Ichiro Kamioka

Risk factors for developing severe clinical course in HUS patients: a national survey in Japan

Background: Hemolytic uremic syndrome (HUS) is characterized by acute renal failure, thrombocytopenia and hemolytic anemia. Cases accompanied by prodromal gastrointestinal tract symptoms are referred to as typical HUS. Some severe HUS patients require dialysis or develop central nervous system (CNS) disorders after the onset of HUS.

Management of diarrhea-associated hemolytic uremic syndrome in children

Most cases of diarrhea-associated hemolytic uremic syndrome (D+HUS) are caused by Shiga toxin-producing bacteria. Shiga toxin-producing Escherichia coli (STEC) O157:H7 has the strongest association worldwide with HUS. A massive outbreak of E. coli O157:H7 infections in Sakai, Osaka, Japan, in 1996 raised public and medical awareness of STEC. However, most cases are sporadic or occur in small clusters. Indeed, more than 100 sporadic or small cluster cases of D+HUS occur every year in Japan. The use of antibiotics in patients with definite or possible enteric STEC infections is controversial; however, there has been no randomized controlled trial to date showing the effectiveness of antibiotics for the prevention of the development of HUS. Thus, most investigators in western countries believe that antibiotics should not be administered to patients with such infections, and the management of HUS remains supportive. There are no specific therapies to ameliorate the course of the disease, and vascular injury leading to HUS is likely to be well under way by the time infected patients seek medical attention for diarrhea. The best way to prevent HUS is to prevent primary infection by Shiga toxin-producing bacteria.

Familial Cases of Periodic Fever with Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome

We report three familial cases of periodic fever with aphthous stomatitis, pharyngitis, and cervical adenitis syndrome, including a pair of monozygotic twins and their mother. It suggests that periodic fever with aphthous stomatitis, pharyngitis, and cervical adenitis syndrome may have a certain monogenetic background.

Detection of a transcript abnormality in mRNA of the SLC12A3 gene extracted from urinary sediment cells of a patient with Gitelman's syndrome

To date, many mutations, including intronic nucleotide changes, in the SLC12A3 gene encoding the thiazide-sensitive sodium-chloride cotransporter (NCCT) have been reported in Gitelmans syndrome (GS) patients. However, it has not been clarified whether intronic nucleotide changes affect mRNA content. Since mRNA analysis is possible only after obtaining renal biopsy specimens, no studies have been conducted to identify transcript abnormalities in GS. In the study reported here, we investigated such transcript abnormalities for the first time by using mRNA expressed in a patients urinary sediment cells. Direct sequencing analysis of leukocyte DNA disclosed one known missense mutation (R399C) and one known nucleotide change of the splicing acceptor site of intron 13 (1670-1 g > t). mRNA extracted from the urinary sediment cells was analyzed by RT-PCR to determine the pathogenic role of the intron mutation. A fragment encompassing exon 13 to 15 was amplified as two products, one consisting of all three exons and the other lacking only exon 14 in its entirety. Our investigation was the first to demonstrate exon 14 skipping in an NCCT transcript in renal cells. This methodology thus constitutes a potential noninvasive analytical tool for every inherited kidney disease.

High-dose mizoribine treatment for adolescents with systemic lupus erythematosus

Background: In treating pediatric patients with systemic lupus erythematosus (SLE), it is necessary to quickly attain remission to avoid sequelae in various organs and to maintain it over a long period. However, to maintain remission, the prolonged use of immunosuppressants which have various adverse effects, is often necessary in addition to steroids, and complications due to such immunosuppressants pose very important problems. A regimen of mizoribin (MZR) at 150 mg/day divided into two or three doses has been recommended, but while this regimen has been safe, its efficacy has not been satisfactory. However, MZR produces effects dose‐dependently, and the dose recommended to date may have been insufficient for the treatment of children with SLE.

Prognosis and pathological characteristics of five children with non-Shiga toxin-mediated hemolytic uremic syndrome

Background: The three major signs of hemolytic uremic syndrome (HUS) are hemolytic anemia, thrombopenia and acute renal failure. HUS is classified into Shiga toxin‐mediated HUS (Stx‐HUS) and non‐Shiga toxin‐mediated HUS (nStx‐HUS). The prognosis of nStx‐HUS is reported to be less favorable than that of Stx‐HUS. Although the association between the prognosis and pathological characteristics of HUS have been reported such that the prognosis was considered to be poor for thrombotic microangiopathy (TMA) with predominant arterial involvement (arterial TMA), good for TMA with predominant glomerular involvement (glomerular TMA) and dependent on the extent of necrosis in cases of renal cortical necrosis, it is not yet clear whether pathological findings are also related to the renal prognosis of nStx‐HUS cases. Therefore the purpose of the present paper was to analyze renal biopsy findings and prognosis for five children with nStx‐HUS.

A case of anti-GA1 antibody-positive Fisher syndrome with elevated tau protein in cerebrospinal fluid.

We describe a boy with Fisher syndrome. He presented the typical symptoms of Fisher syndrome, including external ophthalmoplegia, abnormality of convergence, and areflexia, after an episode of Campylobacter enterocolitis. Atypically, however, anti-GA1 antibody was detected in his serum, though anti-GQ1b and anti-GT1a antibodies were not. In addition, the tau protein level in his cerebrospinal fluid was elevated. Generally, Fisher syndrome is a self-limiting disease and has a good prognosis. In our patient, however, mild diplopia and areflexia persisted 6 months after their onset. Here, we report on the first Fisher syndrome patient with anti-GA1 antibody in the serum and elevated tau protein in the cerebrospinal fluid.

Long-term follow-up of juvenile acute nonproliferative glomerulitis (JANG)

This report concerns a 9-year-old boy who was diagnosed with atypical type II membranoproliferative glomerulonephritis and later proved to have juvenile acute nonproliferative glomerulitis (JANG). To the best of our knowledge, this is the first report on the long-term clinical and pathological follow-up of JANG.

Clinicopathological characteristics and renal outcomes of childhood-onset lupus nephritis with acute kidney injury: a multicenter study

Abstract Objectives: Acute kidney injury (AKI) at onset of adult systemic lupus erythematosus (SLE) is a risk factor for end stage kidney disease (ESKD). However, data on childhood-onset lupus nephritis (LN) with AKI are scarce. Methods: We retrospectively reviewed the complete files of pediatric SLE patients from 1995 to 2010. All patients underwent kidney biopsy promptly after diagnosis. Results: Thirty-six patients (10 males and 26 females) were enrolled. Mean age at diagnosis and observation period were 11.6 ± 2.4 and 8.1 ± 4.4 years, respectively. Seven patients had AKI at onset of SLE. Compared with those without AKI, patients with AKI had significantly higher proportions of pathologically proliferative LN. Only one patient with AKI progressed to ESKD without complete recovery of renal function. Overall and renal survival rates were 100and 97.2%, respectively. There was no significant difference in estimated glomerular filtration rate at the final visit (85ml/min/1.73 m2 in the AKI group vs. 103.2 ml/min/1.73 m2 in the non-AKI group; p = .11). Conclusion: Our study demonstrated favorable renal outcomes in childhood-onset LN with AKI in the near to midterm period. Inducing complete remission may be important for preserving renal function.