Makoto Yamakawa

Clinical Effects of Long-Term Use of Neutralized Dialysate for Continuous Ambulatory Peritoneal Dialysis

The long-term effects of neutralized dialysate used in continuous ambulatory peritoneal dialysis (CAPD) were evaluated in 8 well-controlled patients. Twelve milliliters of 8.4% sodium bicarbonate was added to Dianeal PD-1 immediately before every administration. The final pH was 6.8 and the concentration of sodium bicarbonate was 6 mmol/l. The final sodium level was 138 mEq/l. This dialysate was used for 5 months. For 2 months before and 3 months after this period, Dianeal PD-2 was used as the dialysate for comparison. Blood bicarbonate levels significantly improved during the use of the neutralized dialysate. Blood sodium, chloride and magnesium levels and the effluent volume significantly increased. Sodium balance improved during the period when neutralized dialysate was used. Total leukocyte counts in the effluent decreased, and leukocyte viability increased. Abdominal distention, abdominal pain during instillation, nausea and headache improved. No side effects, including peritonitis, occurred during the trial of neutralized dialysate. The results suggest that this dialysate was less irritating to the peritoneal membrane than the control dialysate and that the therapeutic effects were satisfactory.

Serum Levels of Acetate and TCA Cycle Intermediates during Hemodialysis in Relation to Symptoms

In order to study the metabolism of acetate transferred from dialysate, the plasma concentrations of organic acids including the tricarboxylic acid cycle (TCA cycle) intermediates were measured during hemodialysis in a comparative study between acetate dialysate and bicarbonate dialysate in 17 patients on maintenance hemodialysis treatment. Continuous measurements of serum concentrations of these organic acids during hemodialysis were performed using the filtrate obtained through an ultrafiltrate sampling device. The organic acids were measured by isotachophoresis. Serum acetate, malate and citrate concentration increased with time in acetate dialysis compared with bicarbonate dialysis. Correlations were found between these organic acids. Isocitrate became detectable when the serum acetate concentration was over 7 mmol/l which was correlated to the acetate concentration, and was accompanied by the development of symptoms. The above results suggest that an acetate overload on the patients during acetate dialysis affects acetate metabolism through the TCA cycle resulting in an accumulation of organic acids in the serum and the development of symptoms.

Decreased Bone Mineral Density in Diabetic Patients on Hemodialysis

Renal osteodystrophy in hemodialyzed patients with DM-HD shows different features from that in non-DM,HD. Two studies were done. One was a comparison of BMD in 30 non-DM,HD patients and 30 DM-HD patients. The second was a comparison of possible factors affecting calcium metabolism in the higher and lower BMD groups (n = 20/21) in the DM-HD patients. BMD was measured by dual-energy X-ray absorptiometry (DEXA; Hologic QDR 1,000/W) in the third lumbar vertebra (L3), head, pelvis, and whole body. The BMDs of the DM-HD group were lower in these areas and whole body than that in the non-DM,HD group. A significant difference was found in the head BMD (p less than 0.05). In the second study, factors which may contribute to the differences in BMD were compared in the DM-HD patients divided into higher and lower BMD of the head. The group with higher head BMD had a value 110% of the mean value or more. Clinical and biochemical test results (age, the time since the first dialysis, body weight, the degree of obesity, height, serum calcium, serum phosphate, serum aluminum, serum c-PTH level and the dose of 1 alpha-OH-D3) were compared. The degree of obesity of the patients with higher BMD was significantly larger than that with lower BMD (p less than 0.005).

Concentrations of Thyroxine-Binding Globulin in Sera and Peritoneal Dialysates in Patients on Chronic Peritoneal Ambulatory Dialysis

Losses in thyroxine-binding globulin (TBG) in peritoneal dialysate and thyroid function were evaluated in patients undergoing continuous ambulatory peritoneal dialysis (CAPD), in comparison to patients on hemodialysis (HD) without TBG loss in the dialysate. The TBG concentration in the peritoneal dialysate was 0.26 +/- 0.09 microgram/ml (mean +/- SD, n = 24), with a daily loss of 2.47 +/- 0.94 mg. The serum TBG level in CAPD patients was 21.0 +/- 4.71 micrograms/ml (n = 24), which was not significantly different from that in HD patients (20.0 +/- 5.72 micrograms/ml, n = 24) or in healthy Japanese subjects. The serum TBG level correlated positively with the TBG loss and TBG level in the peritoneal dialysate (p less than 0.001). The serum T4 level in CAPD patients (4.93 +/- 1.38 microgram/dl, n = 24) was significantly greater than in HD patients (4.08 +/- 1.30 microgram/dl, n = 24, p less than 0.05).

Acetate Kinetics during Hemodialysis and Hemofiltration

A comparison was made between acetate dynamics in hemodialysis (HD) with acetate dialysate and hemofiltration (HF) using acetate substitution fluid. Acetate kinetics was calculated from removed HCO-3 (Rbc), generated HCO-3 (Gbc) and loaded CH3COO- (Lac) during each treatment. Rbc and Gbc were 99 ± 17 and 137 ± 18 mmol/h in HF, and 114 ± 23 and 128 ± 27 mmol/h in HD, respectively. Lac was 142 ± 25 mmol/h in HF and 162 ± 27 mmol/h in HD. Accordingly, the conversion rate (CR) from acetate to bicarbonate was 98 ± 18% in HF and 79 ± 9% in HD. Although the net load of acetate was comparable, CR was significantly greater in HF, resulting in a significantly smaller increment of the serum acetate level. Therefore, fewer symptoms are seen and better normalization of acidosis can be achieved in HF.

Periodic examinations of the upper gastrointestinal tract and abdominal ultrasonic examination in maintenance dialysis patients

長期透析患者における消化器系疾患の定期検診を行ない, その成績について報告した. 当院の透析患者延べ1404例を対象として, 上部消化管造影検査については1983年より5年間, 腹部超音波検査については1986年より2年間, 各患者の誕生月に, 年1回実施した. 上部消化管造影検査の平均受診率は55.5%, 有所見者についての内視鏡検査の平均受診率は30.7%であった. 5年間に胃潰瘍30例 (3.9%), 十二指腸潰瘍44例 (5.6%), 早期胃癌2例 (0.3%) を認めた. 腹部超音波検査の平均受診率は70.3%であった. 2年間に胆石34例 (7.6%), 胆嚢ポリープ15例 (3.4%), 肝臓癌1例 (0.2%) を認めた. 透析患者は自覚症状の少ない場合も多く, 早期発見のための定期検診の重要性を認識した.

Serum selenium concentration in patients with chronic renal failure

慢性腎不全患者の血清セレン (Se) 濃度と各臨床パラメーターの関係について検討した. 腎機能の正常なNormal群に比し, 透析導入前の慢性腎不全患者 (CRF群), 血液透析患者 (HD群), 連続的携行式腹膜透析患者 (CAPD群) の血清Se濃度は有意に低く, CRF群はHD群に比し有意に低かった. CRF群において血清Se濃度とHt値, 赤血球数の間にはそれぞれ有意の正相関が示され, CRF群のSe低下に貧血が関与していることが示唆された. またHD群, CAPD群ともに血清Se濃度とHD期間, CAPD期間の間にはそれぞれ有意の負の相関が示され, 透析期間の延長にともない血清Se濃度が低下することが示され, その低下の程度はCAPD群でより著しかった. 一方, 他のHD群においてHD後, 血漿Se濃度はHD前血清Se濃度に比し有意に高かったが, Ht値で補正すると有意差は認められなかった. しかしこのデータだけではHDによりSeが除去さ. れるかどうかは不明である. 慢性腎不全患者の血清Se濃度低下と臨床症状との関係は未だ不明であるが, 長期透析患者, 特に長期CAPD患者では血清Se濃度の低下が著しく, 癌発生のリスクの上昇, その他にも長期透析患者の合併症として考えられている筋肉痛, 免疫能低下, 冠動脈疾患などの発症のリスクが高まることが考えられる.

Acetate metabolism and uncomfortable symptoms induced by hemodialysis

酢酸透析中にみられる悪心, 嘔吐, 頭痛, 急激な血圧降下等の不快症状の原因の1つに, 透析液より体内への酢酸の大量負荷が考えられるが, 負荷された酢酸の代謝や作用機序及び不快症状との関係は不明である.我々は重曹透析患者を比較対象として, 酢酸透析中の血清acetate, lactate, pyruvate及びTCA-cycleの中間代謝物質を経時的に測定することによって, 負荷されたacetateの生体への細胞レベルでの影響を検討した.方法は重曹透析6名及び酢酸透析6名にそれぞれ1.1m2のHFKダイアライザーを用いて, 透析中の上記物質の血清濃度を経時的に測定した. また別に2.1m2の大面積ダイアライザーを用いた酢酸透析5名において不快症状の発現, 血圧, 脈搏を連続的に記録し, 血清acetate, malate, citrate及びisocitrateの濃度を連続的に測定した. 酢酸透析液は37mmol/lの酢酸ソーダをアルカリ剤として含み重曹透析液は25mmol/lの重炭酸ソーダと10mmol/lの酢酸ソーダを含んでいるものを用いた. またacetate lactate pyruvate及びTCA-cycle中間代謝物質の測定にはisotachophoresis (IP-1B, Shimadzu) を用いた.この結果, 重炭酸透析では透析中その値が殆んど変化せずに, 酢酸透析で経時的に且つ有意に増加をみたのはacetate, citrate, malateの濃度であった. isocitrateはacetate濃度が5mmol/lをこえて後に検出可能となった. これ等の物質の血清濃度相互間に相関々係を認めた. またacetate濃度の上昇, isocitrateの出現と不快症状発現との間に密接な関連があることが示された.以上のことより, 酢酸透析に伴う不快症状の発現は, acetateが患者体内にその代謝能力以上に負荷された結果生ずる代謝障害が原因であるということが推測された.

Studies of bicarbonate dialysate and effects of acetate in hemodialysis

酢酸の添加された重炭酸透析液について, 安定性と酢酸の生体への移行量測定を行ない, また重炭酸透析と酢酸透析を比較することにより, 重炭酸透析の臨床的効果と酢酸透析の生体の影響を検索した.対象は74名の慢性透析患者で, 研究は9mmol/lの酢酸を含む重炭酸透析液の多人数用供給装置での安定性、重炭酸透析と酢酸透析の生化学検査および愁訴発現頻度による長期臨床比較, 2重盲検交差試験による短期臨床比較, 酢酸の生体移行量測定に分けて施行された。その結果, 重炭酸透析液のpH, Pco2は安定しており, Ca濃度に関しても特に問題となることはなかった. 長期臨床比較では重炭酸透析に生化学検査の改善を認め, 酢酸透析に愁訴発現を高率で認めた. 2重盲検交差試験では重炭酸透析を酢酸透析に転換したことにより, 61%の患者に何らかの愁訴発現を観察し, 21%の患者はその症状が激しく透析時間を短縮せざるを得なかった. 酢酸の生体移行量測定は, 重炭酸透析液ではHFAK-2.1m2で0.41mmol/hr/kgであった.以上のことより, 重炭酸透析に添加された少量の酢酸は, 透析液, 生体側共に良好な緩衝剤となり, 生体で充分代謝できる量であることが示された. また酢酸透析は透析中の不快な愁訴発現に関連があり, 無症候透析という点で重炭酸透析よりすぐれていることが示された. 重炭酸透析は生化学検査でも酢酸透析と同等もしくはそれ以上の成績が得られ, 32か月間の使用にも副作用と思われることは認めなかった.