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ABSTRACT: The renal prognosis of patients with Wilms' tumor, aniridia, genitourinary anomalies, and mental retardation syndrome (WAGR) is poor. However, the renal histology and its mechanisms are not well understood. We performed renal biopsies in 3 patients with WAGR syndrome who had heavy proteinuria. The complete deletion of one WT1 allele was detected in each patient by constitutional chromosomal deletion at 11p13 using G-banding, high-resolution G-banding, and fluorescence in situ hybridization. The patients exhibited proteinuria at the ages of 6, 10, and 6 years and were diagnosed as having focal segmental glomerulosclerosis (FSGS) at the ages of 7, 16 and 19 years, respectively. They exhibited normal or mildly declined renal function at the time of biopsy. Re-examination of a nephrectomized kidney from 1 patient revealed that some glomeruli showed segmental sclerosis, although he did not have proteinuria at the time of nephrectomy. The other 2 patients did not develop Wilms' tumor and thus did not undergo nephrectomy, chemotherapy, or radiotherapy, thereby eliminating any effect of these therapies on the renal histology. In conclusion, complete deletion of one WT1 allele may induce the development of FSGS. Our findings suggest that haploinsufficiency of the WT1 could be responsible for the development of FSGS.
PEDIATRICS 05/2012; 129(6):e1621-5. · 4.47 Impact Factor
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ABSTRACT: We report a case of a 2-year-old boy with steroid- and ciclosporin (CsA)-resistant collapsing focal segmental glomerulosclerosis (FSGS) who went into complete remission with a combination of IV rituximab and methylprednisolone pulse therapy (MPT) while receiving oral CsA. He was initially treated with steroids including MPT, CsA, and plasmapheresis, but his massive proteinuria and severe systemic edema persisted. We treated him with four weekly doses of intravenous rituximab. After the second administration of rituximab, his proteinuria and systemic edema were dramatically improved, but hypoalbuminemia and proteinuria persisted. Eight months after the onset, he was re-treated with two courses of MPT. Thereafter, he finally went into complete remission 1 month after MPT. He continued in remission for 8 months with CsA, but then relapsed. However, he went into complete remission again with 60 mg/m(2) of oral prednisolone without rituximab and since then, he has been in remission with CsA. This is the first report of the successful treatment of collapsing FSGS with rituximab. Thus, rituximab emerges as a new therapeutic option against refractory collapsing FSGS.
Pediatric Nephrology 05/2010; 25(5):957-9. · 2.52 Impact Factor
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ABSTRACT: Type I Bartter syndrome (BS) is caused by mutations of the Na-K-2Cl cotransporter (NKCC2)-encoding SLC12A1 gene. The clinical phenotype of this severe form of BS is characterized by polyhydramnios, premature delivery, failure to thrive, and nephrocalcinosis, and the diagnosis is usually made during the antenatal-neonatal period. This report concerns a 29-year-old Japanese man with atypical type I BS due to a compound heterozygous mutation of the SLC12A1 gene. He was born after full-term pregnancy complicated by polyhydramnios. He first presented with asymptomatic proteinuria at the age of 20 years and was diagnosed with BS based on laboratory data. There were signs of moderate proteinuria, mild renal dysfunction and nephrocalcinosis. Renal biopsy showed focal segmental glomerulosclerosis (FSGS), and genetic testing revealed novel mutations of A555V and G809V in the SLC12A1 gene. The patient's sister showed the same clinical course, laboratory test abnormalities and gene mutations. Our patient had a type I BS with an atypical clinical course, which was diagnosed when he was 20 years old. Laboratory findings indicated phenotypic variability in this disease, and the presence of nephropathy suggested that FSGS might be one of the lesions causing end-stage renal failure in this disease.
Pediatric Nephrology 11/2008; 24(2):415-8. · 2.52 Impact Factor
