• Childhood Kidney Diseases
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• v.25 no.1
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• pp.14-21
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• 2021

Chronic kidney disease, the presence of structural and functional abnormalities in the kidneys, is associated with a lower quality of life and increased morbidity and mortality in children. Genetic etiologies account for a substantial proportion of pediatric chronic kidney disease. With recent advances in genetic testing techniques, an increasing number of genetic causes of kidney disease continue to be found. Genetic testing is recommended in children with steroid-resistant nephrotic syndrome, congenital malformations of the kidney and urinary tract, cystic disease, or kidney disease with extrarenal manifestations. Diagnostic yields differ according to the category of clinical diagnosis and the choice of test. Here, we review the characteristics of genetic testing modalities and the implications of genetic testing in clinical genetic diagnostics.

• Clinical and Experimental Pediatrics
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• v.52 no.11
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• pp.1260-1266
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• 2009

Purpose : Idiopathic nephrotic syndrome (NS) can be clinically classified as steroid-sensitive and steroid-resistant. The detailed mechanism of glucocorticoid action in NS is currently unknown. Methods : In this study, we investigated 3 known single nucleotide polymorphisms (SNPs) (ER22/23EK, N363S, and BclI) of the glucocorticoid receptor gene (the NR3C1 gene) in 190 children with NS using polymerase chain reaction-restriction fragment length polymorphism and analyzed the correlation between the genotypes and clinicopathologic features of the patients. Results : Eighty patients (42.1%) were initial steroid nonresponders, of which 31 (16.3% of the total) developed end-stage renal disease during follow-up. Renal biopsy findings of 133 patients were available, of which 36 (31.9%) showed minimal changes in NS and 77 (68.1%) had focal segmental glomerulosclerosis. The distribution of the BclI genotypes was comparable between the patient and control groups, and the G allele frequencies in both the groups were almost the same. The ER22/23EK and N363S genotypes were homogenous as ER/ER and NN, respectively, in all the patients and in 100 control subjects. The BclI genotype showed no correlation with the NS onset age, initial steroid responsiveness, renal pathologic findings, or progression to end-stage renal disease. Conclusion : These data suggested that the ER22/23EK, N363S, and BclI SNPs in the NR3C1 gene do not affect the development of NS, initial steroid responsiveness, renal pathologic lesion, and progression to end-stage renal disease in Korean children with NS.

• Childhood Kidney Diseases
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• v.3 no.1
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• pp.48-56
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• 1999

Purpose : This multicenter collaboratory study was conducted to see the therapeutic efficacy and side effect of cyclosporine A (Cipol-$N^{(R)}$, Chong Kun Dang) on children with idiopathic nephrotic syndrome who experienced frequently relapsing (FR), steroid dependent (SD), or steroid resistant (SR) pattern. Patients and methods : Thirty-nine children with SD/FR NS and 3 children with SR NS were enrolled in the study. After induction of remission (SD/FR NS) with steroid or after 4 weeks of steroid therapy (SR NS), cyclosporine A was started in a dose of 4-5 mg/Kg/day in two divided dose and steroid (prednisolone or equivalent dose of deflazacort) was tapered slowly. During 16 weeks of study period, monthly check up of physical examination and various laboratory tests including BUN, creatinine, Ccr and cyclosporine blood level were done. Results : Out of 39 children with SD/FR NS, 35($89.7\%$) maintained sustained remission and at 4 weeks after therapy, values of serum protein, albumin, cholesterol, and 24 hours urinary protein excretion showed normal values. Two out of 3 children with SR NS showed and sustained remission with cyclosporine A therapy. Side reaction to cyclosporine A therapy showed hypertrichosis in 8 cases and hyperuricemia in 5 cases. However, other laboratory tests including CBC, liver profile, BUN, creatinine and GFR (creatinine clearance utilizing 24 hour urine) did not show any abnormalities during the 16 weeks of study period. Conclusion : Cyclosporine A (Cipoi-$N^{(R)}$ Chong Kun Dang) can be utilized quite effectively on children with SD/FR or SR NS and further trial of cyclosporine A on long-term basis (1-2 year period) is needed to determine it's efficacy and side effect (especially nephrotoxicity) of long-term administration of cyclosporine A.

• Clinical and Experimental Pediatrics
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• v.59 no.5
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• pp.242-245
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• 2016

Thromboembolic complications (TECs) are clinically important sequelae of nephrotic syndrome (NS). The incidence of TECs in children is approximately 2%-5%. The veins are the most commonly affected sites, particularly the deep veins in the legs, the inferior vena cava, the superior vena cava, and the renal veins. Arterial thrombosis, which is less common, typically occurs in the cerebral, pulmonary, and femoral arteries, and is associated with the use of steroids and diuretics. Popliteal artery thrombosis in children has been described in cases of traumatic dissection, osteochondroma, Mycoplasma pneumoniae infection, and fibromuscular dysplasia. We report of a 33-month-old girl with bilateral iliac and popliteal arterial thrombosis associated with steroid-resistant NS due to focal segmental glomerulosclerosis. Her treatment involved thrombectomy and intravenous heparinization, followed by oral warfarin for 8 months. Herein, we report a rare case of spontaneous iliac and popliteal arterial thrombosis in a young child with NS.

• Childhood Kidney Diseases
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• v.2 no.2
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• pp.110-117
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• 1998

Purpose : Henoch-$Sch{\ddot{o}}nlein$ purpura nephritis(HSPN) accompanied by nephrotic syndrome(NS) is known to have a poor prognosis and effective treatment is still controversial, even though both corticosteroids and immunosuppresant have been used for therapy. Cyclosporine A(CsA) is a well known immunosuppresant and widely used in renal transplantation and glomerular diseases especially steroid resistant. The aims of this study was to evaluate the therapeutic effect of CsA and to compare CsA with previously reported our data of rifampin(RFP) and azathioprine(AZA) in children with HSPN accompanied by NS. Methods : 37 HSPN patients with NS confirmed by renal biopsy were selected. Of these, 17 patients were treated with CsA(5 mg/kg/day) fur 6-8 months, 7 children were treated with RFP(10-20 mg/kg/day) for 9-12 months and 13 patients were treated with AZA(2 mg/kg/day) fur 8 months. Along with these regimens, low dose oral prednisolone(0.5-1 mg/kg, qod) was also used. Sequential renal biopsy was done in all patients 1 month after termination of treatment. Results : Complete remission rate of nephrotic syndrome was $58.8\%$ in CsA, $57.1\%$ in RFP and $38.4\%$ in AZA group after 17, 22, 11 months of mean follow-up period. Overall remission rate including partial remission was $88.2\%$ in CsA, $85.7\%$ in RFP and $84.6\%$ in AZA group. Disappearance rate of hematuria was $58.8\%$ in CsA, $57.1\%$ in RFP and $46.2\%$ in AZA group. Improvement of grade of clinical status was observed in 17 out of 17 CsA, 7 out of 7 RFP and 10 out of 13 AZA group. Improvement of pathologic class on sequencial renal biopsy was shown in 5 CsA($29.4\%$), none RFP($0\%$) and 2 AZA group($12.4\%$). Improvement on histologic immune-deposition was seen in 15 CsA($88.2\%$), 6 RFP($85.9\%$) and 4 AZA group($30.8\%$). Conclusion : In conclusion, Both CsA and RFP treated groups showed better result in complete remission rate of nephrotic syndrome and significant improvement of histologic immune-deposition compared with AZA treated group(p=0.004). So, we recommend CsA and REP rather than AZA for immunosuppresant treatment in HSPN with nephrotic syndrome.

• Childhood Kidney Diseases
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• v.3 no.2
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• pp.130-144
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• 1999

Purpose : Long-term use of Cyclosporine(CsA) reduce renal blood flow by afferent arteriolar vasoconstriction and lead to chronic pathologic changes of CsA nephrotoxicity - 1) interstitial nephritis(IN); tubular atrophy (TA) and/or interstitial fibrosis(IF),2) arteriolopathy(AP). The Object of this study is to estimate the incidence of chronic pathologic CsA nephrotoxicity by duration of treatment and type of renal disease, relationship between histologic and clinical nephrotoxicity, and optimal duration of CsA therapy. Methods : 102 children with steroid resistant or dependent nephrotic syndrome confirmed by renal biopsy and treated with CsA from 1986 to 1997 were enrolled in this study(58 MCNS, 10 FSGS, 10 MGN, 15 $Henoch-Sch\"{o}nlein$ purpura nephritis with nephrotic syndrome (HSPN) and 9 IgA nephropathy with nephrotic syndrome(IgAN)). CsA was administered for 1yr, 1.5yr, 2yr in 24, 12, 22 MCNS patients and 2, 2, 6 FSGS patients respectively, 1yr, 2yr in MGN and 1yr in HSPN and IgAN. Sequential biopsies were done in all 102 patients after CsA treatment for evaluation of pathologic nephrotoxicity. Results : Complete remission rate was 92.2% (100% in MCNS and MGN, 80% in FSGS, 86.6% in HSPN and 55.5% in IgAN). Incidence of relapse during 6months after CsA treatment was significantly decreased compaed with relapsing spisodes during 6months before CsA treatment in MCNS(P<0.0001) and FSGS(P<0.0001). According to pathologic changes, 71 patients(69.6%) showed no pathological change, 24 patients(23.5%) showed IN and 7 patients(6.8%) showed AP. IN was 16.6%, 33.3%, 27.2% in 1, 1.5, 2 year of CsA treatment group in MCNS. AP was 0%, 16.6%, 9% in 1, 1.5, 2 year of CsA treatment group in MCNS. 14 out of 58 MCNS(24.1%) showed IN and 4 out of 58 MCNS(6.8%) showed AP. Incidence of pathologic change was significantly lower in CsA therapy of <1yr than >1yr(P=0.03). There were no significant difference of incidence of pathologic change in original renal disease, age and sex. Conclusion : Duration of CsA treatment was significant risk factor for nephrotoxicity and optimal duration seemed to be 1 year. Pathologic change due to nephrotoxicity did not correlate with deterioration of renal function and only detectable by renal biopsy.