Twenty-three (88.5%) of the 26 BS patients involved in this study had CLCNKB mutations. The p.W610X mutation and large deletion were two common types of mutations in CLCNKB. The clinical manifestations of BS III were heterogeneous without a genotype-phenotype correlation, typically manifesting cBS phenotype but also aBS or mixed Bartter-Gitelman phenotypes. The molecular diagnostic steps for patients with BS in our population should be designed taking these peculiar genotype distributions into consideration, and a new more clinically relevant classification including BS and Gitelman syndrome is required.

This study retrospectively reviewed the medical records of children with lupus nephritis (LN) who were treated at Seoul National University Children's Hospital from 1986 to 2005 (mean duration 8.3+/-4.4 years). The records of 77 children (22 male and 55 female) were examined. The mean age at diagnosis was 11.9+/-3.0 years. The initial biopsy results revealed a WHO class IV classification for 60 (88.2%) of 68 biopsy proven cases. Of 77 patients, 67 (87.0%) responded initially to the high-dose corticosteroids with or without additional immunosuppressive therapy. Of the initial responders (67), 30 (44.8%) experienced at least one episode of proteinuric (24) or nephritic (6) flare. Thirteen patients (16.9%) progressed to either chronic renal failure (CRF) or end-stage renal disease (ESRD). Six (7.8%) patients died. A Kaplan-Meier estimate of patient survival and CRF-free survival rate was 95.4% and 88.7% at 5 years and 91.8% and 74.7% at 10 years, respectively. Multivariate analysis for class IV LN revealed male gender (P=0.029), initial hypertension (P=0.001) and absence of remission (P=0.002) to be prognostic factors predicting CRF. Glomerulosclerosis of 10% or more (P=0.005), nephritic flare (P=0.011), and presence of anti-phospholipid antibody (P=0.017) or syndrome (P=0.004) were also found to be independent risk factors for CRF. Cyclophosphamide pulse therapy failed to demonstrate superiority over other combined immunosuppressants used for the treatment of diffuse proliferative LN.

Oral steroid treatment is the first line of therapy for childhood nephrotic syndrome (NS). Nonetheless, some patients are resistant to this treatment. Many efforts have been made to explain the differences in the response to steroid treatment in patients with NS based on the genetic background. We have investigated single nucleotide polymorphisms of the MDR1 [C1236T (rs1128503), G2677T/A (rs2032582), and C3435T (rs1045642)] and MIF (G-173C, rs755622) genes in 170 children with NS. Of these children, 69 (40.6%) were initial steroid non-responders, and 23 (13.5% of total) developed chronic kidney disease. Renal biopsy findings, which were available for 101 patients, showed that 35 patients had minimal change lesion and 66 had focal segmental glomerulosclerosis. The frequencies of the MDR1 1236 CC (18.8 vs 7.2%) or TC (53.5 vs 43.5%) genotype and C allele (45.5 vs 29.0%) were significantly higher in the initial steroid responders than in the non-responders. Analysis of MDR1 three-marker haplotypes revealed that the frequency of the TGC haplotype was significantly lower in the initial steroid responders than in the non-responders (15.8 vs 29.0%). There was no association between the MIF G-173C polymorphism and clinical parameters, renal histological findings, and steroid responsiveness. These data suggest that the initial steroid response in children with NS may be influenced by genetic variations in the MDR1 gene.

To review the clinical course and identify prognostic factors, we retrospectively analyzed 92 children with steroid-resistant primary focal segmental glomerulosclerosis (FSGS). The mean age of onset was 80.4+/-42.4 months. The mean follow-up duration was 98.2+/-63.3 months. Eighty-five patients presented with nephrotic syndrome and seven presented with asymptomatic proteinuria. Thirty-three patients were initial responders to steroid treatment (late non-responders) and 59 were initial nonresponders. At last follow-up, 36 patients (39.1%) were in complete remission, and 29 (31.5%) progressed to chronic renal failure (CRF). Renal survival rates at 5, 10, and 15 years were 84, 64, and 53%, respectively. By morphological classification, there were tip variants (6.1%), collapsing variants (10.6%), cellular variants (1.5%), perihilar variants (9.1%), and NOS (not otherwise specified, 72.7%). Among the variants, there were no significant differences in age of onset, degree of proteinuria, response to treatment, or progression to CRF. Poor prognostic factors for CRF included: asymptomatic proteinuria at presentation, initial renal insufficiency, higher segmental sclerosis (%), severe tubulointerstitial change, initial nonresponse, and absence of remission. In the multivariate analysis, an increase in the initial serum creatinine and resistance to treatment were independent risk factors for CRF. A more prolonged use of corticosteroid therapy and early introduction of cyclosporin A (CsA) may improve the prognosis for primary FSGS in patients with initial steroid nonresponsiveness.

The Wilms tumor suppressor gene, WT1, plays an important role in the development of the urogenital system and the gonads, and clinical syndromes associated with WT1 mutations, such as WAGR syndrome, Denys-Drash syndrome and Frasier syndrome, typically manifest as renal and genitourinary abnormalities. WT1 may also play an important role in the development of the diaphragm, and recently several papers have reported an association between WT1 mutations and diaphragmatic hernias. In addition, WT1 mutations were also detected in some patients with Meacham syndrome, a rare malformation syndrome comprising congenital diaphragmatic hernia, double vagina, sex reversal, and cardiac malformations. Here, we report a case of an infant with typical clinical features of Deny-Drash syndrome and a heterozygous missense mutation, Arg366His, in the WT1 gene, in whom a diaphragm defect was detected after starting peritoneal dialysis. Diaphragmatic defects are rare but may be considered as clinical manifestations of WT1 mutation syndromes. In addition, we suggest that WT1 abnormalities should be suspected in patients with chronic renal failure who develop hydrothorax after peritoneal dialysis, especially in those with genitourinary abnormalities.