOS, SOD, catalase expressions were analyzed in Western blot analysis. Results : Cisplatin injection caused an increase in the BUN level, which is a reliable indicator of renal toxicity. The levels of BUN, renal ROS, and renal TBARS were significantly reduced in the LCM groups compared with the cisplatin-only groups. The levels of $p47^{phox}$ and $p22^{phox}$, which are NADPH oxidase subunits, were increased in the cisplatin-only groups, whereas they were decreased in the LCM groups. The levels of renal NF-${\kappa}B$ activity and COX-2, iNOS expressions were increased significantly in the cisplatin-only groups compared with the normal groups, whereas they were decreased in the LCM groups. Compared with the cisplatin-only groups, renal GSH and GSH/GSSG increased in the LCM groups. Also, the administration of LCM increased levels of SOD and catalase as compared with the cisplatin-only groups. Conclusions : These results suggest that LCM protects cisplatin-induced nephrotoxicity via a mechanism that may involves the inhibition of oxidative stress by the activation of antioxidants.

• Childhood Kidney Diseases
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• v.3 no.1
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• pp.80-87
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• 1999

Purposes : Renal involvement is a potentially serious complication of systemic lupus erythematosus (SLE). There have been only few studies of lupus nephritis in pediatric age. In this study, the clinical manifestations, pathologic findings, response to treatment, and clinical course of lupus nephritis in children were analyzed. And the results will provide basic data for future nation-wide prospective multi-center study. Methods . The medical records of 46 children clinically and pathologically diagnosed to have lupus nephritis at Seoul National University Children's Hospital during 1986 to 1997 were analyzed retrospectively. Results : 1) The median age of diagnosis of lupus nephritis was 12.8 years ($2\;years\~\;15year$ 8months), and the sex ratio was 1:2.5. 2) FANA($85.7\%$), anti-ds-DNA antibody ($78.0\%$), and malar rash ($60.8\%$) were the most common findings among the classification criteria by ARA Decreased C3 was detected in $88.9\%$ of patients. 3) Hematuria ($87.0\%$) was the most common renal symptom, and WHO class IV lupus nephritis was identified in 41 cases by renal biopsy. 4) In most of patients, the disease activity was controlled relatively well with a single or combined therapy of prednisolone, azathioprine, or cyclophosphamide. The response revealed no difference according to the mode of treatment. 5) Infection, especially of Varicella-Zoster virus and candida, was the most common complication during the disease course. Conclusion : The renal involvement was noted in $87.0\%$ of childhood SLE, and $89.1\%$ of renal lesions was WHO class IV lupus nephritis known to associated with poor long-term prognosis. So, aggressive treatment using immunosuppressants in the early disease course may be helpful to increase long-term prognosis of lupus nephritis. A prospective multi-center study is necessary to analyze the therapeutic efficacy of various treatment modalities.

• Childhood Kidney Diseases
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• v.2 no.2
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• pp.125-132
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• 1998

Purpose : To study whether a low protein diet increase the efficacy of antihypertensive therapy on the progression of renal failure, we conducted an experimental study using 5/6 nephrectomized rats(n=63). Methods : At 7 days after surgery, rats were randomly assigned to three groups according to receiving antihypertensive drug: no antihypertensive drug (U), enalapril (E), and nicardipine (N), respectively and fed a low protein diet (6$\%$ protein). Proteinuria, mesangial matrix expansion score and glomerular volume were assessed at 4, 12 and 16 weeks after renal ablation. Results : Group U rats on a low protein diet developed progressive hypertension ($140{\pm}8,\;162{\pm}5,\;171{\pm}5\;and\;184{\pm}11\;mmHg$ at 4, 8, 12 and 16 weeks) which were controlled by E and N. Group U rats on a low protein diet developed proteinuria ($74{\pm}15\;mg/day$ at 16 weeks) which were decreased by E ($42{\pm}12 mg/day$) or N ($48{\pm}8 mg/day$) (p<0.05). Mesangial matrix expansion score and glomerular volume were not different between groups U, E and N on a low protein diet regardless of the antihypertensive drugs administered. Conclusion : A low protein diet did not affect blood pressure. Enalapril and nicardipine-treated rats on a low protein diet did not have different mesangial matrix expansion and glomerular volumes from rats on a low protein diet at 12 weeks and 16 weeks, in spite of the better controlling of systemic hypertension and lessening of proteinuria. Thus, combined treatment with a low protein diet and antihypertensive drugs didn't appear to show any addition,11 effects to attenuate glomerular injury.

• Childhood Kidney Diseases
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• v.11 no.1
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• pp.74-82
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• 2007

Purpose : To analyze the clinical characteristics, spontaneous resolution rate and predictive factors of resolution in children with primary vesicoureteral reflux(VUR). Methods : Between October 1991 and July 2003, 149 children diagnosed with primary VUR at Chonbuk National University Hospital were reviewed retrospectively. All of the patients were maintained on low-dose antibiotic prophylaxis and underwent radionuclide cystograms at 1 year intervals over 3 years after the initial diagnosis of VUR by voiding cystourethrogram was made. Results : The median time to resolution of VUR was 24 months and the total 3 year-cumulative resolution rate of VUR was 61.7%. The following variables were associated with resolution of VUR according to univariate analysis-; age<1 year, male gender, mild grade of reflux, unilateral reflux, congenital hydronephrosis as clinical presentation at time of diagnosis of VUR, absence of focal defects in the renal scan at diagnosis, absence of recurrent UTI, renal scars and small kidney during follow-up. After adjustment by Cox regression model, five variables remained as independent predictors of VUR resolution; age<1 yew, relative risk 1.77(P<0.05), VUR grade I+II 2.98(P<0.05), absence of renal scars 2.23(P<0.05), and absence of small kidney 5.20(P<0.01) during follow-up. Conclusion : In this study, spontaneous resolution rate of VUR, even high grade reflux, is high in infants during medical management, and it was related to age, reflux grade at diagnosis, absence of renal scars and small kidney during follow-up. Therefore early surgical intervention should be avoided and reserved for the selected groups.

• Childhood Kidney Diseases
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• v.11 no.2
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• pp.239-246
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• 2007

Purpose : The progressive deterioration of renal function in children can impose a serious and lifelong impact on their lives. The ultimate goal in the management of children with chronic kidney disease(CKD) is to prolong survival, to prevent complications, and to promote growth and neurodevelopment. The aim of this study is to investigate the risk factors for the decline of renal function in pediatric CKD patients. Methods : Data from patients who met the criteria for the Kidney Disease Outcomes Quality Initiative(K/DOQI) CKD stage 2 to 4 between August 1999 and March 2007 were retrospectively analyzed. The estimated glomerular filtration rate(eGFR) was calculated by the Schwartz formula, using serum creatinine levels and height. We calculated the annual eGFR change from the difference between the baseline eGFR and the last eGFR divided by the duration(years) of the follow-up period. We analyzed the association between the annual eGFR change and factors such as age, gender, K/DOQI stage, underlying renal disease, serum calcium, and inorganic phosphorous during the follow-up period. Results : Sixty one children(44 boys & 17 girls) were enrolled. The age at entry was $7.1{\pm}4.7$ years. The annual eGFR change was $-1.2{\pm}11.9 mL/min/1.73m^2/year$. Our study showed that older age(P=0.005). hypocalcemia(P=0.012), and hypenhosphatemia(P=0.002) were significantly related to more rapid decline in renal function. Conclusion : In pediatric CKD, older age, hypocalcemia and hyperphosphatemia are related to more rapid deterioration of renal function.

• Childhood Kidney Diseases
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• v.7 no.1
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• pp.60-66
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• 2003

Purpose : Neonatal hydronephrosis has been detected with increasing frequency with the widespread use of prenatal ultrasonography, but the consensus about its postnatal management has not yet been reached, especially about surgical intervention. We attempted to determine the guideline of follow-up study and surgical intervention of hydronephrosis by analyzing clinical outcomes of neonates with hydronephrosis. Materials and Methods : Between 1994 and 2000, 128 hydronephrotic kidneys were postnatally confirmed. Cases associated with other urologic anomalies were excluded and 90 unilateral hydronephrotic kidneys with a minimum follow-up of 12 months were enrolled in this study. We classified the patients into 6 groups according to the anterior posterior pelvic diameter(APPD) at initial ultrasonography(USG) within 1 month after birth. Renal USG and $Tc^{99m}-mercaptoacetyl$ triglycerine(MAG3) scan were done according to a set protocol, and pyeloplasty was performed when indicated according to our protocol. Results : Most cases whose APPD were below 10 mm improved or resolved. Only few cases with APPD above 20 mm showed spontaneous improvement and most(88%) had undergone operation. Those with initial APPD within 10-19 mm showed variable outcomes. When the risk factors for irreversible renal functional deterioration were analyzed, the age at pyeloplasty and pre-operative functional deficit were significant. Conclusion : We concluded that in infants with initial APPD below 10 mm, consideration of surgery is not needed, and in those with initial APPD above 20 mm, early operation is recommended. Our set protocol based on initial USG is useful, but the cut-off value of relative renal function(RRF) for operation might be increased to 40% to improve post operative RRF.

• Childhood Kidney Diseases
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• v.9 no.1
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• pp.15-20
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• 2005

Purpose : Nutcracker syndrome must be considered when hematuria or proteinuria occurs in a healthy child. The purpose of this study is to investigate the prevalence of nutcracker syndrome among children with asymptomatic hematuria or proteinuria, and to obtain the ratios of the peak velocity of the left renal vein between the aortomesenteric portion and the hilar portion in children with asymptomatic hematuna or protelnuria in which nutcracker syndrome was excluded and to observe whether the ratios are affected by sex, age or urinalysis findings. Methods : Using Doppler ultrasonography, we measured the flow velocity and obtained the peak velocity ratios of the left renal vein at the aortornesenteric portion and at the hilar Portion of the left kidney in children with asymptomatic hematuria or proteinuria who visited the Division of Pediatric Nephrology, Severance Hospital from May 2001 to March 2004. Results : Of 304 children with asymptomatic hematuna or proteinuria, 107 children(35.2%) were diagnosed with nutcracker syndrome. For 197 children with asymptomatic hematuria or proteinuria excluding nutcracker syndrome, the mean ratio of the peak velocity was 2.54 $\pm$0.73, which was not affected by sex, age or urinalysis findings. Conclusion : Nutcracker syndrome was the major cause of asymptomatic hematuria or proteinurla In children, comprising 35% of all cases. Doppler ultrasonography was helpful in the screening of nutcracker syndrome and prevention of its complications. For children with asymptomatic hematuria or proteinuria excluding nutcracker syndrome, the peak velocity ratio of the left renal vein did not differ from that of normal children and was not affected by sex, age or urinalysis findings. (J Korean Soc Pediatr Nephrol 2005;9:15-20)

• 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.

• IMMUNE NETWORK
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• v.7 no.1
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• pp.31-38
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• 2007

Background: Mizoribine (MZR) is an imidazole nucleoside isolated from Eupenicillium brefeldianum. MZR is currendy in clinical use for patients who have undergone renal transplantation. Therapeutic efficacy of MZR has also been demonstrated in rheumatoid arthritis and lupus nephritis. MZR has been shown to inhibit the proliferation or lymphocytes by interfering with inosine monophosphate dehydrogenase. Since the exact mechanism by which MZR benefits rheumatoid arthritis (RA) is not clear, we investigated the ability of MZR to direct its immunosuppressive influences on other antigen presenting cells, such as macrophages. Methods: Mouse macrophage RAW264.7 cells were stimulated with lipopolysaccharide in the presence of MZR. To elucidate the mechanism of the therapeutic efficacy in chronic inflammatory diseases, we examined the effects of MZR on the production of pro-inflammatory cytokines, nitric oxide (NO) and prostaglandin $E_2\;(PGE_2)$ in macrophages. Results: MZR dose-dependendy decreased the production of nitric oxide and pro- inflammatory cytokines such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukins $1{\beta}$ (IL-${\beta}$ and IL-6 $PGE_2$. Examination of gene expression levels showed that the anti-inflammatory effect correlated with the down-regulation of inducible nitiric oxide synthase expression, cycloxygenase-2 expression and TNF-${\alpha}$ gene expression. Conclusion: In this work, we resulted whether MZR $(1.25{\sim}10{\mu}g/ml)$ inhibited macrophage activation by inhibiting secretion of pro-inflammatory cytokines, NO and $PGE_2$. These findings provide an explanation for the therapeutic efficacy of MZR in chronic inflammation-associated diseases.

• Korean Journal of Health Education and Promotion
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• v.24 no.5
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• pp.39-54
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• 2007

This study attempts to provide fundamental information for a health policy and health services by looking at the trends and types of the mortality rates in Korea and Japan. In this study, data of the death statistics of Korea and Japan over the 21-year period from 1983 to 2003 are analyzed. Mortality data are standardized ${\times}100,000$ to the 2003 Japan population, according to the direct method. In 2001/2003, the ranking of major causes of death in Korea and Japan has been greatly changed. In Korea, mortality rates from malignant neoplasms, diabetes mellitus, renal failure, falls and suicide have increased. In Japan, the mortality rates from pneumonia increase more than those from diabetes mellitus. In 2001/2003, the proportions of the mortality rates from chronic diseases are higher than those from acute diseases. In the Korean health promotion policy "Health Promotion 2020", a more intensive goal management is needed.