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

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.

A case of microscopic polyangiitis with skin manifestations in a seven-year-old girl.

A case of a 7-year-old girl with microscopic polyangiitis (MPA) with a skin eruption characterized by maculopapular, erythematous and purpuric lesions on the face, elbows, and knees is presented. Anti-neutrophil cytoplasmic autoantibodies (ANCA) with myeloperoxidase specificity (MPO-ANCA) were identified. Chest X-ray and computed tomography scan revealed diffuse infiltrates in both lung fields, suggesting alveolar hemorrhage. Microscopic hematuria was detected but a renal biopsy showed no abnormalities. Histological examination of a skin biopsy from a purpuric papule showed leukocytoclastic vasculitis of the small vessels in the entire dermis. The patient was treated with prednisolone and mizoribine, resulting in an improvement in the skin lesions except for those on the knee.

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.

Treatment strategies for Henoch-Schönlein purpura nephritis by histological and clinical severity.

The management of Henoch-Schönlein purpura nephritis (HSPN) is controversial. It has been revealed that some patients develop end-stage renal disease and aggressive treatment with drugs such as steroids is increasing, and some of them may be overzealous. At our institutes, our treatment decisions are based on the clinical and pathological severity of the case in an attempt to limit the indications for aggressive therapies such as steroids and immunosuppressive agents. Here, we retrospectively examined the efficacy of treatment for HSPN. Renal biopsy was performed in patients with nephrotic syndrome or persistent proteinuria for more than 3 months and patients were classified by treatment. Patients (n=31) with moderately severe HSPN (histological grade I-III and serum albumin [Alb] >2.5 g/dl) were treated with angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers. Patients (n=19) with HSPN exceeding grade III or Alb ≤ 2.5 g/dl received combination therapy comprising prednisolone, immunosuppressants, warfarin, and dipyridamole. All patients showed resolution of proteinuria without renal dysfunction during the observation period (3.76 ± 0.37 years). Our findings support those of some earlier reports that treatment strategies for HSPN should depend on the histological and clinical severity. Furthermore, aggressive therapies, particularly combination therapies, are unnecessary for moderate-severe HSPN.

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.

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.

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. METHODS: Patients who developed typical HUS in 2001 and 2002 in Japan, 127 in all, were the study subjects. To identify the risk factors for the development of a severe clinical course, clinical and laboratory data were analyzed on logistic regression. RESULTS: Two of the 127 patients died (1.6%): one from acute cardiac failure and the other from a CNS disorder. Thirty-five patients required dialysis (28%) and 30 had CNS symptoms (24%). Multivariate analysis indicated that the risk factors for need for dialysis were serum sodium and alanine aminotransferase (ALT) levels of /=70 IU/L, respectively, at the onset of HUS and those for developing CNS disorders were dialysis and C-reactive protein (CRP) >/=5.0 mg/dL at the onset of HUS. CONCLUSIONS: Because patients with these risk factors, such as low serum sodium, high ALT or high CRP levels, may require dialysis or develop CNS disorders, they should be treated carefully in the early stage of HUS.

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.

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. METHODS: Clinical records of five cases of nStx-HUS among 74 cases of diagnosed HUS were reviewed, and information and data were summarized. RESULTS: Histological examination of the kidney led to the diagnosis of arterial TMA in three cases, and glomerular TMA and severe renal cortical necrosis in one case each. Analysis of the relationship between renal histological findings and the prognosis found that three patients with arterial TMA and one patient with severe renal cortical necrosis later developed end-stage renal failure while one patient with glomerular TMA has continued to show normal renal function. CONCLUSIONS: These findings indicate that pathological findings are closely related to the prognosis in cases of nStx-HUS.

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 Gitelman's 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 patient's 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. METHODS: The authors administered oral MZR at 300 mg/day in two divided doses, which is twice the conventional dose for adults, to five adolescents with SLE. Three of these five were markedly steroid-dependent patients and two had previously been treated with steroids only. Thereafter, the authors evaluated the safety and efficacy of the regimen by following the patients for at least 7 months after the beginning of treatment. RESULTS: Patients 1 and 2 had been treated with prednisolone (PSL) and cyclosporine (CyA), but as the duration of CyA administration became long, it was replaced with 300 mg MZR. This transition could be accomplished smoothly. Patient 3 showed repeated recurrence during the treatment with PSL and CyA or CPM, but the symptoms could be controlled by the addition of 300 mg MZR. In patients 4 and 5, the control of symptoms with PSL alone was judged to be difficult, and concomitant administration of MZR at 300 mg was started. This resulted in a decrease in the dose of PSL. The Cmax (C2) of MZR was 1.33 microg/mL or higher in all five patients, and the efficacy of the treatment was satisfactory. Concerning side-effects, hyperuricemia was noted in two patients, but it was resolved in one of them by reducing the dose of MZR and in the other spontaneously while the treatment was continued. Temporary exacerbation of hair loss was observed in two patients, but it disappeared in both of them after a few months. CONCLUSION: MZR could be administered at a high dose effectively and safely. However, monitoring of the serum uric acid level was necessary. High-dose MZR therapy showed an efficacy and safety that would warrant its application to steroid-dependent pediatric patients with SLE.

Long-term follow-up of atypical membranoproliferative glomerulonephritis: are steroids indicated?

Atypical membranoproliferative glomerulonephritis (MPGN) has been reported to have a good prognosis when treated with corticosteroids. However, this recommendation is based on uncontrolled trials and is associated with many complications. The purpose of our study is to determine whether steroid therapy is indicated for atypical MPGN. The cases of seven patients with atypical MPGN are reported in this study. Urinary abnormalities of five of them were detected by urine screening at school, of two because of macrohematuria. Hypocomplementemia was noted in six patients. All but one patient were treated without corticosteroids, and five with angiotensin-converting enzyme inhibitors (ACEI) and/or the Chinese herbal medicine Sairei-to (TJ-114). One patient recovered spontaneously from proteinuria and was therefore not treated, and one who developed severe proteinuria during observation was treated with corticosteroids. After an average follow-up period of 10.0 years, five patients showed normal urinary findings, one had hematuria and one proteinuria. At the most recent follow-up, the renal function of all patients remained within the normal range, and serum C3 had returned to normal levels in five out of six. These findings suggest that the indication of steroid therapy for atypical MPGN should be re-examined, since most of the patients with atypical MPGN seem to have an excellent prognosis without treatment with corticosteroids.