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Recombinant human erythropoietin (rHuEPO) is used to correct anemia in the majority of hemodialysis patients, but a few patients can maintain greater hematocrits without the use of rHuEPO. We aim to investigate which factors stimulate erythropoiesis, other than rHuEPO, in hemodialysis patients. One hundred fifty-eight patients undergoing regular hemodialysis treatment participated in a cross-sectional study. To keep the target hematocrit of 30%, 133 patients (84%) were administered rHuEPO, but 25 patients (16%) did not need rHuEPO. Mean hematocrits were 33.4% +/- 4.6% in patients who did not need rHuEPO and 30.9% +/- 4.0% in those administered rHuEPO. In the analysis of factors contributing to the lack of requirement of rHuEPO with multivariate logistic regression analysis, years on dialysis therapy and body mass index (BMI) were determined to be independent factors with odds ratios of 1.12 (95% confidence interval [CI], 1.02 to 1.23; P = 0.02) and 1.36 (95% CI, 1.13 to 1.63; P = 0.001), respectively. Neither serum erythropoietin level, albumin concentration, nor normalized protein catabolic rate contributed to the lack of requirement of rHuEPO. BMI correlated closely with log serum leptin level (r = 0.55; P < 0.0001), and log serum leptin level correlated inversely with rHuEPO dose (r = -0.18; P = 0.03). These results indicate that 16% of hemodialysis patients could maintain greater hematocrits without the administration of rHuEPO, and independently contributing factors were greater BMI and more years on hemodialysis therapy. Regarding nutritional parameters, a relatively greater BMI, possibly through effects of greater leptin levels, may stimulate erythropoiesis in uremic patients even in the absence of sufficient erythropoietin production.

抗凝固薬および血小板凝集抑制薬を内服していない慢性維持透析患者を対象とし, 各種透析器におけるヘパリンの最低必要量について比較検討した結果, PSが最も多く, 以下KF, PAN, B2, TF, PC, SD, FBの順であった. また最低必要量の多いKF, PSについて血液ポート角度を従来の18度から7度に変更したものを比較したところポート部での血液の乱流や滞留が改善され最低必要量は有意に減量できた.ヘパリンの最低必要量は使用する透析器により明らかに異なり, 血液ポート部形状にも大きく左右される. よって膜素材だけでなくハウジングデザインの選定も透析器の抗血栓性において重要である.

エンドトキシンによる透析液汚染と患者への影響をみるため, 透析液供給システムの再検討を行った. 当院の処理水, Bicarbonate原液タンク (B原液タンク), 透析液をトキシカラー (TC) 法およびエンドスペーシー (ES) 法でそれぞれ測定した. さらに室温の変動による細菌発生の差異をみるため, 冬期および夏期についても比較検討した. エンドトキシン抗体の測定はenzyme-linked immunosorbent assay (ELISA) 法にて, 通常透析膜 (LOW FLUX) とハイフラックス膜 (HIGH FLUX) それぞれの使用者20名を対象とした. 1年を通じてB原液タンクの細菌による汚染がもっとも大きく, エンドトキシン濃度も高値であった. 特に気温の高い夏期では極めて高濃度となり, 原液タンクサプライ方式による透析ではエンドトキシンフリー透析液供給は困難であることが確認された. さらにエンドトキシン抗体の陽性率比較ではLOW FLUXに比し, HIGH FLUX使用者側がχ2の検定により有意に高率であった. これらの結果から透析液清浄化に向けての対策が必要であり, タンク内洗浄の強化とパイロジェン除去フィルターなどの設置が有効な手段と示唆された.

Background: Hemodialysis patients are at significantly increased risk for both morbidity and mortality from cardiovascular disease. However, most recent reports have indicated elevated mortality risk associated with low blood pressure, rather than high blood pressure. We added nonfatal cardiovascular events as an outcome in addition to cardiovascular and all-cause mortality to analyze the risk of hypertension. Methods: One hundred sixty-four patients receiving regular hemodialysis between January and December 1998 were examined and prospectively followed up until the end of 2003. The primary end point was hospital admission or death from cardiovascular disease. Secondary end points were cardiovascular and all-cause mortality. Results: During the 5-year follow-up period, 52 patients experienced cardiovascular events and 45 patients died (18 patients, from cardiovascular disease). Based on Cox analysis, high systolic blood pressure (relative risk [RR], 1.23; 95% confidence interval [CI], 1.07 to 1.43; P = 0.004) and older age were independently associated with cardiovascular events. Elevated systolic blood pressure (RR, 1.25; 95% CI, 0.99 to 1.59; P = 0.063) was a marginal predictor for cardiovascular mortality. Age, serum albumin level, malignant neoplasm, and diabetes were independent risk factors for all-cause mortality, whereas there was no association between blood pressure and all-cause mortality. The hazard ratio for cardiovascular events after adjustment for age, sex, and diabetes was lowest in patients with systolic blood pressure of 140.1 mm Hg or less and progressively increased with the increase in systolic blood pressure. Conclusion: Hypertension is a potent risk factor for cardiovascular disease in hemodialysis patients, as in the general population, whereas there is no association of hypertension with mortality. Active reduction in systolic blood pressure is important to minimize the occurrence of cardiovascular events.

Quasi-steadiness approximation for the single-compartment urea kinetic model (SCUKM). Using SCUKM, we constructed recurrence formulae expressing weekly pre- and post-dialysis urea levels. Then we mathematically derived simple methods to estimate Kt/V 0 and the urea generation rate (G) per unit urea distribution space post-dialysis (V 0 ), which only required the measurement of pre- (C) and post-dialytic blood urea concentrations (C 0 ) of a single hemodialytic session (two-point method). Underlying fundamental assumptions were: (i) patients receive weekly scheduled hemodialyses; (ii) the ultrafiltration rate, intradialytic urea generation, interdialytic water increase rate, and residual renal function are small enough to be retained only as the leading term in the formulae. In the derivation, we proved relations: C=f(Kt/V 0 )G/V 0 , and C 0 = g(Kt/V 0 )G/V 0 , which state that both C and C 0 are directly proportional to G/V 0 , and that the proportional constants are functions of Kt/V 0 . Errors of the formulae were also checked to make the limitation of the approximations clear. The present formulae exactly reproduced Kt/V 0 and G/V 0 of virtual patients strictly obeying the SCUKM in a computer simulated model. Using the blood urea nitrogen concentration data of 20 actual patients, we compared our method with the usual three-point method and obtained substantial correlations between them ( r = 1.00 for Kt/V 0 , r = 0.98 for G/V 0 ). Finally, we proposed convenient and easily calculable new formulae, which give sufficiently accurate Kt/V 0 and G/V 0 .

The effects of recombinant human erythropoietin (rHuEPO) and exercise training on exercise capacity were evaluated in 20 hemodialysis patients. After improvement of anemia by rHuEPO (Phase I), patients were divided into 2 groups. Group 1, 10 patients, was placed in a 3-month exercise training program. Group 2, 10 patients, served as a control group (Phase 2). A symptom-limited exercise tolerance test was performed at the start of Phase 1 and before and after Phase 2. Hemoglobin (Hb) values were kept constant throughout Phase 2. In Phase 1, maximum workloads (62.0 +/- 19.1 to 76.5 +/- 25.6 W, p < 0.001), maximum O2 uptake (VO2max) (18.7 +/- 3.5 to 2.2 +/- 5.9 ml/min/kg, p < 0.01), and VO2 at anaerobic threshold (AT) (VO2AT) (8.5 +/- 2.1 to 10.2 +/- 2.9 ml/min/kg, p < 0.01) were all improved by rHuEPO. However, in Phase 2, despite unchanged Hb values and maximum workloads, VO2max (20.7 +/- 4.6 to 17.6 +/- 2.6 ml/min/kg, p < 0.05) and VO2AT (10.6 +/- 1.4 to 9.5 +/- 1.8, ml/min/kg p < 0.05) were decreased in Group 2. However, in Group 1, maximum workloads (66.7 +/- 8.2 to 81.7 +/- 7.5 W, p < 0.01) were improved, and VO2max and VO2AT were not decreased significantly in the same period. Exercise training in rHuEPO-treated hemodialysis patients resulted in an improved aerobic exercise capacity, whereas those without exercise training did not have increased capacity. Throughout the study, O2 uptakes were lower than those of nonrenal anemic patients who had similar Hb values. Maximum lactate values also remained low. In conclusion, improvement in the exercise capacity in hemodialysis patients treated with rHuEPO was minimal. Some defects were suggested in the aerobic energy production system in skeletal muscle of dialysis patients. Anemia-improved patients should participate in incremental physical activity to maintain an improved exercise capacity.

A 51-year-old woman with primary biliary cirrhosis developed distal renal tubular acidosis and hypouricemia (1.4 mg per 100 ml) in the course of hepatic injury. Her renal clearance of uric acid reached 33.7 ml/min (mean +/- SD in five normal age-matched women: 9.2 +/- 3.1 ml/min). Pyrazinamide, an inhibitor of uric acid secretion, considerably reduced the uric acid clearance, while it was not enhanced by probenecid, a blocker of uric acid reabsorption. Thus, the hypouricemia may have been due to a defect of postsecretory reabsorption of uric acid in the renal tubules. The present case emphasizes the significance of hypouricemia and hyperuricosuria as indicators of renal tubular injury in primary biliary cirrhosis.

神経学的所見および神経伝導速度を用いて手根管症候群の早期診断法について検討を加えた. 対象は5年以上血液透析を受けている52名 (男36名, 女16名) の患者で, 平均年齢48±12歳, 平均透析期間8.5±2.6年である. 各患者の両手につき, 手のしびれ, 疼痛などの自覚症状, Tinel's sign, Phalen testなどの神経学的所見, 正中神経, 尺骨神経のdistal motor latency (DML), 正中一尺骨神経DMLの差 (median-ulnar difference), 四肢のmoter nerve conduction velocity (MCV) の測定をおこなった.その結果, 明かな自覚症状を有する手根管症候群 (A) の発症は4肢 (3.8%) であり, 自覚症状はないが神経学的に異常所見を有する群 (B) は17肢 (16.3%) であった. 自覚症状も神経学的異常所見もない群 (C) は83肢 (79.8%) であった. 正常control群に比してDMLはA群, B群, C群ともに高値を呈した. Median-ulnar difference値はcontrol群に比しA群, B群は有意の上昇を認め, C群では有意差を認めなかった. Median-ulnar differenceがMCVに影響されないのに対し, DMLは影響され, MCVの延長している末梢神経障害患者で延長した.結論として初期手根管症候群の診断にDML, median-ulnar differenceの測定は有用である. median-ulnar differenceはMCVの延長している長期透析患者においてもその影響を受けず, DMLに比しより診断に有用であると考えられた.

The mechanism of kaliuresis induced by massive antibiotic administration was studied using alpha-sulfobenzyl penicillin (SBPC). In experimental group (n = 8), urinary electrolytes excretion were compared between following the infusion of 10 g SBPC in 200 ml water at a constant rate and following the infusion of 48 mmol of NaCl (equal to that contained in 10 g SBPC) in 200 ml water. For the control group, 96 mmol NaCl in 400 ml water was infused (n = 5). In the experimental group, urinary Na (UNaV) and urinary K excretion (UKV) increased relative to the control period. In the control group, UKV was not increased although UNaV was increased (p less than 0.05). UKV following SBPC infusion was correlated with UNaV (p less than 0.05) and urinary SBPC excretion (p less than 0.05). The ratio of urinary anion gap to urinary cation [1-(urinary Cl concentration/(urinary Na concentration + urinary K concentration))] was significantly increased following SBPC infusion (p less than 0.005) but not in the control group. This increase in anion gap is possibly due to urinary SBPC, which will be ionized over 90% as nonreabsorbable anion in maximally acidic urine. We conclude that the kaliuresis induced by massive SBPC administration in man is probably caused by the nonreabsorbable anion effect of SBPC itself.

血漿交換,ステロイドパルス療法が有効であった急速進行性賢炎を呈した結節性多発性動脈炎(PN)の1例を報告する.症例は69才,男性.主訴は発熱,筋肉痛および腎機能低下.腎生検にて50%以上の糸球体の半月体形成と間質の細胞浸潤が,筋肉生検にて血管炎の所見が得られた. microscopic PNと診断し血漿交換,ステロイドパルス療法を施行したところ,血中免疫複合体は消失し,臨床症状,腎機能および組織学的にも著明な改善が認められた.急速進行性腎炎を呈したPNに血漿交換,ステロイドパルス療法を施行した報告は少なく,文献的考察を加えて報告する.

1. Baroreflex sensitivity was evaluated in 22 non-dialysed patients with chronic renal failure secondary to chronic glomerulonephritis. Baroreflex sensitivity was judged by the slope of the linear regression of the pulse interval on the rise in systolic blood pressure with injection of phenylephrine or reduction by amyl nitrite inhalation. 2. Baroreflex sensitivity was reduced in these patients as compared with normal controls. Reduction of baroreflex sensitivity was significantly greater in nine hypertensive than 13 normotensive patients with chronic renal failure. 3. A significant positive correlation was found between baroreflex sensitivity and motor nerve conduction velocity measured on ulnar nerve in 13 patients examined. 4. Saline was given with high dietary salt intake to seven normotensive patients with chronic renal failure for 2 or 5 days in order to determine whether the severe depression of baroreflex sensitivity can be an initiating factor for hypertension. Blood pressure was raised to hypertensive levels within 5 days in two patients in whom baroreflex sensitivity was nearly as low as that of hypertensive patients, but not in five cases whose baroreflex sensitivity was normal or only mildly depressed. Plasma volume increased to the same degree in both groups. Baroreflex sensitivity did not change in the former two cases despite blood pressure elevation. 5. It is concluded that reduced baroreflex sensitivity in chronic renal failure correlated with the presence of hypertension, as well as uraemic neuropathy, and may be one of the pathogenetic mechanisms of hypertension in end-stage chronic glomerulonephritis.

症例は72才,男性で,悪心・嘔吐,食欲不振にて当科に入院した.低Na血症(117mEq/l)を認め,血清浸透圧244mOsm/kgに対し,尿浸透圧は662mOsm/kgと高く,血漿ADHは3.1pg/mlと抑制されていなかった.水負荷試験にて尿浸透圧の低下は見られず,血漿ADHも抑制されず,排泄率19%と水排泄障害を認めた.以上よりSIADHと診断した.原疾患は,胸部X線写真より右肺上葉の肺癌が疑われ,肺生検で擦過細胞診より扁平上皮癌と診断した.右上葉切除術を施行し,術後, SIADHは寛解した,腫瘍組織内ADR含量測定,腫瘍組織培養,間接酵素抗体法等よりADH産生肺癌であることを証明した. ADH産生肺扁平上皮癌の報告は極めてまれで,本邦こおいて本例が2例目である.

A 36-year-old man was admitted because of sopor and dark urine after intravenous amphetamine injection. He subsequently developed myoglobinuria and acute renal failure. Serum myoglobin value was remarkably elevated to 83,000 ng/ml, and urine myoglobin was 400,000 ng/ml. Renal biopsy revealed tubular degeneration and tubular obstruction with myoglobin casts by immunofluorescence examination. Amphetamine-induced rhabdomyolysis was suspected to cause myoglobinuric acute renal failure.

A 65-year-old woman with mild renal insufficiency had persistent hyperkalemia and hyperchloremic acidosis. Her plasma aldosterone level was relatively low for her hyperkalemia, and her urine pH was low. Fludrocortisone acetate administration corrected both hyperkalemia and acidosis by increasing urinary excretion of potassium and net acid, implicating deficient mineralocorticoid activity in the distal renal tubule in this patient. During this medication urinary ammonium excretion increased, but urine pH remained low, so that urinary titratable acid excretion did not decrease. On the other hand, correction of hyperkalemia by administration of a potassium-calcium exchange resin alone also resolved the acidosis by increasing urinary ammonium excretion. This increment exceeded the decrement of urinary titratable acid excretion, which was caused by raised urine pH secondary to increased urinary ammonium excretion, and resulted in increase of net acid excretion. Thus, in this patient, hyperkalemia appears to be a decisive causative factor in the acidosis, with deficient mineralocorticoid effect only contributing in part to the reduction of net acid excretion and the acidosis.