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Background: Congenital nephrotic syndrome (CNS) is characterised by increased proteinuria, hypoproteinemia, and edema beginning in the first 3 months of life. Recently, molecular genetic studies have identified several genes involved in the pathogenesis of CNS. A systematic investigation of the genes for CNS in China has never been performed; therefore, we conducted a mutational analysis in 12 children with CNS,with the children coming from 10 provinces and autonomous regions in China., Methods: Twelve children with CNS were enrolled from 2009 to 2016. A mutational analysis was performed in six children by Sanger sequencing in eight genes (NPHS1, NPHS2, PLCE1, WT1, LAMB2, LMXIB, COQ6 and COQ2) before 2014, and whole-exome sequencing was used from 2014 to 2016 in another six children. Significant variants that were detected by next generation sequencing were confirmed by conventional Sanger sequencing in the patients' families., Results: Of the 12 children, eight patients had a compound heterozygous NPHS1 mutation, one patient had a de novo mutation in the WT1 gene, and another patient with extrarenal symptoms had a homozygous mutation in the COQ6 gene. No mutations were detected in genes NPHS2, PLCE1, LAMB2, LMXIB, and COQ2 in the 12 patients., Conclusions: This study demonstrates that the majority of CNS cases (67%, 8/12 patients) are caused by genetic defects, and the NPHS1 mutation is the most common cause of CNS in Chinese patients. A mutational analysis of NPHS1 should be recommended in Chinese patients with CNS in all exons of NPHS1 and in the intron-exon boundaries.

Background: Idiopathic nephrotic syndrome is the most common glomerular disease in children. This study was undertaken to observe the efficacy and side-effects of rituximab (RTX) in treating children with different types of refractory primary nephrotic syndrome., Methods: Twelve patients with steroid dependent nephrotic syndrome (SDNS), frequently relapsing nephritic syndrome (FRNS), and steroid resistant nephrotic syndrome (SRNS) were enrolled in our study. There were obvious drug side-effects, and proteinuria remained difficult to control. RTX was administered at a dose of 375 mg/m(2) body surface area, once or twice weekly., Results: The male to female ratio was 3:1, and the onset age was 1.6-8.9 years. There were 9 patients with steroid sensitive nephrotic syndrome (SDNS or FRNS), and 3 patients with SRNS. There were 7 patients with minimal change disease (MCD), 3 patients with focal segmental glomerular sclerosis (FSGS), 1 with focal proliferative glomerulonephritis, and 1 without renal biopsy. The total effective treatment rate of RTX was 91.67%, and for 77.78% of the patients, steroid dosage could be reduced. Six months before and after RTX infusion, the mean steroid dosage was significantly decreased (P=0.014) and the recurrence number was significantly reduced (P<0.001). The results were better in MCD patients than in FSGS patients (P=0.045). There was no significant difference between FRNS/SDNS and SRNS patients (P=0.175). During RTX administration, 3 patients developed skin rashes, 1 developed hypotension, and 1 developed a fever. One patient experienced a persistent decrease in serum immunoglobulin level but without serious infection., Conclusion: RTX was effective in the treatment of refractory nephrotic syndrome, and it could significantly reduce the use of steroid and immunosuppressants.

Objective: Recent studies suggest that T cell dysfunction, especially IL-4, may be involved in the pathogenesis of steroid sensitive nephrotic syndrome (SSNS). The aim of this study was to investigate the association between the polymorphisms in variable numbers of tandem repeat region (VTR) of IL-4 gene and childhood SSNS., Method: The polymorphism in the IL-4 gene was identified by using the polymerase chain reaction and direct sequencing methods in 55 Chinese children with SSNS, who were followed-up for at least 1 year, and 115 healthy Chinese adult blood donors as controls. A variable number of tandem repeat (VNTR) region polymorphisms of IL-4 gene were detected, and alleles were designated as IL-4 B1 and B2, corresponding to 2 and 3 repeats, respectively. The serum IgE was also examined in 48 patients before the steroid treatment., Result: (1) There were no significant differences in the genotype and allele frequencies between patients with SSNS and normal controls (P > 0.05). (2) The frequencies of B1B1 (96.4%) were significantly higher in SSNS children with frequent relapses (28 patients had more than 3 relapses during the first year of the disease) than in 27 patients without frequent relapses (P < 0.05). (3) Twenty-three patients with frequent relapses showed higher levels of serum IgE (1.98 +/- 0.23 g/L) than 25 patients (IgE: 1.05 +/- 0.19 g/L) without frequent relapses (P < 0.05), and the patients with B1B1 (38 patients) also had higher serum IgE levels than patients with B1B2 and B2B2 (10 patients) (P < 0.05)., Conclusion: The results suggest that IL-4 VNTR B1B1 genotype might be a predictor for the frequent relapse in childhood SSNS in Chinese.