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We developed a new optical device (Nikkiso) to assess changes through blood volume monitoring (BVM) during hemodialysis and were able to determine the ideal levels in which changes in blood volume percentage (BV%) occur among hemodialysis patients in one hemodialysis center. We evaluated both the reliability of BVM and these ideal levels in a multicenter group. The purpose of this manuscript is to develop a navigating system to set dry weight in a variety of situations as the final goal. First, based on the obtained BVM (BV%(BVM) ) measurements, the relationships between BV% and hematocrit (BV%(HT) ) and between BV% and CRIT-LINE (BV%(CLM) ; Hema Metrics, Kaysville, UT, USA) were then evaluated. In 30 hemodialysis patients, there was a close correlation between both BV%(BVM) vs. BV%(HT) and BV%(BVM) vs. BV%(CLM) (n=30, r=0.967, P

We herein report a case of ureter rupture with severe oliguric acute renal injury due to benign prostatic hypertrophy. After insertion of an indwelling urinary catheter, the patient’s urine output immediately increased. His symptoms and renal function also rapidly improved to the normal range without a surgical operation. Clinicians should note this complication in patients with oliguria.

われわれは，透析患者の除水による循環血液量の変化をモニターする機器（Blood Volume Monitoring system：BVM）を日機装社（静岡）と共同開発し，多施設共同研究において臨床的にドライウエイト（DW）が適正と判断された患者の循環血液量の変化（BV％）の予想範囲を設定し，すでに報告した（Ther. Apher. Dial. in press）．本論文では，その予想範囲が適正な除水量設定に有用か否かを検討した．維持透析を行っている9施設の144名を対象とし，採血日を含む3回の透析日に，BVM搭載装置を用いて透析を行った．DWが適正と判断された患者のBV％予想範囲は，上限ライン：BV％/BW％後＝－0.437t－0.005 下限ライン：BV％/BW％後＝－0.245ln(t)－0.645t－0.810．BV％は循環血液量変化率，BW％後は透析による除水量の前体重に対する比率，tは透析時間（h）．今回の検討では，DW適正の可否を問わずに144例を抽出し，430データを集積した．プロトコール違反の94データを除外した336データを解析対象症例とした．各施設の判断によりDW適正と判断された230データで，BVMでも適正と判断された適正合致率は167データ（72.6％）であった．臨床的にDWを上げる必要があると判断された45データで，BVMでもDWを上げる必要があると判断されたのは10データ，逆に臨床的にDWを下げる必要があると判断された61データで，BVMでも下げる必要があると判断されたのは37データであった．その結果，BVMによる判定と臨床的判定の適合率は63.7％であった．不適合の原因としては，バスキュラーアクセスの再循環率（VARR），体位変換，体重増加量が1.0kg以下などであった．PWI（Plasma water index）による判定との適正合致率は71.6％で，適合率は58.0％であった．hANPによる判定との適正合致率は68.8％で，適合率は48.7％であった．循環血液量のモニターは，透析患者の除水設定管理の一助になり，われわれが設定したBV％予想範囲は臨床的にも妥当性が高いと考えられた．

Peritoneal fibrosis (PF) is an intractable complication leading to peritoneal membrane failure in peritoneal dialysis (PD). The aim of this study was to identify microRNAs (miRNAs) involved in PF. Peritoneal tissue from a PF rat model was screened for miRNA expression using microarray analysis. The expression levels of differentially expressed miRNAs were evaluated in serum and drained dialysate and associated with peritoneal membrane functions, as measured by the peritoneal equilibrium test in 33 PD patients. Furthermore, an miRNA inhibitor (anti-miRNA-21-5p locked nucleic acid (LNA): anti-miRNA-21-LNA) was intraperitoneally injected to PF model mice to investigate its effects on PF. The initial profiling study of PF rat peritoneal tissue identified 6 miRNAs (miRNA-142-3p, miRNA-21-5p, miRNA-221-3p, miRNA-223-3p, miRNA-34a-5p, and miRNA-327) whose expression was increased more than 2-fold and no miRNAs whose expression was decreased more than half. Among them, serum levels of miRNA-21-5p, miRNA-221-3p, and miRNA-327 and drained dialysate levels of miRNA-221-3p and miRNA-34a-5p were significantly correlated with peritoneal membrane functions in PD patients. Anti-miRNA-21-LNA significantly inhibited miRNA-21-5p expression in the PF mouse peritoneum, inhibited peritoneal fibrous thickening, and maintained peritoneal membrane functions. These results suggest that several miRNAs are involved in PF and that they may be useful as novel diagnostic biomarkers and therapeutic targets for PF.

A 78-year-old woman diagnosed with non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency had been under glucocorticoid replacement therapy since the age of 17 years. After several weeks of suffering from gastroenteritis with vomiting, she presented with disturbance of consciousness, hypotension, dehydration, and severe hyponatremia (108 mEq/L) and a markedly increased serum vasopressin concentration (45.5 pg/mL). She regained consciousness after correcting her body-fluid balance with hypertonic saline and intravenous hydrocortisone sodium therapy. Her hyponatremia was likely caused by extra-renal sodium loss and impaired water excretion induced by an increase of serum vasopressin due to volume depletion and glucocorticoid deficiency.

The following conventional calcium correction formula (Payne) is broadly applied for serum calcium estimation: corrected total calcium (TCa) (mg/dL) = TCa (mg/dL) + (4 - albumin (g/dL)); however, it is inapplicable to chronic kidney disease (CKD) patients. A total of 2503 venous samples were collected from 942 all-stage CKD patients, and levels of TCa (mg/dL), ionized calcium ([iCa(2+) ] mmol/L), phosphate (mg/dL), albumin (g/dL), and pH, and other clinical parameters were measured. We assumed corrected TCa (the gold standard) to be equal to eight times the iCa(2+) value (measured corrected TCa). Then, we performed stepwise multiple linear regression analysis by using the clinical parameters and derived a simple formula for corrected TCa approximation. The following formula was devised from multiple linear regression analysis: Approximated corrected TCa (mg/dL) = TCa + 0.25 × (4 - albumin) + 4 × (7.4 - p H) + 0.1 × (6 - phosphate) + 0.3. Receiver operating characteristic curves analysis illustrated that area under the curve of approximated corrected TCa for detection of measured corrected TCa ≥ 8.4 mg/dL and ≤ 10.4 mg/dL were 0.994 and 0.919, respectively. The intraclass correlation coefficient demonstrated superior agreement using this new formula compared to other formulas (new formula: 0.826, Payne: 0.537, Jain: 0.312, Portale: 0.582, Ferrari: 0.362). In CKD patients, TCa correction should include not only albumin but also pH and phosphate. The approximated corrected TCa from this formula demonstrates superior agreement with the measured corrected TCa in comparison to other formulas.

POEMS syndrome is a rare plasma cell disorder, characterized by polyneuropathy, organomegaly, endocrinopathy, serum monoclonal protein, and skin lesions. Although not included in the acronym, renal lesions also are characteristic of this disease and sometimes require dialysis therapy. We treated a 61-year-old woman with POEMS syndrome with high-dose melphalan therapy (HDT) supported by autologous blood stem cell transplantation (SCT), and clinical remission was achieved. A repeated renal biopsy showed the striking effectiveness of this therapy on renal lesions. Pathological features of the renal lesions, such as membranoproliferative glomerulonephritis-like lesions, microangiopathic glomerulopathy, and mesangiolytic lesions with microcapillaries, almost completely disappeared. This treatment also markedly decreased serum levels of vascular endothelial growth factor (VEGF). These findings indicate that HDT with SCT is effective, even on renal lesions in patients with POEMS syndrome, and suggest that high serum VEGF concentrations are associated closely with the development of renal lesions in patients with this type of plasma cell disorder.

Type 2 diabetic kidney disease (DKD) is the most common cause of end-stage renal failure, and the prevention of its progression has been a topic of discussion.Sixty type 2 DKD patients were retrospectively evaluated for 1 year. Factors independently affecting the annual Ccr decline were examined by multivariable linear regression analysis. Patients were further divided into 2 groups based on their degree of renal function, and between-group differences at study initiation were evaluated.Ccr values were 21.0 ± 11.8 mL/min/1.73 m(2) at study initiation, and 15.7 ± 10.9 mL/min/1.73 m(2) after 1 year of observation. The multivariable linear regression analysis indicated salt intake (standardized coefficient: -0.34, P = 0.010) and urinary protein excretion (standardized coefficient: -0.33, P = 0.011) to be factors independently affecting the annual Ccr decline. Although decliners (-9.8 ± 4.7 mL/min/1.73 m(2)/year) had a significantly higher salt intake than non-decliners (-1.1 ± 3.8 mL/min/1.73 m(2)/year) at study initiation, this difference disappeared at the end of the study as a result of intensive dietary education. In 21 decliners with an additional year of follow-up, the annual Ccr decline significantly improved from -10.1 ± 5.3 to -5.3 ± 7.4 mL/min/1.73 m(2)/year (P = 0.02).Salt intake and urinary protein excretion were associated with annual Ccr decline in type 2 DKD patients. Furthermore, dietary education covering salt intake may have positively affected the change in Ccr.

Quantifying hemodialysis (HD) treatment requires knowledge of the equilibrated concentrations of the post-HD small molecule rebounds. However, measurement of the equilibrated concentrations is only possible after resting in bed after HD for at least 30 min, and this is often impractical. Therefore, we have analyzed mathematically the time course of post-HD urea rebound, and from this, have derived a new formula for predicting its equilibrated concentration. The blood urea nitrogen (BUN) was measured at 10 time points (immediately following HD, and 0.5, 2.5, 5, 7.5, 10, 15, 20, 25, and 30 min post-HD) in 12 anuric HD patients. The absolute change in the urea rebound (DeltaeqBUN) was approximated (DeltaestBUN) using the equation: DeltaestBUN = b -[1-exp x (-c x time (min))] + a x time (min). After the good correlation between DeltaeqBUN and DeltaestBUN, we compared the value of DeltaeqBUN measured at 30 min (DeltaeqBUN(30)) with that calculated (DeltaestBUN(30)) using only four sample points (immediately following HD, and 2.5, 5 and 10 min post-HD). Based on this result, we tried to predict post-HD BUN at 30 min (estBUN(30)). This study was undertaken to determine whether estBUN(30) may be representative of the equilibrated BUN (eqBUN(30)), and to compare with Kt/V using estBUN(30) and eqBUN(30). There was a significant correlation between DeltaeqBUN and DeltaestBUN (0.97 < r < 0.99, P < 0.001). Thus, there was a significant positive linear correlation between eqBUN(30) and estBUN(30) (eqBUN(30): 25.7 +/- 2.25 mg/dL, estBUN(30): 26.3 +/- 2.31 mg/dL; r(2) = 0.99, P < 0.001). A Kt/V measurement was obtained with single pool model using BUN just after HD (Kt/V(sp)), eqBUN(30) (Kt/V(eq)), and estBUN(30) (Kt/V(est)), and with double pool model using Kt/V(sp) (Kt/V(dp)) and was compared with them. Though Kt/V(sp) was significantly higher than Kt/V(eq) (1.26 +/- 0.08 vs. 1.09 +/- 0.07, P < 0.001), there were no differences among Kt/V(eq), Kt/V(est) and Kt/V(dp) (Kt/V(est): 1.06 +/- 0.07, Kt/V(dp): 1.10 +/- 0.07) and all values were clinically acceptable. Furthermore, there was a significant positive linear correlation between Kt/V(eq) and Kt/V(est) (r(2) = 0.98, P < 0.001). In conclusion, we have devised the method to predict equilibrated BUN and calculate double pool Kt/V, which requires samples up to 10 min post-HD.

Sir,Atrial fibrillation (Af) is an important risk factor for cerebral infarction and peripheral arterial thromboembolism.1,2 Acute renal infarction (RI) induced by Af was reported to occur in only ...

Peritoneal fibrosis is a crucial complication in patients receiving peritoneal dialysis. It is a major pathological feature of peritoneal membrane failure, which leads to withdrawal of peritoneal dialysis. No specific therapy has yet been established for the treatment of peritoneal fibrosis. However, gene therapy may be a viable option, and various nano-sized carriers, including viral and non-viral vectors, have been shown to enhance the delivery and efficacy of gene therapy for peritoneal fibrosis in vivo. This review focuses on the use of nano-sized carriers in gene therapy of peritoneal fibrosis in vivo.

Background Patients undergoing hemodialysis (HD) often develop cerebral disease complications. Furthermore, cerebral regional saturation of oxygen (rSO2) was previously reported to be significantly lower in HD patients than in healthy subjects. We aimed to identify the factors affecting the cerebral rSO2 in HD patients. Methods Fifty-four HD patients (38 men and 16 women; mean age, 67.7 ± 1.2 years, HD duration, 6.5 ± 1.9 years) were recruited. Cerebral rSO2 was monitored at the forehead before HD using an INVOS 5100C (Covidien Japan, Tokyo, Japan). Results The rSO2 levels were significantly lower in HD patients compared with healthy controls (49.5 ± 1.7% vs. 68.9 ± 1.6%, p

Colloid osmotic pressure (COP) is important in calculating vascular permeability during hemodialysis (HD). However, few reports have directly measured COP in HD patients. Therefore, the currently published formulas may not be clinically optimal for predicting COP for HD patients. Here, the study aims were (i) to directly measure COP in HD patients and compare the measured and predicted COP values using four previously reported formulas, and (ii) to develop a formula for approximating COP using clinical parameters. We obtained 212 measured COP values using an osmometer; the average value was 22.0 ± 0.2 mm Hg. The predicted COP based on the four different formulas was positively correlated with the measured COP (0.87 r 0.89), but was significantly overestimated compared to it (P 0.001). We also performed a stepwise analysis using serum albumin and non-albumin protein concentrations and obtained the following simple formula for COP approximation: COP (mm Hg) = -7.91 + 5.64 × albumin (g/dL) + 3.00 × non-albumin proteins (g/dL). A positive linear correlation was observed between the measured COP and approximated COP using this formula (r = 0.90, P 0.001). We calculated the mean Kr (plasma-refilling coefficient) as a marker for determining dry weight in HD patients using the measured COP and approximated COP. No differences were observed between the mean Kr derived from the measured and approximated COP. We report here significant differences between measured and predicted COP values, and have devised a simple formula for COP approximation in HD patients.

The incidence of cholesterol crystal embolism (CCE) has increased along with increases in the prevalence of atheromatous diseases and intravascular procedures. CCE frequently results in the deterioration of renal function, which sometimes leads to end-stage renal failure. Although there has been no established therapy for CCE, the possibility that low-density lipoprotein apheresis (LDL-A) is an effective therapy for renal CCE was previously reported. However, whether LDL-A improves renal CCE remains uncertain. This study aimed to evaluate the effectiveness of LDL-A in renal CCE patients. Twelve renal CCE patients (9 men and 3 women, mean age 70.6 ± 1.7 years) were included in this retrospective study. All patients had received LDL-A therapy, and estimated glomerular filtration rate (eGFR) values were examined before and after LDL-A. In addition, monthly changes in eGFR before and after LDL-A were calculated for each patient. At initial diagnosis of renal CCE, the eGFR was 35.2 ± 4.8 mL/min/1.73 m(2). At the initiation of LDL-A, the eGFR significantly decreased to 11.0 ± 1.2 mL/min/1.73 m(2), and monthly changes in eGFR reached -7.2 ± 2.5 mL/min/1.73 m(2)/month. After the initiation of LDL-A, the progression of renal dysfunction stabilized in nearly two-thirds of patients, and monthly changes in eGFR after LDL-A significantly diminished to -0.3 ± 0.7 mL/min/1.73 m(2)/month (p < 0.05 vs. before LDL-A). Although 4 patients had to undergo hemodialysis, all patients were alive over 1 year after the initiation of LDL-A. LDL-A therapy ameliorated renal dysfunction in renal CCE patients.

In healthy subjects, the blood volume (BV) increases rapidly after postural change from standing to the supine position. However, little is known about the effect of postural change on BV in long-term hemodialysis (HD) patients. Therefore, we have examined the BV change caused by adopting the supine position from standing by continuous hematocrit monitoring, using the CRIT-LINE instrument, in 8 anuric HD patients. The hematocrit was monitored for 25 min with the patient in the supine position just before HD. The percentage change in the BV (% Δ BV) was calculated from the hematocrit and approximated using the equation: % Δ BV = b – [1 – exp(–c × time (min)] –a × time (min). Coefficient a was the slope of the linear part in the % Δ BV, b was the magnitude of BV increase and c was the rate of BV increase. Then we examined the relationship between the coefficients (a, b and c) and clinical parameters. In all patients, % Δ BV increased quickly after adopting the supine position. The mean increases were 2.8 ± 0.6% after 5 min and 4.8 ± 0.5% after 25 min. There was a significant correlation between the value of % Δ BV calculated from the hematocrit and the value calculated using above equation (0.92 < r < 0.99, p < 0.001). Although coefficient a did not correlate with a clinical parameter, coefficient b showed a significant positive linear correlation with the serum albumin level (r = 0.816, p < 0.05) and coefficient c showed a significant positive linear correlation with the percentage change in interdialytic weight gain (r = 0.736, p < 0.05). Furthermore, based on the % Δ BV, we calculated the change in total BV, which had increased by 181.5 ± 21.9 ml after 25 min in the supine position. In conclusion, the change in the BV with time by continuous hematocrit monitoring using the CRIT-LINE instrument can be approximated by a modified monoexponential equation. BV increased quickly in HD patients after postural change from standing to the supine position.

目的: plasma refilling coefficient (mean Kr) はHD施行中の血管透過性を表すものとして近年, 提唱された新たな指標である. 今回, mean Krがドライウェイトの設定に有用であるか否かについて検討した.対象および方法: 安定維持HD患者41例で12か月にわたりHD前後の体重とともにHD前のヘマトクリット, HD前後血清総蛋白濃度を測定し総計446回のmean Krを得た. 得られたmean Krを0

Type 2 diabetic kidney disease (DKD) is frequently accompanied by uncontrollable hypertension due to the sodium sensitivity inherent in DKD and to diuretic-resistant edema. In general, diuretics are effective in treating this condition, but thiazide diuretics are thought to be innocuous in advanced chronic kidney disease (CKD). We examined the renoprotective effects of combination therapy with thiazides and loop diuretics in type 2 DKD patients with CKD stage G4 or G5. This study included 11 patients with type 2 DKD and an estimated glomerular filtration rate (eGFR)

目的: HD前後の血漿総蛋白濃度 (TP) 測定より算出される循環血漿量変化率 (%ΔCPV) のドライウェイト (DW) 設定の指標としての有用性を検討し, さらに%ΔCPVと血管透過性との関連についても検討した.対象および方法: 安定維持透析症例54名において, HD前後でTPを測定し%ΔCPVを算出した. %ΔCPVとHD施行中における時間あたりの体重変化率 (%ΔBW/h) の間には有意な負の相関を認め, 回帰直線の+5%以上 (Group 1; 除水にても比較的循環血漿量の減少が少ない群), ±5%内 (Group 2; %ΔBW/hより循環血漿量の減少がおおよそ推定できる群), -5%以下 (Group 3; 除水により循環血漿量の低下が著しい群) の3群に分け, 検討を行った. さらに%ΔCPVと血管透過性に関しても検討した.結果: 1) CTRは, Group 1はGroup 3に比し有意に大きく, Group 1のDWの設定が高い可能性があることを示唆していると思われた. また, HD前後での平均血圧変化率 (%ΔMAP) は, Group 3はGroup 1, Group 2に比較して有意に変化率が大きい, すなわちHD前に比しHD後に平均血圧が低下した. このことはGroup 3ではDWの設定が低すぎるか, plasma refillingの能力に比し除水速度が大きすぎるために血圧低下をきたしていると考えられた. 2) plasma refilling rateおよび血管透過係数 (Kr) はともに3群間でそれぞれ有意差を認めた. 3) 血管透過性とANPとの関連においては, plasma refilling rateとΔANPは有意の正相関を示した.結論: HD前後でのTP測定より求められる%ΔCPVはCTRおよび%ΔMAPを反映することよりDW設定の新たな指標になりうると思われた. また, %ΔCPVは血管透過性の影響を受けている可能性が示唆された.

目的: CRIT-LINE (In-Line Diagnostics社製) で観察した血液透析中の循環血液量の変化パターンを数学的に解析した.対象および方法: 安定維持透析患者8名にCRIT-LINEを装着し各5回ずつの血液透析を施行し, それぞれでヘマトクリットを計測し%BVを算出した. この%BVをy=b×[1-exp(cX)]-aXで回帰する方法を検討し, さらに各係数と臨床的パラメーターとの相関を検討した.結果: 1) ヘマトクリットは透析開始直後より一旦は低下し, 開始後約1時間より終了まで上昇した. %BVは透析開始直後より一旦は増加するものの開始後約1時間より終了まで直線的に減少した. 2) %BVの直線部分をy=b-aXで回帰すると, 相関係数0.95以上の密な相関が得られた. また, %BVの曲線部分 [%BV-(-aX)] をy=b×[1-exp(cX)] で回帰すると直線部分の回帰と同様に密な相関が得られた. 3) 以上より%BVの変化曲線はy=b×[1-exp(cX)]-aXで回帰できることが明らかとなった. 4) 直線の傾きを表す係数aは0.0859±0.0051, 直線の切片である係数bは5.948±0.433, 初期の循環血液量の増加速度である係数cは-0.0396±0.0028であった. 5) 各係数と臨床的パラメーターとの相関を検討したところ, 係数aと除水量が弱い相関 (r=0.50, p

Background/Aims: Patients undergoing hemodialysis (HD) have higher occurrence rates of cerebral diseases, including uremic encephalopathy, cognitive impairment, dementia, and cerebrovascular disease, than the general population. During HD, ultrafiltration is performed to maintain an adequate fluid condition and is associated with subsequent blood volume (BV) reduction. We aimed to (1) monitor changes in cerebral oxygenation and BV reduction during HD, and (2) clarify the mechanism that influences cerebral oxygenation in HD patients. Methods: Eighteen HD patients and 12 healthy controls were recruited. Regional saturation of oxygen (rSO2) was continuously monitored in the frontal cortex using INVOS 5100C before, during, and after HD, and in healthy controls. Relative change in BV (%ΔBV) was simultaneously monitored during HD using a BV monitor. Results: Before HD, patients had significantly lower rSO2 values than controls (56.1 ± 1.4 vs. 70.4 ± 2.5%, p < 0.001). Although %ΔBV significantly decreased from 20 min to the end of HD (20 min: -3.3 ± 0.3%, p < 0.05; end of HD: -12.0 ± 1.0%, p < 0.01), changes in rSO2 values during HD were not significant. No relationship existed between rSO2 values and blood pressure levels, hemoglobin levels, oxygen pressure, HCO3- , oxygen saturation, and arterial O2 content before and after HD. Furthermore, changes in rSO2 were not correlated with changes in these parameters. Conclusion: rSO2 values before HD were significantly lower in HD patients than in healthy controls. rSO2 values were maintained during HD and were not influenced by BV reduction.

A 74-year-old woman had been treated conservatively for type 2 diabetes mellitus (DM) and DM nephropathy since 2004. Her renal function gradually deteriorated, and she developed chronic renal failure (CRF) with a serum creatinine level between 2.5 and 3.0 mg/dl in 2010. She presented to our hospital with nausea and vomiting related to the progression of CRF in May 2011. An abdominal computed tomography (CT) scan showed distention of the upper digestive tract from the stomach to the third portion of the duodenum, ascites, and compression of the duodenum by the abdominal aortic artery and the overlying superior mesenteric artery (SMA), which was caused by edema along the gastrointestinal tract, in particular, at the duodenum. Therefore, she was diagnosed with SMA syndrome. Decompression of the distended upper digestive tract was achieved using a nasogastric tube, and hemodialysis was also initiated in order to adequately control her fluid balance disorder, which was thought to have induced the duodenal edema and ascites. After initiating these treatments, her condition gradually improved, and she fully recovered after approximately 2 months of treatment. Thus far, there has been no report of SMA syndrome caused by duodenal edema associated with the progression of CRF that was successfully treated by conservative treatment and the initiation of blood purification.

敗血症性ショックに対する治療として, エンドトキシンの選択的除去を目的としたポリミキシンB固定化ファイバーによる吸着療法 (PMX) の有用性, および臨床成績について生存群と死亡群に分け, 比較検討した. 対象は, 1994年5月より1995年2月までにPMXを施行した10例 (生存群6例, 死亡群4例). 全例, 明らかな感染巣を有し, ショック状態を呈し, 敗血症以外の原因が除外され, さらに感染巣への処置に加え, 抗生剤投与, 補液, 昇圧剤投与を施行しても治療に反応不良であった. 原疾患は, 腹部疾患が7例と最も多かった. ショック発現時よりPMX開始までの時間は有意差は認めないが死亡群で長い傾向であった. PMX開始時の状態の比較として, 感染症の重症度を表すseptic severity scoreでは有意差を認めなかったが, 不全臓器数を表すGorisのMOF基準では死亡群が有意に重症であった. 血液・生化学検査値の比較では, 血清クレアチニンのみが死亡群で有意に上昇していた. PMX開始時より24時間までの心拍数, 平均血圧, 時間尿量の比較では, 心拍数は両群ともに改善傾向を示し, 平均血圧ではPMX開始直後より生存群で有意な改善を認めたが死亡群では改善を認めなかった. 時間尿量では, 生存群は死亡群に比し, PMX開始前より有意に尿量が保たれており, PMX施行によりその差は著明になった. また生存群ではPMX施行直後より有意な増加を認めたが死亡群では改善を認めなかった. PMX開始前における予後推定因子の検討では, 時間尿量が30ml/hrより多い症例で有意に救命率が高かった. 以上の結果より, PMXは敗血性ショックに対し有効な治療法であるが, 施行するタイミングは臓器不全が進行する前, 時間尿量が30ml/hrを下回らない時点が適当と思われた.

蛋白分解酵素阻害薬, メシル酸ナファモスタット (nafamostat mesilate; NM) により高カリウム (K) 血症をきたした2症例を経験したので報告する. 症例1は, 51歳, 女性. 原発性アミロイドーシスより腎不全をきたし, 平成元年5月より血液透析導入となった. 同年9月19日より慢性膵炎急性増悪のためNM 150mg/日を投与したところ, 血清K値が4-5mEq/lから, 翌朝に7.0mEq/l, 翌々日に7.2mEq/lまで上昇した. その後膵炎症状が軽快したため, 21日後にNMを中止したところ, 22日には血清K値の低下を認め, その後, 以前と同様の推移に復した. 症例2は, 76歳, 男性. 平成5年12月10日, 解離性大動脈瘤 (Stanford A, 早期血栓閉塞型) を発症し, 降圧療法にて保存的治療を施行中であったが, 12月19日肺炎を併発したため, イミペネム/シラスタチンナトリウム2g/日投与を開始したところ, 急激な腎機能悪化を認め, 同剤を中止するとともに血中からの薬剤除去を目的に12月22日より持続血液濾過透析を開始した. 抗凝固剤としてはNM 30mg/時を使用した. その後, 徐々に血清Kの上昇を認め補液からのK投与を中止し, さらに透析液流量を増加させたが, 血清K値はさらに上昇した. 12月23日持続血液濾過透析を中止し, NM投与も中止したところ, 翌日より血清Kの低下を認め, その後も上昇を認めることはなかった. 症例1, 2ともNM投与が血清K上昇の原因と思われたが, 症例1は無尿状態で, 血清Kの上昇にNM, およびその代謝産物の腎でのK排泄に対する作用の関与はないと思われた. 症例2では, NM投与中のKバランスの検討では体内よりおよそ110mEqものKが透析により除去されていた. 以上より2症例とも高K血症の原因としてNM, およびその代謝産物の腎外性K調節系への関与が強く疑われた.

AIM To evaluate the lower-limb muscle oxygenation in hemodialysis (HD) patients and identify the factors associating with muscle oxygenation. METHODS Sixty-seven HD patients (53 men and 14 women; mean age, 67.1 ± 1.2 years; mean HD duration, 5.6 ± 0.9 years) were recruited. In addition, 15 healthy individuals (nine men and six women; mean age, 38.2 ± 4.6 years) were recruited as the control group. Lower-limb muscle regional saturation of oxygen (rSO2) was monitored on the lateral side of the gastrocnemius muscle before HD using an INVOS 5100C (Covidien Japan, Tokyo, Japan), which utilizes near-infrared spectroscopy. Here, we evaluated the association between lower-limb muscle rSO2 and clinical parameters. RESULTS The rSO2 values were significantly lower in patients undergoing HD than in healthy individuals (50.0% ± 1.7% vs 76.8% ± 2.5%, P < 0.001). Lower-limb muscle rSO2 showed significant positive correlations with diastolic blood pressure, blood urea nitrogen concentration, serum creatinine concentration, serum potassium concentration, serum inorganic phosphate concentration, and serum albumin concentration as well as negative correlation with HD duration. We conducted a multiple linear regression analysis using parameters that were significantly correlated with the lower-limb muscle rSO2 in a simple linear regression analysis. Multiple regression analysis demonstrated that lower-limb muscle rSO2 was independently associated with serum inorganic phosphate (standardized coefficient: 0.27) and serum albumin concentrations (standardized coefficient: 0.24). In addition, there were no differences in lower-limb muscle rSO2 between diabetic and non-diabetic HD patients. This study has several limitations. Firstly, its sample size was relatively small. Secondly, we could not evaluate the association between lower-limb muscle rSO2 and calculated nutritional markers, including normalized protein catabolic rate and body mass index, anthropometric measurements representing nutritional status, and the severity of protein-energy wasting. Finally, we did not routinely examine the arterial vascular status of HD patients without symptoms of peripheral artery disease. As such, it is possible that some HD patients with subclinical peripheral artery disease may have been included in this study. CONCLUSION In HD patients, the oxygenation of lower-limb muscle tissue was associated with serum inorganic phosphate and albumin concentrations, both of which represent nutritional status.

Together with Nikkiso in Shizuoka, Japan, we developed a new method for measuring the rate of vascular access recirculation by the blood volume monitor. This measurement is performed via a method of dilution that employs a marker produced by rapid ultrafiltration using a dialysis machine. In this paper, we evaluate the reliability and safety of this machine, in vitro and in vivo. The safety of this method was evaluated by investigating hemolysis after rapid ultrafiltration. The measurement of free hemoglobin, potassium and haptoglobin in the circulating blood were performed before and after rapid ultrafiltration. No data was found to indicate hemolysis in vivo, detected by an increase in potassium or a decrease in haptoglobin. Evaluation of reliability in an experimental system was also performed on an in vitro recirculation system at a rate of 0, 10, 25, 50, and 70%. Almost all of the measured rates were within ± 10% of the theoretical rate. We performed 20 hemodialysis experiments with vascular access recirculation applying this monitor and simultaneous urea and creatinine dilution methods, which were the recommended standard measurements for vascular recirculation. In 53 measurements of standard vascular shunts with no postural change, differences of the results between the monitor and both dilution methods were only 4.0% and 3.2%, respectively. Regression analysis showed a significant and positive correlation between them (P0.0001). We conclude that this new method for measuring vascular access recirculation is applicable in terms of both accuracy and ease of operation.

We developed a new optical device (Nikkiso) to assess changes through blood volume monitoring (BVM) during hemodialysis and were able to determine the ideal levels in which changes in blood volume percentage (BV%) occur among hemodialysis patients in one hemodialysis center. We evaluated both the reliability of BVM and these ideal levels in a multicenter group. The purpose of this manuscript is to develop a navigating system to set dry weight in a variety of situations as the final goal. First, based on the obtained BVM (BV%(BVM) ) measurements, the relationships between BV% and hematocrit (BV%(HT) ) and between BV% and CRIT-LINE (BV%(CLM) ; Hema Metrics, Kaysville, UT, USA) were then evaluated. In 30 hemodialysis patients, there was a close correlation between both BV%(BVM) vs. BV%(HT) and BV%(BVM) vs. BV%(CLM) (n=30, r=0.967, P0.001, and n=36, r=0.7867, P0.001, respectively). Second, BV% data were obtained from 464 treatment cases performed on 26 subjects in one satellite hemodialysis center on patients whose body weight was deemed clinically suitable. The formulas for the levels of BV% (standardized by the percent change in body weight at the end of hemodialysis treatment: BW%end) were determined. Finally, we revalidated the reliability of the above levels. A total of 1126 measurements were performed on 201 patients whose body weights were deemed suitable in seven hemodialysis centers. New ideal levels were then recalculated. We therefore conclude that BVM is a sufficiently accurate method of monitoring BV% in hemodialysis treatment. Most well-controlled hemodialysis patients display the same pattern of BV%/BW%end. Monitoring BV% during hemodialysis is beneficial for determining dry weight (DW).

目的: 血液透析の際, 除水施行にもかかわらずHt, TPが低下する症例が存在するが, このことに立位から臥位への体位変換がどれだけ影響するかについて検討した. 対象および方法: 安定維持透析中の男性症例 (n=10) を対象に5分間立位後と30分間臥床後にHt, TPを測定し, 循環血液量変化率 (%ΔBV) を演算により求めた.結果: 1) 30分間臥床によりHt, TPはそれぞれ, 臥床直後32.6±2.1%, 6.68±0.12g/dlから30分間臥床後29.7±1.9%, 5.81±0.10g/dlと全例で有意に低下した. 2) 30分間臥床により%ΔBVは9.1±0.8%増加した. これは正常人を対照とした30分間臥床による%ΔBVの増加に比し有意に高値であった. 結論: Ht, TP, %ΔBVの評価において体位変換の影響を十分考慮する必要がある.

We report here the case of a patient suffering from hemophagocytic syndrome (HPS) associated with toxic shock syndrome (TSS). A 50-year-old man was admitted because of fever, watery diarrhea and shortness of breath. Clinical analysis revealed systemic cyanosis, sunburn-like erythema and septic shock. Staphylococcus aureus was identified from both blood and sputum culture and the serum enterotoxin A antibody test was positive, suggesting that this was a case of TSS. Though the respiratory and hemodynamic status improved by the mechanical ventilation, fluid resuscitation with catecholamine and antibiotic therapy, the platelet count decreased rapidly. Bone marrow aspiration revealed a large quantity of hemophagocytosis by macrophages. This reactive HPS was treated not with immunosuppressive drugs but with therapeutic plasma exchange in order to prevent worsening of S. aureus infection. After plasma exchange, the circulating macrophage colony-stimulating factor (M-CSF) level was reduced and the platelet count increased rapidly. Bacteria associated HPS remains a difficult diagnosis with high mortality and there is a crucial question of whether this should be treated with immunosuppressive drugs. The patient's clinical course would suggest that the therapeutic plasma exchange should be considered as a therapeutic tool for the bacteria associated HPS instead of immunosuppressive drugs.

Nafamostat mesilate, a potent protease inhibitor, is widely used for the treatment of pancreatitis, disseminated intravascular coagulation and as an anticoagulant in haemodialysis. However, hyperkalaemia associated with nafamostat mesilate has been reported. It is thought to be due to decreased urinary potassium excretion, of the drug suppression of aldosterone secretion, and a direct inhibitory action on the apical Na+ conductance in collecting ducts. We have seen two cases of nafamostat mesilate associated-hyperkalaemia, which indicated that extrarenal potassium imbalance might play a role in inducing hyperkalaemia.To examine the effect of nafamostat mesilate on potassium transport in erythrocytes in vitro, 86RbCl uptake was measured in red blood cells from eight healthy volunteers.Nafamostat mesilate and a metabolite, 6-amidino-2-naphthol, at concentrations of 10(-4) and 10(-3) M, respectively, significantly, suppressed potassium influx whilst another metabolite, p-guanidino-benzoic acid, had no effect. The inhibitory action of nafamostat mesilate was not affected by various inhibitors.Nafamostat mesilate and its metabolite, 6-amidino-2-naphthol, suppressed potassium influx in erythrocytes by inhibition of a Na-K ATPase dependent pathway, which was not inhibited by amiloride, barium, nor by frusemide (furosemide).

Epidermal growth factor (EGF) inhibits amiloride-sensitive Na+ conductance in the apical membrane of the isolated rabbit cortical collecting duct. However, there is no information on the relationship between electrolyte transport and tyrosine kinase. We examined the effect of EGF on transport of potassium and chloride as well as sodium and the roles of tyrosine kinases in the rabbit cortical collecting duct using in vitro isolated tubular microperfusion. Basolateral EGF depolarized the transepithelial voltage in a dose-dependent manner within a concentration range of 10−10 in 10−8 M. Basolateral ouabain and luminal amiloride completely abolished EGF-induced depolarization. However, luminal BaCl2 did not abolish its depolarization. To confirm the mechanism, sodium, potassium, and chloride fluxes were measured in the presence of 10−10M EGF. EGF significantly decreased the lumen-to-bath isotope flux of sodium and chloride from 93.6±12.5 to 61.1±9.6 pmol/mm/min (n = 5, p+ absorption on EGF action (control 65.4±6.8, herbimycin A 61.8±6.3, EGF with herbimycin A 60.0±4.4 pmol/min/mm, n = 5; NS). In conclusion, EGF depolarizes transepithelial voltage by inhibiting sodium transport primarily and potassium and chloride transport secondarily. These effects were blocked by nonspecific tyrosine kinase inhibitors.