Although hyponatremia frequently occurs in Kawasaki disease (KD), the clinical characteristics of KD patients with hyponatremia and the pathogenesis of hyponatremia in KD remain unknown. The aims of this study were to define the clinical characteristics of KD patients with hyponatremia (serum sodium <135 mEq/l) and to determine the factors associated with its development. One hundred and fourteen patients with KD were included in this study. Fifty-one patients (44.7%) had hyponatremia. Coronary artery lesions and dehydration were significantly more common in patients with hyponatremia. The duration of fever was significantly longer in patients with hyponatremia. Pyuria and hematuria were present significantly more often in patients with hyponatremia. The serum concentrations of potassium, chloride and total cholesterol were significantly lower in patients with hyponatremia. Serum C-reactive protein and alanine aminotransferase were significantly higher in patients with hyponatremia. Some patients with pyuria and hyponatremia exhibited increased excretion of urinary tubular epithelial cells and urinary casts. There was no difference in the incidence of diarrhea between patients with hyponatremia and patients without hyponatremia. These results indicate that hyponatremia in KD occurs in patients exhibiting severe inflammation. Further studies will be necessary to confirm the pathogenic mechanisms of hyponatremia in patients with KD.

Since vasculitis following influenza vaccination has been only rarely reported, routine influenza vaccination should not be restricted. However, caution should be required when patients with small vessel vasculitis, especially with ANCA-associated vasculitis following influenza vaccination or with post-influenza vaccination-reactivated IgA vasculitis, receive influenza vaccination again.

B-type ephrins are membrane-bound proteins that maintain tissue function in several organs. We previously reported that ephrin-B1 is localized at the slit diaphragm of glomerular podocytes. However, the function of ephrin-B1 at this location is unclear. We analyzed the phenotype of podocyte-specific ephrin-B1 knockout mice and assessed the molecular association of ephrin-B1 and nephrin, a key molecule of the slit diaphragm, in HEK293 cells and rats with anti-nephrin antibody-induced nephropathy. Compared with controls, ephrin-B1 conditional knockout mice displayed altered podocyte morphology, disarrangement of the slit diaphragm molecules, and proteinuria. Ephrin-B1 expressed in HEK293 cells immunoprecipitated with nephrin, which required the basal regions of the extracellular domains of both proteins. Treatment of cells with an anti-nephrin antibody promoted the phosphorylation of nephrin and ephrin-B1. However, phosphorylation of ephrin-B1 did not occur in cells expressing a mutant nephrin lacking the ephrin-B1 binding site or in cells treated with an Src kinase inhibitor. The phosphorylation of ephrin-B1 enhanced the phosphorylation of nephrin and promoted the phosphorylation of c-Jun N-terminal kinase (JNK), which was required for ephrin-B1-promoted cell motility in wound-healing assays. Notably, phosphorylated JNK was detected in the glomeruli of control mice but not ephrin-B1 conditional knockout mice. In rats, the phosphorylation of ephrin-B1, JNK, and nephrin occurred in the early phase (24 hours) of anti-nephrin antibody-induced nephropathy. Through interactions with nephrin, ephrin-B1 maintains the structure and barrier function of the slit diaphragm. Moreover, phosphorylation of ephrin-B1 and, consequently, JNK are involved in the development of podocyte injury.

The 1997 to 2001 influenza A epidemics in Japan were markedly neurovirulent, and many children died of influenza-associated encephalitis/encephalopathy. We studied 20 patients with influenza-associated encephalitis/encephalopathy during the last four influenza seasons. No patients had been previously inoculated with influenza vaccine. Antipyretics were used in 16 patients before the onset of encephalopathy. Although all patients were treated intensively, 5 patients died and 8 had neurologic sequelae. Patients with coagulopathy, hepatic dysfunction, and computed tomographic abnormalities had a poor prognosis. The plasma concentrations of inflammatory cytokines were variable. The neuroradiologic findings could be divided into four categories. These findings indicated that the pathogenesis of the brain damage induced by influenza infection was variable. Further investigation is necessary to determine whether insufficient influenza vaccination or the use of antipyretics is one of the reasons for these epidemics of encephalopathy in Japanese children.

Acute renal failure (ARF) is an important complication of rhabdomyolysis. However, the contributing factors to the development of ARF in children with rhabdomyolysis remain obscure. The aim of this study was to clarify the factors contributing to the development of ARF in children with rhabdomyolysis. This is a retrospective review of the clinical characteristics, laboratory data, pediatric risk of mortality (PRISM) scores, the occurrence of systemic inflammatory response syndrome (SIRS) criteria, and the number of dysfunctional organs in 18 children with rhabdomyolysis seen in our hospital between 1991 and 2000. The patients were divided into an ARF group (n=9) and a non-ARF group (n=9). All patients with ARF had more than two dysfunctional organs. The incidence of dehydration, serum concentrations of myoglobin, creatinine kinase, aspartate aminotransferase, and lactate dehydrogenase, PRISM scores, and the numbers of SIRS criteria and dysfunctional organs were higher in the ARF group than the non-ARF group. The blood pH and base excess, and urinary pH were lower in the ARF group than in the non-ARF group. These results suggest that ARF is more likely to develop in the presence of dehydration, metabolic acidosis, or severe muscle damage, or with multiple organ failure in children with acute rhabdomyolysis.

Acute necrotizing encephalopathy is a novel disease entity, proposed by Mizuguchi et al in 1995, that shows a characteristic selective and symmetric involvement of the thalamus, brain stem, and cerebellum. It usually leaves sequelae. The etiology of acute necrotizing encephalopathy is unknown. We describe here six patients aged 6 months to 5 years (four boys and two girls). Four cases were typical, and the patients' cranial computed tomographic scans and magnetic resonance imaging showed irreversible symmetric involvement of the thalamus, brain stem, and cerebellum. Three of the patients died, and one was left with severe sequelae. In the other two patients, who had selective reversible thalamic involvement, the disease was mild; one also showed transient unilateral thalamic involvement. These patients recovered completely. We consider the illness in these two patients to fit the criteria of the mild form of acute necrotizing encephalopathy. We believe that acute necrotizing encephalopathy has some clinical diversity, as is seen in other neurologic disorders, and that a mild form could exist.

Although renal Fanconi syndrome resulting from valproate (VPA) has occasionally been reported, the detailed clinical characteristics of this disease remain unclear. To clarify the clinical features of patients with VPA-induced Fanconi syndrome, we analyzed the clinical and laboratory data of seven affected patients. All patients were children, were severely disabled and required tube feeding. Five patients required treatment with multiple anticonvulsant agents. Hypophosphatemia and hypouricemia were found in all patients. Mild proteinuria, increased excretion of urinary beta2-microglobulin (beta2MG) and generalized hyperaminoaciduria were present in all patients. The renal biopsy of one patient exhibited tubulointerstitial nephritis without any structural abnormalities of the mitochondria in proximal renal tubular cells. All patients recovered from the Fanconi syndrome after the cessation of VPA therapy without any long-term renal sequellae. These results indicate that young age and being severely disabled with tube feeding and anticonvulsant polytherapy are contributory factors to the development of VPA-induced Fanconi syndrome. Serum phosphate and uric acid concentrations and urinary beta2MG levels in addition to serum electrolytes and urinalysis should be examined regularly in patients receiving VPA therapy, especially in those with the contributory factors outlined above. Patients with Fanconi syndrome caused by VPA have a favorable renal outcome.

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