Rieko Nagaoka

Apoptosis of renal tubular cells in Shiga-toxin-mediated hemolytic uremic syndrome.

In order to clarify the mechanism of unusual renal tubular dysfunction seen in a child with Shiga toxin (Stx)-mediated hemolytic uremic syndrome (HUS), we studied the renal biopsy specimens for Stx binding and apoptosis of renal tubular cells. A 7-year-old boy with Stx-2-mediated HUS demonstrated extensive renal tubular damage characterized by nonoliguric acute renal failure, increased urinary tubular enzymes and defective urine-concentrating capacity. His renal biopsy specimens were analyzed for Stx binding and apoptotic cell death. Seven kidney tissue specimens obtained from patients without HUS served as controls. Detection of Stx binding to renal sections and apoptotic cells were performed using mouse monoclonal anti-Stx 2 antibody and the TUNEL method, respectively. Positive staining was observed predominantly in renal tubular cells, while the 7 kidney tissue specimens from control patients did not show positive staining. To the best of our knowledge, this is the first case to show Stx binding and apoptotic cell death in renal tubules on biopsy specimens obtained from a child with Stx-mediated HUS. In conclusion, this case suggests that vascular endothelial cells are not the sole nor the consistent target for Stx-mediated cell injury and that significant renal tubular damage other than glomerular damage might occur in some children with Stx-mediated HUS.

Angiotensin converting enzyme gene polymorphism in primary vesicoureteral reflux

Abstract  We studied the insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene in 78 patients with primary vesicoureteral reflux (VUR), and examined renal function by dimercaptosuccinate (DMSA) renoscintigraphy and diethylenetriaminepenta-acetic acid (DTPA) renogram in each genotype. Patients were classified into three genotypes according to the ACE gene I/D polymorphisms: 32 in II genotype, 36 in ID, and 10 in DD. The incidence of presumably congenital unilateral small kidneys was high in DD patients (70%). Glomerular filtration rate obtained from DTPA renogram was 120.7±35.7 ml/min (expressed as mean±SD) in II genotype, 111.7±33.3 in ID, and 88.0±18.0 in DD. The total quantitative DMSA tracer uptake of both kidneys was also low in patients with the D allele. This study shows that the D allele of ACE gene is closely related to small congenital kidneys with refluxing ureters in patients with primary VUR, and in accordance with previous reports, this allele is also related to the progression of reflux nephropathy.

Mizoribine treatment for childhood IgA nephropathy

Background : There is currently no established therapy for childhood IgA nephropathy (IgAN). Mizoribine, a newly developed immunosuppressive agent characterized as a safe and well‐tolerated drug, has been widely used in diverse conditions. Our preliminary study demonstrated that mizoribine could reduce the amount of proteinuria in children with IgAN. The present study was conducted to confirm this finding.

Non-lupus nephropathy associated with antiphospholipid antibodies.

Abstract Renal biopsy was performed in a 12-year-old girl with hematuria and proteinuria which was first detected at the age of 7, and the findings were the mesangial proliferative glomerulonephritis with IgG and C3 deposits. The routine blood examination for the biopsy disclosed the presence of the prolonged activated partial thromboplastin time and the biological false positive reaction in the syphilis test. These results led us to the further investigation, which revealed the presence of high titers of anticardiolipin antibodies. Since this girl presented no extra-renal symptoms of systemic lupus erythematosus (SLE) and had negative serologic tests for SLE, we hypothesize that her nephritis is closely related to antiphospholipid antibodies.

Effect of Mizoribine on IL-6 Release by Peripheral Blood Mononuclear Cells

Background/Aim: A novel immunosuppressant, mizoribine (MZB), has recently been reported to be effective in the treatment of IgA nephropathy (IgAN), although its mechanism of action remains unknown. This study was conducted to investigate whether the efficacy of MZB on IgAN is exerted by suppression of interleukin-6 (IL-6) release. Methods: Peripheral blood mononuclear cells (PBMC) were collected from 4 children with IgAN (median age 13.0 years) and 4 control children (median age 5.2 years). PBMC were cultured with medium alone or medium with lipopolysaccharide (LPS), and then incubated with LPS and MZB. Culture supernatants were assayed for lL-6. Results: IL-6 release was increased by LPS in all subjects. Although the median value was higher in IgAN patients (median increase in IL-6 release 1,298.1%) than in controls (median 489.2%), statistical significance was not reached (p > 0.05). 10 mg/ml of MZB suppressed the release of IL-6 in both IgAN patients (median decrease in IL-6 release 39.3%) and controls (median 43.2%), with statistical significance (p < 0.05 and p < 0.01, respectively). Conclusion: This study suggests that MZB could suppress IL-6 release in vitro and thus may exert its efficacy on IgAN.