Isao Kumagai

Mesangial Matrices Act as Mesangial Channels to the Juxtaglomerular Zone

The mesangium is centrally located in the glomerulus and plays an important role in the microcirculation within the glomerulus. In order to reveal the role of the mesangial matrix in the microcirculation, the movement of native anionic ferritin into the juxtaglomerular region was tracked following the intravenous injection of ferritin into rats. The three-dimensional ultrastructures of the mesangial matrix and juxtaglomerular apparatus were studied by conventional scanning and high-resolution scanning electron microscopy after removal of the cellular components. Many ferritin particles were observed from the glomerular capillary to the mesangial matrix, in the mesangial matrix of the juxtaglomerular apparatus and in the tubular lumen of the macula densa after the injection of ferritin. Secretion of macromolecules from the distal tubules seems to be one of the exits from the juxtaglomerular zone. The mesangial matrix was continuous from the vascular pole to the periphery like a branching tree. The intraglomerular mesangial matrix was continuous to the extraglomerular mesangial matrix in the juxtaglomerular region. The mesangial matrix appeared to consist of a polygonal meshwork structure of thin fibrils and pores with high-resolution scanning electron microscopy. The thinnest fiber was approximately 6-nm wide, and the pore size was averaged 20 nm in diameter. We were able to demonstrate the meshwork structure of the mesangial matrix, thus giving the morphological basis of the mesangial matrix to serve as mesangial pathway from the intraglomerular to the extraglomerular mesangial matrix.

Increased concentrations of the basement membrane component type IV collagen in sera and urine of diabetics

We measured serum and urinary concentrations of type IV collagen by radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) in diabetics. Serum and urinary concentrations of type IV collagen measured by RIA and ELISA were increased compared to those of control subjects. In diabetics with macroproteinuria or with renal insufficiency, serum and urinary concentrations of type IV collagen were higher than in diabetics without nephropathy or with early renal damage as determined by the presence of microproteinuria. These results suggest that serum and urinary concentrations of type IV collagen are increased in patients with advanced diabetic nephropathy. These increases may indicate that alteration of basement membrane metabolism has occurred in diabetics.

Effect of proteinase inhibitor camostat mesilate on nephrotic syndrome with diabetic nephropathy.

The effect of serine protease inhibitor Camostat Mesilate on nephrotic syndrome with diabetic nephropathy was evaluated. Eight patients with nephrotic syndrome associated with diabetic nephropathy were orally administered 600 mg of Camostat Mesilate per day. Three patients showed a reduction of urinary protein excretion promptly at 4 weeks. Serum protein and degree of edema improved significantly at 4 weeks. Camostat Mesilate had no effect on renal function assessed by creatinine clearance. During the observation period there were no significant changes in blood pressure, level of blood sugar, or HbA1c. Camostat Mesilate would be beneficial for the treatment of diabetic nephropathy.

Effect of methylprednisolone pulse therapy in patients with lupus nephritis assessed by WHO morphologic classification

To determine indications for treatment with high-dose intravenous methylprednisolone pulse therapy in lupus nephritis, we retrospectively assessed the response to pulse therapy over oral prednisolone administration in 120 biopsy proven lupus nephritis patients according to WHO morphologic classification. In the pulse group, 1 g of methylprednisolone was administered on three consecutive days and oral steroid therapy (40-30 mg) was started. In many occasions in treating class III and IV-b, repeated pulse therapy was performed. In control oral prednisolone group, middle-dose steroid therapy (50-30 mg) was started. In patients with minor glomerular abnormalities and mesangial lupus nephritis, rapid improvement of serological activities was observed in pulse group assessed by serum complement level, anti-DNA antibodies, and anti-nuclear antibodies. In patients with focal lupus nephritis, rapid rise in serum complement level and fall in proteinuria was observed in the pulse group. In patients with diffuse proliferative lupus nephritis with active necrotizing lesions, faster rise in serum complement level and proteinuria were observed in the pulse group. In patients with membranous lupus nephritis there was no significant difference between two groups. In comparison with the effect of pulse therapy among each morphologic class, the rise of serum complement level was slowest in class IV-b. Both group of IV-b and V manifested nephrotic syndrome and by pulse therapy the decrease in urinary protein was faster and more significant in class IV-b compared with class V. No significant adverse effect of methylprednisolone was observed during about 150 times of pulse therapy. Bacterial, viral infections such as herpes zoster and fungal infections were observed in pulse group as often as control group.

Escape of red blood cells through gaps in glomerular basement membrane in a patient with mixed connective tissue disease

Hematuria in patients with glomerulonephritis seems to result from the passage of red blood cells through anatomical gaps in the glomerular basement membrane. However, such morphological evidence has rarely been demonstrated. A patient with mixed connective tissue disease associated with membranous glomerulonephritis is described in whom the renal biopsy specimen showed an escape of red blood cells through a gap in the basement membrane. These findings support the morphological basis of hematuria in glomerulonephritis.

A Case of Nephrotic Syndrome and Renal Dysfunction in a Pregnant Woman with Diabetes Mellitus

A 29‐year‐old diabetic woman who developed severe anaemia, nephrotic syndrome, and hypertension before the 28th week of gestation, had residual evidence of toxaemia and renal dysfunction more than 1 month following delivery. The histopathological findings of renal biopsy specimens were considered most consistent with toxaemia of pregnancy complicated by diabetic glomerulosclerosis. We consider that rapid acceleration of renal dysfunction may have been induced by: (1) poor control of diabetes before pregnancy; (2) glomerular hyperfiltration of the remnant nephrons throughout pregnancy; (3) hypercoagulopathy associated with pregnancy; (4) appearance of hypertension following these three conditions.

Study on changes in plasma vitronectin levels during hemodialysis.

血漿vetronectin (VN) 値は, 血液透析患者では低値を示すが, 透析歴が長くなるほど, より低値を示すことが知られている. そこで, 今回我々は, 同一患者に対し, regenerated cellulose (RC膜), cellulose triacetate膜 (CTA膜), polysulfone膜 (PS膜) の3種類の透析膜を順次変えて血液透析を施行し, その際の血漿VN値の変動を測定することにより, これらの透析膜で血漿VN値の変動に有意な変化があるか否かを検討した. また, 抗凝固剤としてのheparinの影響の有無を検討するため, 抗凝固剤として, heparinを使用した時とnafamostat mesilate (NM) を使用した時の, 血漿VN値の変動を比較検討した.その結果, すべての膜において, 透析開始前の血漿VN値は, 正常値より低値を示した. 血漿VN値の変動では, RC膜のみ有意な変化を認め, 透析開始後15分の血漿VN値が, 開始前に比べ有意に低値を示したが, CTA膜, PS膜には, 有意な変動を認めなかった. 従って, 使用している透析膜の種類により補体活性化の程度が異なり, VNの消費の程度が異なってくることが示唆された. また, 抗凝固剤による検討では, すべての膜において, heparin使用時とNM使用時とでは, 血漿VN値の変動に関し有意差を認めなかったため, VNがheparinと結合することによりVNが消費されるという説を支持する結果は得られなかった.

Effect of a soybean fat emulsion on refractory pruritus cutanea in patients on chronic hemodialysis therapy.

慢性透析患者の合併症の一つである皮膚掻痒症は, いまだに原因は十分に解明されておらず, そのため治療法も確立していない.そこで, 今回我々は, 脂肪乳剤の投与条件を設定し, その条件を満たす難治性の皮膚掻痒症を有する慢性血液透析患者7名に対し, 脂肪乳剤の投与を行った. その結果, 皮膚乾燥に対しても, 掻痒感に対しても, 同じ5名 (71.4%) の有効性を認めた. また脂肪乳剤投与前後における検査値で有意差を認めた検査項目はなく, 副作用は認めなかった. しかし投与終了4週後には, 脂肪乳剤の有効性を認めた5名のうち4名が増悪し, 再投与により, 再び改善を認めた.このように, 適応を十分に考慮すれば, 脂肪乳剤が慢性透析患者の難治性皮膚掻痒症に対して有効かつ安全な薬剤であることが確認された. 今後, この脂肪乳剤の皮膚掻痒に対する有効性の機序が明らかにされれば, より有効で安全な薬剤の開発や, あるいは新たな透析方法の開発が期待できるものと考えられる.

Myeloma kidney associated with acute renal failure after pneumonia.

骨髄腫腎に肺炎を契機に発症した急性腎不全の1例を経験し, 治療により血液透析より離脱し得たので報告する.症例は74歳, 男性. 肺炎に続発して無尿となり補液や利尿剤などの投与を受けた. しかし急性腎不全がさらに進行したため血液透析を開始した. 骨髄穿刺, 血清および尿中免疫電気泳動などで多発性骨髄腫と診断した. 腎機能の回復が遅れていたため腎生検を施行し骨髄腫腎と診断した. そこで化学療法 (MP療法) を開始したところ, 腎機能が次第に回復し血液透析より離脱し得た.多発性骨髄腫の急性腎不全合併例には, 脱水, 感染症, その治療に対する抗生剤, 高カルシウム血症, 造影剤などの誘因に対する処置や, 血液透析や血漿交換などの適切な血液浄化法の選択, および多発性骨髄腫に対する化学療法など, 積極的な治療が重要であると考えられた.

Effect of Proteinase Inhibitor Camostat Mesilate on Nephrotic Syndrome

The effect of serine protease inhibitor Camostat Mesilate on nephrotic syndrome with diabetic nephropathy was evaluated. Eight patients with nephrotic syndrome associated with diabetic nephropathy were orally administered 600 mg of Camostat Mesilate per day. Three patients showed a reduction of urinary protein excretion promptly at 4 weeks. Serum protein and degree of edema improved significantly at 4 weeks. Camostat Mesilate had no effect on renal function assessed by creatinine clearance. During the observation period there were no significant changes in blood pressure, level of blood sugar, or HbA1c. Camostat Mesilate would be beneficial for the treatment of diabetic nephropathy.