• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.5
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• pp.1140-1146
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• 2008

One of the major side effects of cisplatin is nephrotoxicity, leading to acute renal failure. Recent study has suggested a role of hydroxyl radicals and p53 in renal cell injury by cisplatin. This study determined the possible involvement of oxidative stress in p53 activation. In rat mesangial cells, cisplatin treatment induced apoptosis and p53 activation. Pifithrin-$\alpha$, a pharmacological inhibitor of p53, suppressed cisplatin-induced apoptosis. Cisplatin also induced reactive oxidative species (ROS) generation. Of interest, cisplatin-induced apoptosis was prevented by N-acetyl-cysteine (NAC), a general antioxidant. NAC diminished p53 activation during cisplatin treatment. Puerariae Radix and Rehmanniae Radix Preparata with antioxidative activity were reduced the cisplatin-induced ROS generation, caspase-3 activity and p53 activation. In conclusion, ROS may contribute to p53 activation to initiate cisplatin-induced apoptosis in rat mesangial cells. In result, antioxidative effect of Puerariae Radix and Rehmanniae Radix Preparata prevented cisplatin-induced apoptosis through inhibition of p53 activation.

• Childhood Kidney Diseases
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• v.23 no.2
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• pp.59-66
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• 2019

Background: Primary hyperoxaluria (PH), a rare inborn error of glyoxylate meta bolism causing overproduction of oxalate, is classified into three genetic subgroups: type 1-3 (PH1-PH3) caused by AGXT, GRHPR, and HOGA1 gene mutations, respectively. We performed a retrospective case series study of Korean pediatric patients with PH. Methods: In total, 11 unrelated pediatric patients were recruited and their phenotypes and genotypes were analyzed by a retrospective review of their medical records. Results: Mutational analyses revealed biallelic AGXT mutations (PH1) in nine patients and a single heterozygous GRHPR and HOGA1 mutation in one patient each. The c.33dupC was the most common AGXT mutation with an allelic frequency of 44%. The median age of onset was 3 months (range, 2 months-3 years), and eight patients with PH1 presented with end stage renal disease (ESRD). Patients with two truncating mutations showed an earlier age of onset and more frequent retinal involvement than patients with one truncating mutation. Among eight PH1 patients presenting with ESRD, five patients were treated with intensive dialysis followed by liver transplantation (n=5) with/without subsequent kidney transplantation (n=3). Conclusion: Most patients presented with severe infantile forms of PH. Patients with two truncating mutations displayed more severe phenotypes than those of patients with one truncating mutation. Sequential liver and kidney transplantation was adopted for PH1 patients presenting with ESRD. A larger nation-wide multicenter study is needed to confirm the genotype-phenotype correlations and outcomes of organ transplantation.

• Clinics in Shoulder and Elbow
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• v.12 no.1
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• pp.89-93
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• 2009

Purpose: Kimura's disease is an uncommon benign lymphoproliferative inflammatory disorder with an unknown etiology. The recurrence rate after surgical excision is relatively high and renal involvement is its only systemic manifestation. The condition mainly involves the head and neck, and peripheral involvement is extremely rare. Materials and Methods: We encountered the case of a 28-year-old man who had a non-tender mass with mild brownish skin color changes and pruritus around the medial side of the distal arm and elbow. Results: The peripheral blood investigation revealed peripheral eosinophilia and elevated serum IgE levels. Magnetic resonance imaging showed an isointensity signal relative to the muscle on the T1-weighted images and hyperintensity signal relative to the muscle on the T2-weighted images. Conclusion: A marginal resection of the lesion was performed and there was no recurrence at 2 years postoperatively.

• Pediatric Infection and Vaccine
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• v.11 no.1
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• pp.90-100
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• 2004

Objective : Urinary tract infection(UTI) is a frequent serious bacterial infection in young infants. The clinical presentation may be non-specific and variable, depends on factors such as the age and the level of infection. Children with renal involvement may be at risk of permanent renal damage. Experimental studies have shown that renal lesions caused by acute febrile UTI may be prevented or diminished by early diagnosis and treatment. Therefore, it is important to find a method that can permit early diagnosis and identification of patients who are at risk for progressive renal damage. We designed this study to identify related factors in culture positive UTI infants, and also to identify related factors in culture negative UTI infants, who are febrile with pyuria, by using renal imaging and functional studies including renal sonography, DMSA scan and VCUG. Methods : Retrospectively analyzed the medical records of 136 febrile infants with pyuria over 2 years(from January 2001 to February 2003). Urine culture was done in all cases, and regardless of urine culture findings, renal imaging study was done if symptomatic UTI suspected. Results : Total 57 organisms were isolated in 53 patients. E. coli was the most common organism(86%), followed by E. faecalis, M. morganii, Proteus species, P. aeruginosa, S. aureus and E. fergusonii. Most of the isolates had high sensitivity on cephalosporins or amikacin and had low sensitivities on aminopenicillins. Abnormal acute phase DMSA scan or VCUG findings were seen in both urine culture positive and negative group without statistical differences(P>0.05). In febrile infants with pyuria, fever over 48 hours, older age and high CRP related to abnormal acute phase DMSA scan findings regardless urine culture results. Conclusion : 1st or 3rd generation cephalosporins with amikacin could be the first choice of treatment for UTI. Febrile infants with positive urine culture dose mean urinary tract infection but not acute pyelonephritis which directly relates to cortical damage which could be confirmed by acute phase DMSA scan. Even cases with negative urine culture findings, acute pyelonephritis should be concerned in febrile infants with pyuria who are older than 3 months of age, has fever over 48 hours or high CRP level. And in such cases, acute phase DMSA scan and VCUG should be evaluated for early treatment and long term prognosis.

• Childhood Kidney Diseases
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• v.7 no.1
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• pp.30-37
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• 2003

Purpose : $Henoch-Sch\"{o}nlein$ purpura(HSP) is usually a self-limited disease with a good eventual outcome. The prognosis of HSP is mainly determined by the renal involvement. In this study, We evaluated children with biopsy-proven $Henoch-Sch\"{o}nlein$ purpura nephritis about the clinical outcome correlated with renal manifestation and morphologic findings. Methods : The clinical features, initial laboratory and pathologic findings, and clinical out-come were evaluated in 60 children with biopsy-proven $Henoch-Sch\"{o}nlein$ purpura nephritis at Yonsei University Severance Hospital during the period from Jan. 1990 to Dec. 2002. Results : The ratio of male to female patients was 1.2:1. The interval between the onset of $Henoch-Sch\"{o}nlein$ purpura and renal manifestation was less than 3 months in 81% of the patients. Initial renal manifestation was microscopic hematuria in 100% of patients, isolated hematuria in 15%, acute nephritic syndrome in 7%, nephrotic syndrome In 22% of patients. Renal manifestation correlated with clinical outcome. Grade II and III were the most common in histologic grades of ISKDC. Renal pathologic finding correlated with clinical outcome. Conclusion : Renal manifestation and pathologic findings correlated with the clinical out-come. It is necessary to evaluate the correlation between pathologic findings and treatment.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.12 no.2
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• pp.156-162
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• 2009

Purpose: The aim of this study was to investigate the clinical usefulness of upper gastrointestinal (GI) endoscopy in children with Henoch-Sch$\"{o}$nlein purpura (HSP). Methods: We retrospectively analyzed the clinical, endoscopic, and histopathologic records of children with HSP who had been admitted to the Department of Pediatrics of Gil Hospital and underwent upper GI endoscopy between January 2002 and June 2009. Patients were classified into the following two groups for statistical analysis: duodenal involvement (+) and duodenal involvement (-). Results: Fifty-one children with HSP underwent upper GI endoscopy; the mean age was 7.2${\pm}$2.9 years. The upper GI endoscopy showed abnormalities of the duodenum in 38 cases (74.5%), 22 of which had duodenal ulcers. Among the biopsy specimens obtained from the duodenum of 37 cases, 13 cases (35.1%) had leukocytoclastic vasculitis, neutrophil debri, and/or extravasation of RBCs. Steroid use was more frequent in the duodenal involvement (+) group (86.8%) than the duodenal involvement (-) group (53.8%; p=0.02). The mean length of hospitalization was 13.9${\pm}$8.43 days in the duodenal involvement (+) group and 8.1${\pm}$4.62 days in the duodenal involvement (-) group (p=0.003). The recurrence rate was significantly higher in the duodenal involvement (-) group than the duodenal involvement (+) group (p=0.027), whereas none of the other study parameters, such as the age of onset, renal involvement, and steroid use, led to significantly higher or lower recurrence rates. Conclusion: These results suggest that duodenal involvement can influence the clinical course and prognosis of HSP in children.

• Childhood Kidney Diseases
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• v.9 no.2
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• pp.175-182
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• 2005

Purpose : Interleukin 1 receptor antagonist(IL-1ra) is an endogenous antiinflammatory agent that binds to IL-1 receptor and thus competitively inhibits the binding of IL-1$\alpha$ and IL-1$\beta$. Allele 2 in association with various autoimmune diseases has been reported. In order to evaluate the influence of IL-1ra gene VNTR polymorphism on the susceptibility to HSP and its possible association with disease severity, manifested by severe renal involvement and renal sequelae, we studied the incidence of carriage rate and allele frequency of the 2 repeats of IL-1ra allele 2($IL1RN^{*}2$) of the IL-1ra gene in children with HSP with and without renal involvement. Methods : The IL-1ra gene polymorphisms were determined in children with HSP with(n=40) or without nephritis(n=34) who had been diagnosed at Busan Paik Hospital and the control groups(n=163). Gene polymorphism was identified by PCR amplification of the genomic DNA. Results : The allelic frequency and carriage rate of $IL1RN^{*}1$ were found most frequently in patients with HSP and in controls. The allelic frequency of $IL1RN^{*}2$ was higher in patients with HSP compared to that of controls($4.7\%\;vs.\;2.5\%$, P=0.794). The carriage rate of $IL1RN^{*}2$ was higher In patients with HSP compared to that of controls($8.1\%\;vs.\;6.8\%$, P=0.916). The allelic frequency of $IL1RN^{*}2$ was higher in patients with HSP nephritis compared to that of HSP($5.3\%\;vs.\;2.9\%$, P=0.356). The carriage rate of $IL1RN^{*}2$ was higher in Patients with HSP nephritis compared to that of HSP($10.0\%\;vs.\;5.9\%$, P=0.523). Among 13 patients with heavy proteinuria(>1.0 g), 11 had $IL1RN^{*}1$, 1 had $IL1RN^{*}2$ and the others had $IL1RN^{*}4$. At the time of last follow up 4 patients had sustained proteinuria and their genotype was $IL1RN^{*}1$. Conclusion : The allelic frequency and carriage rate of $IL1RN^{*}1$ were found most frequently in patients with HSP and in controls. Our study suggests that the carriage rate and allele frequency of the 2-repeats of IL-1lra allele 2($IL1RN^{*}2$) of the IL-1ra gene may not be associated with susceptibility and severity of renal involvement in children with HSP (J Korean Soc Pediatr Nephrol 2005;9:175-182)

• The Korean Journal of Pharmacology
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• v.31 no.1 s.57
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• pp.95-102
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• 1995

The pathogenesis of diabetic nephropathy is still not completely understood while renal disease is one of the most common disabling complications of diabetes. We, in the present study, investigated the possible involvement of oxidative stress in the development of diabetic nephropathy. To hasten the development of diabetic nephropathy, streptozotocin was injected to unilaterally nephrectomized rats (NEPH-STZ). Eight weeks later, NEPH-STZ rats developed severe hyperglycemia, proteinuria, and hypertension. The kidneys of these rats showed compensatory hypertrophy and mesangial expansion. In contrast, the rats with streptozotocin injection alone (STZ) did not increase urinary protein excretion. Nephrectomized non-diabetic rats (NEPH) developed increased urine protein excretion, but without prominent renal morphological changes. However, oxidation of renal cortical tissue protein significantly increased in all 3 groups of NEPH, STZ and NEPH-STZ in comparison to control rats (CONT). The result indicates the non-specificity of the oxidative tissue damage and suggests that the oxidative damage is hardly a sole mechanism leading to the development of the diabetic nephropathy. However, it would still be a contributing factor considering that the oxidative stress is a common final pathway mediating tissue damages in chronic diabetic complications and other serious illness.

• Childhood Kidney Diseases
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• v.5 no.2
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• pp.213-218
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• 2001

Microscopic Polyangiitis(MPA) belongs to a spectrum of systemic vasculits, and particularly antineutrophil cytoplasmic autoantibodies(ANCA)-associated small-vessel vasculitis which is characterized by involvement of the lung and kidney. The diagnosis of MPA is often difficult to make, and delayed because of the variability of the clinical presentation. Renal biopsies have a very important diagnostic and prognostic value in MPA. We experienced a case of microscopic polyangiits which was confirmed by renal biopsy and positive serum perinuclear ANCA, associated with alveolar hemorrhage and gastrointestinal bleeding. We began methylprednisolone pulse therapy, combined with a low dose of cyclophosphamide and plasmapheresis therapy. ACE inhibitor and Ca channel blocker were used when proteinuria and hypertention developed. On admission, the patient's lab findings showed BUN l17 mg/dL, Cr 2.3 mg/dL, while on the 60th hospital day BUN/Cr values fell to 20.8 mg/dL / 1.6 mg/dL and though proteinuria persisted, the patient's condition was tolerable and is currently under observation on an out-patient basis. The last lab values were BUN 26 mg/dL / Cr 1.6 mg/dL. (J. Korean Soc Pediatr Nephrol 2001 ; 5 : 213-18)

• Childhood Kidney Diseases
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• v.4 no.2
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• pp.111-119
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• 2000

Purpose : Henoch-$Sch{\ddot{o}}nlein$ purpura(HSP) is a common pediatric discase presenting most frequently with skin, gastrointestinal, joint and renal manifestations. The prognosis of HSP is mainly determined by the involvement of the kidney, but prognostic markers have not been established. We evaluated the patients who have HSP nephritis with nephrotic syndrome. Method : Clinical manifestations and laboratory findings were observed and analyzed in 34 cases with HSP which were manifested by nephrotic syndrome hospitalized at Kyung Hee university Hospital during the period from Jan. 1990 to Dec. 1998. Results : 1) Male to female ratio was 1.3:1, and mean age at onset was 8.3 year. 2) Mean duration from symptom onset to renal biopsy was 10.5 weeks. 3) Proportion of patients presenting with acute nephritis was 32.4$\%$, gross hematuria 17.6$\%$, microscopic hematuria 50$\%$. 4) The findings of renal biopsy were 20 cases of grade II, 11 cases of grade III, 2 cases of grade I, 1 case of grade IV according to classification by ISKDC. 5) Patients with grade I were recovered with no residual defect, but patients with grade IV shows active renal disease(states C). Conclusion : Among the 디le patients with Henoch-$Sch{\ddot{o}}nlein$ purpura accompanying nephrotic syndrome, more aggressive treatment might be needed in patients showing crescents formation on renal biopsy. A prospective study will be needed to explore the progression of this disease.