We have previously reported that Sairei-to (TJ-114), a Japanese herbal medicine, prevented the production of endothelin-l in anti-GBM nephritic rats, and that Alismatis Rhizoma(Takusha in Japanese), one of the twelve herbs composing TJ-114, might be responsible for the action. In order to further clarify the antinephritic components of TJ-114, we investigated the effects of Takusha extracts on various parameters, including endothelin-1 production by glomeruli in vitro and in vivo using anti-GBM nephritic rats. McOH-100% McOH and McOH-50% McOH fractions (31.3μg/ml or higher) strongly inhibited an increase in endothelin-1 concentration in culture medium when they were added to a culture of glomerular cells derived from nephritic rats. In addition, oral administration of the MeOH-100% McOH fraction (30 mg/kg) ameliorated the proteinuria, increase in systolic blood pressure and changes in histopathological parameters in nephritic rats. Oral administration of the McOH-100% MeOH fraction inhibited increase in endothelin-1 expression in the glomeruli of nephritic rats and in endothelin-1 production by a culture of glomerular cells derived from the nephritic rats. Alisols A and B, the main constituents of the McOH-100% McOH fraction, inhibited in vitro endothelin-1 production by glomerular cells derived from the nephritic rats. Oral administration of alisol B (30 mg/kg) prevented the endothelin-1 expression by glomeruli and the increase in endothelin-1 production by cultured nephritic glomerular cells. Oral administration of alisol B also ameliorated the proteinuria, the increase in systolic blood pressure and the changes in histopathological parameters in the nephritic rats. These results indicate that the antinephritic action of TJ-114, resulting from the inhibition of endothelin-1 production, may be attributed to the alisols in Takusha.

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The association of Intracranial aneurysm with ADPKD is well-known, and patients with ADPKD are at increased risk of subarachnoid hemorrhage from rupture of Intracranial aneurysms. We prospectively performed three-dimensional time-of-flight magnetic resonance angiography (MRA) in 30 nonselective adult patients with ADPKD. Sixteen were women and 14 were men with a mean age of 51 yr (range 24 to 79 yr) . The diagnosis of ADPKD was made on the basis of abdominal ultrasound or computed tomographic studies. Three patients were on maintenance hemodialysis, 8 patients were non-dialysed patients with chronic renal failure (serum creatinine≥ 2 mg/dl) and 25 patients had hypertension (BP≥ 140/90 mmHg). None of these patients have a previous diagnosis of Intracranial aneurysm. Unruptured intracranial aneurysms were suspected in 5 patients by MRA, and 8 aneurysms were confirmed in 4 (13.3%) of 30 patients by conventional arteriography. These aneurysms were 3-l0 mm in diameter and 3 aneurysms (34 mm in diameter) were newly detected by cerebral arteriography. After informed consent was obtained, neck clipping of the intracranial aneurysms were performed successfully in all the patients. These results suggest that the prevalence of intracranial aneurysm is about 13% in ADPKD, and that MRA is useful in screening for occult intracranial aneurysms in patients with ADPKD.

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A 68-year-old male patient with chronic active hepatitis C was treated with interferon-α (IFN-α) for a period of 5 months. The patient responded well to the IFN therapy showing substantial improvement in liver function and disappearance of HCV-RNA. However, one year after the treatment he was found to have developed proteinuria and showed a reduction in Ccr. Renal biopsy findings were as follows ; Light microscopy showed diffuse expansion of mesangial cells with a focal/local increase in cellularity accommpanied by capillary loop thickening. Splitting of the basement membrane was also present. An immunofluorescent study showed that IgA was localized predominantly in the peripheral capillary wall. Electron microscopy showed that there was mesangial cell interposition between the peripheral capillary wall and endothelial cells. Furthermore, endothelial cells were expanded and numerous platelets were seen in the capillary lumen. These findings were compatible with focal MPGN accompanied by activation of endothelial cells. These histological data suggest two clinical disease entities : late-onset renal damage induced by IFN-α alone, and HCV-induced renal damage possibly modified by the direct effect of IFN-α on the endothelium. The present case suggests that IFN therapy for HCV may produce a particular type of renal damage, under the influence of either IFN or HCV infection, and/or both.

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We report here a case of severe membranoproliferative glomerulonephritis with a singular high titer of anticardiolipin antibody (aCL) . A 19-year-old Japanese female was admitted to after complaining of general edema for 5 months. She had no past history of thrombosis, thrombocytopenia, or spontaneous abortion. Laboratory findings revealed that she had nephrotic syndrome and moderate renal dysfunction. Immunological test showed a high titer of aCL with a high-normal limit of antinuclear antibody, negativity for anti-α₂ glycoprotein I antibody and negativity for anti-DNA antibody. In the renal biopsy tissue, most glomeruli showed global sclerosis and the remaining glomeruli revealed membranoproliferative change with crescent formation. Steroid therapy with warfarin and dipyridamole was effective and her renal function improved gradually. This case lacked the typical symptoms of primary antiphospholipid syndrome and did not satisfy the criteria of SLE. In spite of these findings, the singular high titer of aCL with membranoproliferative glomerulonephritis characterized this case.

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