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Background MLT-550N is a device to measure the body fluid volume based on bioimpedance spectroscopy. When extracellular water (ECW) or total body water (TBW) is measured with MLT-550N before and after hemodialysis, the change in ECW (ΔECW) or TBW (ΔTBW) is markedly larger than the change in body weight (ΔW). Good agreements between ΔECW and ΔTBW calculated by Moissl equations with ΔW were reported. The aim of this study was to develop novel equations to calculate the body fluid volume by modifying Moissl equations. Methods A total of 466 measurements of 351 hemodialysis patients were used to develop the novel equations. The equations were based on the agreement between ΔECW and ΔW as a guide. The volume of intracellular water was postulated to be constant during hemodialysis. For evaluation of the equations, 5485 measurements of 627 patients were used. Agreements between values of two groups were assessed with Lin’s concordance correlation coefficients. The normal edema ratio (ER = ECW/TBW) corrected with the fat ratio (fcER) according to the parameters of normally hydrated lean and adipose tissues was used as the reference for normal hydration. The fluid status at dry weight was considered to be close to normal. The absolute values of the deviated ratio of actual ER (aER) from fcER (dER = (aER−fcER)/fcER) were compared. In this study, 1 L of body water corresponded to 1.02 kg of body fluid according to a previous report. Results The concordance correlations between ΔW and 1.02∙ΔECW or 1.02∙ΔTBW with the novel equations were higher than with the MLT method or Moissl equations (0.896, 0.596 vs. 0.411, 0.375 or 0.813, 0.411, respectively). The median value of dER with the novel equations was the lowest (0.062) compared with those of the MLT method and Moissl equations (0.164 and 0.144) (p

シャントなどのバスキュラーアクセスが確立していない患者に対して血液浄化療法が必要になった場合，ダブルルーメンカテーテルを中心静脈に留置して治療を開始することが一般的であるが，この方法は血流感染症・血栓形成など重篤な合併症のリスクを伴う．われわれは各種血液浄化法が必要となった症例に対し，バスキュラーアクセスが確立されるか血液浄化療法を離脱するかいずれの状況まで血液浄化のたびに超音波ガイド下で大腿静脈に透析針を挿入することで，ダブルルーメンカテーテルを使用することなく血液浄化を施行した．2008年6月から2011年8月まで当院で超音波ガイド下大腿静脈反復穿刺法にて血液浄化法を施行した16例を対象とした．基礎疾患は慢性腎不全が9例（糖尿病性腎症5例，腎硬化症2例，慢性糸球体腎炎1例，原因不明1例），膠原病が3例，ネフローゼ症候群が2例（微小変化群1例，原因不明1例），急性腎不全とM蛋白血症に伴う多発ニューロパチーが各1例であった．ステロイド・免疫抑制剤を投与中の患者は16例中6例であった．血液浄化法の内訳は血液透析が11例，二重濾過血漿交換・単純血漿交換併用が1例，二重濾過血漿交換単独が2例，ECUMが1例とLDL吸着が各1例であった．16ゲージの透析用長針を用い，穿刺に際して穿刺針に生じる音響陰影に着目し，積極的に超音波プローブを走査することで針先位置を特定した．大腿静脈は脱血側とし，返血側は四肢の皮静脈に通常の方法で穿刺した．16例に対し総計156回（1～48回，平均9.8回），本法による血液浄化を施行したが，新たな血流感染症や血腫形成は認めなかった．大腿動脈には分枝が多く解剖学的知識や触診に基づいた大腿静脈反復穿刺法では一定の確率で動脈性出血を起こしうるが，本法により安全・確実な血液浄化療法が施行可能であった．ダブルルーメンカテーテルの留置を避けたい場合に本法は一時的バスキュラーアクセスとして有用と思われた．

動脈を表在化した血液透析患者の返血用皮静脈が荒廃して穿刺困難になると，グラフトへ変更することが一般的であるが，その後グラフト感染による敗血症が疑われるような場合は，ダブルルーメンカテーテルの留置は感染治療において不利と考えられる．グラフト感染による敗血症を契機にバスキュラーアクセス不全に陥った2症例に対し，リアルタイムエコーガイド下に上腕の皮下深い位置にあるbrachial vein（上腕静脈）を反復穿刺して返血路とすることで，感染が沈静化するまでダブルルーメンカテーテル留置を避けることが可能であった．穿刺は当科の医師3名のいずれかが行い，リニアプローブ付きポータブル超音波装置（iLook25，ソノサイト社）を用いた．その際，(1) 術者はあらかじめ当科で自作したシミュレータで訓練を行った上で，(2) 穿刺前に上腕静脈の走行と上腕動脈・神経との位置関係をエコーにより十分観察し，(3) 穿刺時に血管短軸横断像を描出し，血管穿刺針とエコービームを直交させ，針の輝度を向上させることで皮下における正確な針先位置を同定し，(4) 血管内に針先が到達後もプローブと穿刺針を交互に僅かに進める操作を繰り返し，血管壁損傷を避けつつ，透析針外筒先端が血管内に十分入るように留置した．その結果，2症例合わせて計51回上腕静脈穿刺を行い，透析針外筒留置成功率100％，動脈誤穿刺0％，神経損傷0％であり，重篤な合併症を認めなかった．結論：返血用皮静脈が荒廃した上腕動脈表在化患者等でも上腕静脈は温存されていることが多く，新たなバスキュラーアクセス確立までの間の一時的アクセスとして，エコーガイド下で反復穿刺し返血路として使用することが可能である．特に，すでに感染症を合併している場合にはダブルルーメンカテーテルを留置するよりも感染治療上有利と考える．

Direct inhibitory effects of simvastatin on matrix accumulation in cultured murine mesangial cells Background 3-Hydroxy-3-methylglutarylcoenzymeA(HMG-CoA) reductase inhibitors have been demonstrated to suppress glomerular injuries in various renal diseases. These agents inhibit in vitro proliferation of several cell types, including mesangial cells. This effect indicates the ability to ameliorate mesangioproliferative lesions, independent of the improvement of hypercholesterolemia. On the other hand, it is not clear whether HMG-CoA reductase inhibitors directly regulate extracellular matrix (ECM) accumulation from mesangial cells. Methods In this study, to examine the in vitro effects of simvastatin, an HMG-CoA reductase inhibitor, on mRNA expressions of matrix proteins, growth factors, and matrix turnover proteins, we incubated cultured murine mesangial cells stimulated by fetal calf serum (FCS) with or without simvastatin for 24 hours, and Northern analysis was performed. Results Simvastatin showed a slightly suppressive effect on mRNA expression of type IV collagen and fibronectin and a slightly up-regulative effect on that of type I collagen, whereas mRNA expression of type III collagen was markedly up-regulated. mRNA expression of platelet-derived growth factor (PDGF)-B chain and PDGF receptor β-subunit was suppressed, whereas that of transforming growth factor-β (TGF-β) was not affected by simvastatin. Concerning matrix turnover proteins, simvastatin markedly reduced mRNA expression of plasminogen activator inhibitor-1 (PAI-1) without affecting the expression of tissue-type plasminogen activator (tPA). Conclusion These results suggest type-specific modulation of matrix protein production independent of TGF-β and the suppressive effects of autocrine PDGF by administration of HMG-CoA reductase inhibitors in mesangial cells. Moreover, the beneficial effects of these agents on matrix protein accumulation may be through promoting ECM degradation derived from PAI-1 suppression.

Up-regulation of glomerular extracellular matrix and transforming growth factor-βbgr; expression in RF/J mice. Background RF/J mice were first reported as a murine model of spontaneous glomerulosclerosis by Gude and Lupton in 1960, but the precise histologic characteristics and immunopathological background of this mouse have not been investigated further. Methods Measurements of serum levels of immunoglobulins, anti-single strand DNA (anti-ss-DNA) antibody, complement (C 3 ), and circulating immune complex (IC) were performed. Analyses of glomerular histological and immunopathological lesions in association with the detection of mRNA expression of collagen IV, TGF-βbgr;, matrix protein turnover related enzymes, matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2) and platelet-derived growth factor (PDGF) were also performed in young (10-week-old) and elderly (60-week-old) RF/J mice with age-matched BALB/C mice as the controls. Results High levels of serum IgA and IgG from as early as 20 weeks of age were noted in the RF/J mice. Serum anti-ss-DNA antibody of aged RF/J mice increased up to 23% of that of aged MRL- lpr/lpr mice, and serum C 3 concentration significantly decreased with age, reaching lower levels than that of BALB/c mice. IgA-IC levels were significantly high compared to BALB/C mice both in the early and late stages of life, whereas IgG-IC levels were high only in mice younger than 20 weeks. Semiquantitative and quantitative analyzes of renal histopathological findings revealed significantly marked and age-related mesangial matrix expansion in RF/J mice, with increasing frequency of global glomerular sclerosis and tubulointerstitial damage. On the other hand, although precise measurements of glomerular cell numbers also showed an apparent augmentation in both young and old RF/J mice compared to BALB/C mice, glomerular cellularity decreased with age in RF/J mice. Immunohistochemical study revealed massive immunoglobulin deposition from a young age in association with significantly higher accumulation of matrix proteins, such as types I and IV collagen and laminin from the early stage of life. In addition, in these glomeruli, transforming growth factor-βbgr;1 (TGF-βbgr;1) was highly expressed both in young and old mice. The mRNA expression of MMP-2 was up-regulated only in the early stage of life. Although PDGF mRNA of RF/J mice was significantly up-regulated in the early stage of life, the differences between the mice disappeared in the late stage of life. Conclusions These findings suggest that in RF/J mice, an immunopathological background inducing high serum immunoglobulin and IC levels from the early stage of life is closely related to mesangioproliferative glomerular lesions mediated by PDGF, and that development of massive extracellular matrix accumulation in glomeruli was induced by up-regulated expression of TGF-βbgr; with inappropriate regulation of protein turnover-related enzyme production.

Mesangiolytic glomerulopathy in severe congestive heart failure. To study the glomerular morphological abnormalities in congestive heart failure (CHF), we analyzed 27 autopsy cases without other causes of renal disease. Their mean age was 59 years, and they showed mild prerenal azotemia. They had generally been treated with digitalis and diuretics, and a few of them with captopril or nifedipine. The abnormal glomerular findings of enlargement, hyperemia, and mesangial thickening were observed at high frequencies (61%, 64%, and 57%, respectively). They characteristically showed mesangiolysis (ML) by the findings of microaneurysms (81%) and mesangial degeneration (70%) such as loose reticular matrix and poor matrix area. In addition, glomerular infiltration of mononuclear leukocytes including macrophages was noted in 70% of the cases. Glomerular enlargement was not correlated with the grade of hyperemia, but it was correlated with the grade of ML index of % glomeruli with microaneurysms (F = 7.22, p < 0.004). There was an inverse relationship between the grades of mesangial thickening and of the ML index (P < 0.005). The number of glomerular leukocytes was positively correlated with mean glomerular size (P < 0.002) and with the ML index (P < 0.03). Notably, the glomerular macrophage-positive cases showed a prominently higher mean ML index than the negative cases (P < 0.005). There was an inverse correlation between the mean glomerular size and the partial oxygen pressure in arterial blood (PaO2; P < 0.01), and a positive correlation between the mean glomerular size and hematocrit (Hct) levels (P < 0.02). The cases positive for mesangiolytic mesangial degeneration showed significantly lower PaO2 values than the cases negative for this lesion (P < 0.04). In the analysis of the various causes of CHF, the patients with congenital cardiac anomalies showed mean levels of the lowest PaO2 (P < 0.02) and the highest Hct (P < 0.03) and histologically the largest mean glomerular size (P < 0.04). There was no difference in the ML index and the glomerular leukocyte number among the subgroups classified by the causes. These results indicate that ML associated with glomerular enlargement is the major glomerular abnormality characteristic in patients with severe CHF and suggest that glomerular infiltration of leukocytes, especially of macrophages, should play an important role in the progression of both ML and glomerulomegaly. The contributions of persistent hypoxia and up-regulated angiotensin II as the causative factors of these glomerular abnormalities in congestive heart failure are discussed.

巣状糸球体硬化症 (FGS) による7例のネフローゼ症候群 (男性3例, 女性4例, 年齢16-56歳, 平均30.3歳) に対してLDL吸着療法を施行しその効果を検討した. LDL吸着はdextransulfate cellulose column (Liposorba LA-15) を使用し1回の血漿処理量は4,000mlとした. LDL吸着前のネフローゼ持続期間は1.5か月から26か月, 吸着療法の施行回数は2から13回であった. 7例中4例が不完全寛解I型となり, 2例はネフローゼ状態のままで, 1例では末期的腎不全に進行し透析導入となった. 寛解した4例では, LDL吸着療法前のネフローゼ持続期間が1.5-4 (平均2.4) か月だったのに対し, 無効例では3-26 (平均13) か月とより長期であった. 治療前の血清総コレステロール (TC) 値, 1回の吸着療法でのTCの平均低下率には, 寛解例, 無効例で差を認めなかったが, 吸着療法施行中のTCのtime average concentration (TAC) は寛解例では173-269 (平均234.5) mg/dl, 無効例では280-302 (平均292.7) mg/dlと, 前者でより低い値に維持されており, またより高頻度で吸着療法が施行されていた. 腎組織のapoprotein B (apo B) の蛍光抗体所見では, 改善した3例中2例で治療後にapo Bのメサンギウムへの分布低下が見られたが, 一方TC維持レベルが高値であり腎不全へと移行した例では治療後にむしろ増強傾向にあった. 薬剤療法が無効のFGSによるネフローゼ症候群では90%が腎不全に至るとの報告があるが, 今回の検討では薬剤が無効であった5例中2例が不完全寛解I型以上の改善を示し, 1例が腎不全に陥ったのみで, LDL吸着療法の有効性が示唆された.

術後の肝不全症例に対して血漿吸着療法を行ってきたが, その治療効果を高めるため, 非被覆性チャコール (N350) とstyrenedivinylbenzene (BR 350) を使用した血漿吸着療法を血漿交換療法に併用する方法を考え, 灌流実験ならびに臨床応用してその結果を検討した.灌流実験では, 以前に行った血漿交換時に得られた高ビリルビン血漿を用いて, 3時間吸着カラムを灌流した. 総ビリルビンは, BR350およびN350の単独使用では40%以上の残存率を, BR350とN350の直列併用では21%にまで減少していた. アミノ酸についてはBR350単独では, 総・分枝鎖・芳香族アミノ酸は87%, 93%, 70%の残存率を示したが, N350ならびにBR350とN350の直列併用では, 各々50%, 40%, 7%であり良好な吸着能が認められた. 臨床症例においては, 総ビリルビンは57±6%に, 芳香族アミノ酸は84±7%に減少した. 症例の長期的な予後は決して良好とはいえないものの, 臨床症状の改善やデータの改善がみられた.この血漿吸着療法は, 肝不全症例, 特に肝性昏睡や高ビリルビン血症を有する症例に対して, 従来の血漿交換療法とほぼ同等のビリルビン低下効果と臨床症状の改善を認め, 高価でかつ入手困難な新鮮凍結血漿 (FFP) の使用量を1/4に低下させ得たことより評価し得る治療法と考えられる.

Enhanced production of glomerular extracellular matrix in a new mouse strain of high serum IgA ddY mice. To investigate the relationship between high serum levels of IgA and glomerular lesions, selective mating was performed in high serum IgA ddY mice, a murine modelof spontaneously developing mesangioproliferative glomerulonephritis mimicking human IgA nephropathy. The selection and mating of high IgA ddY mice were accomplished when the mice were three to fourmonths old. In the 12th generation of high IgA ddY (HIGA) mice, significantly higher levels of serum IgA from 10 age weeks to 60 weeks (P < 0.0002 to 0.0001) were observed in comparison with BALB/c mice. Relatively high proteinuria was observed at 40 weeks of age, although hematuria was consistently negative. Microscopic observations of renal tissue disclosed a marked glomerular mesangial matrix increase and a reduction of cell proliferation with age by both semiquantitative and morphometric analyses with moderate tubulointerstitial damage. These mesangial matrices were stained markedly by antisera for collagen type IV and by fibronectin, but not by collagen type I. Localization of TGF-β protein was also detected in the mesangium of the HIGA mice. The positive mesangial IgA deposition was maintained consistently by this mating procedure and became more marked with age. Size analysis of IgA from ten pooled HIGA mice aged 50 to 60 weeks revealed dominant polymeric IgA insera and dimeric IgA in glomerular eluates. Clonal analysis of serum IgA disclosed heterogeneous spectrotypes in a wide pH range (4.5 to 6.5), in contrast to very limited spectrotypes in the acidic pH range (4.5 to 5.2) of IgA in the glomerular eluates from these mice. The analyses of retroviral gp70 antigen involvement in the HIGA mice disclosed a significant increase of serum levels of gp70 anti-gp70 immune complexes with age, with no relationship to the severity of glomerular gp70 deposition. Northern blot analysis of renal tissue revealed markedly high mRNA expression of collagen type I, IV, fibronectin and TGF-β even in 10-week-old HIGA mice in comparison with BALB/c mice. The expression became more significant in 60-week-old animals. The genetic background required to induce the expansion of IgA-producing B-cell clones is suggested to be closely related to the increased gene expressionof TGF-β, which induces enhanced glomerular extracellular matrix (especially fibronectin) accumulation in HIGA mice, being possibly mediated by the mesangial deposition of dimeric and highly acidic IgA. This newly established strain may provide a model for investigating the relationship between progressive glomerular sclerotic lesions and the induction of pathogenic IgA in human IgA nephropathy.