Seishi Inoue

Efficacy and safety of oral falecalcitriol in reducing parathyroid hormone in hemodialysis patients with secondary hyperparathyroidism

Abstract: Based on research conducted so far, active vitamin D3 is known to suppress the secretion of parathyroid hormone (PTH), which is stimulated by chronic renal failure. We investigated the effect and safety of falecalcitriol, a new type of active vitamin D3, in patients with secondary hyperparathyroidism accompanied by chronic renal failure in a multicenter study. In a double-blind study, 121 patients were randomly assigned to a falecalcitriol group (63 patients) or a placebo group (58 patients). They received daily oral falecalcitriol or placebo for 8 weeks. The change rates of intact PTH (i-PTH) , midregion PTH (m-PTH), and carboxy-terminal PTH (c-PTH) were determined as major evaluation parameters. The falecalcitriol group showed a significant suppression (P < .01) of 34.8% in i-PTH; in contrast, the placebo group recorded a significant rise (P < .01) of 12.4%, with a significant difference (P < .01) between the groups. The results for m-PTH and c-PTH were similar to those for i-PTH. Serum calcium, meanwhile, rose significantly (P < .01) in the falecalcitriol group after 2 weeks. The mean values, however, remained within the normal range, and the change rate was within 10%. Apart from the rise in serum calcium, there were no differences in adverse reactions from the placebo group. The results suggest that falecalcitriol is an effective drug against secondary hyperparathyroidism with chronic renal failure because it significantly inhibits a rise in i-PTH under conditions that cause no large changes in serum calcium.

A Study on Hemodialysis Leukopenia Using Various Dialyzers

Hemodialysis leukopenia was studied using various dialyzers and membranes. We found that dialyzers with cellulosic membranes caused marked leukopenia, but in recently developed non cellulosic membranes, its occurrence was significantly less. Additionally, our results showed a newly developed cellulose acetate membrane to correlate well with the non cellulose membranes regarding leukopenia, in spite of it being a derivative of cellulose. The extent of white blood cell decrease seemed to correlate inversely with an increase in the ultrafiltration rate per membrane area of dialyzer. The relationship between leukopenia and hypoxemia was examined also. The results of this investigation are included, however, we feel that more research is necessary before any conclusions can be made.

Bio-intact parathyroid hormone and intact parathyroid hormone in hemodialysis patients with secondary hyperparathyroidism receiving intravenous calcitriol therapy.

Abstract:  Intact parathyroid hormone (iPTH) assay has been the most widely used for the diagnosis of secondary hyperparathyroidism and evaluation of vitamin D therapy. However, 1–84 PTH assay might be a better diagnostic tool since iPTH detects not only 1–84 PTH but also large C‐terminal fragments, which would antagonize PTH action. Therefore, we conducted a multicenter study to evaluate the clinical usefulness of a newly developed immunochemiluminometric assay for 1–84 PTH, Bio‐Intact PTH (BiPTH). Thirty‐five uremic patients with secondary hyperparathyroidism participated in the study. Intravenous calcitriol therapy was continued for 12 months. iPTH and bone‐specific alkaline phosphatase (BAP) were monitored at each dialysis center to control the dose of calcitriol. Serum and plasma samples were collected from each center and both iPTH and BiPTH were measured using Allegro‐Lite assay reagents from Nichols Institute Diagnostics (San Clemente, CA, USA). Intravenous calcitriol suppressed iPTH after 1 month as well as BiPTH. Bone‐specific alkaline phosphatase decreased after 3 months. A high degree of correlation between Nichols iPTH and BiPTH (y = 0.3913 × + 19.517, r = 0.9561) was demonstrated with a BiPTH/iPTH ratio of approximately 0.44. Significant correlation between BAP and iPTH, or between BAP and BiPTH was not observed. Our limited data failed to demonstrate the superiority of BiPTH to iPTH. Therefore, further investigations would be  necessary to examine the relationship between BiPTH and bone histomorphometry.

Effect of 1,25-dihydroxyvitamin D3 on intestinal disaccharidases in uremic rats.

The effect of 1,25-dihydroxyvitamin D3 (1,25-D) on the activity of intestinal disaccharidases, maltase, sucrase, trehalase and lactase, was studied in five-sixths nephrectomized uremic rats. In uremic rats, maltase, sucrase and trehalase activities were lower than in sham-operated rats. Administration of 1,25-D produced significant improvement of maltase, sucrase, trehalase and lactase activities in uremic rats. These results suggest that activities of intestinal disaccharidases are reduced in uremic rats and these activities are normalized after 1,25-D administration.

Circadian rhythms of intestinal disaccharidases in experimental uremia in rats.

The activity of intestinal disaccharidases, maltase trehalase, sucrase and lactase, was measured in five-sixths-nephrectomized uremic rats fed ad libitum and kept under conventional lighting condition

A case of colon rupture due to dialysis amyloidosis.

β2 microglobulin (β2-MG) 由来の透析アミロイドーシスを合併した結腸破裂による腹膜炎の1症例を報告した. 症例は71歳, 女性, 透析歴は約15年, 急性腹症にて入院. 結腸破裂による汎腹膜炎と診断, 150cmの結腸を切除した. 腸管粘膜下層血管壁および筋層に, 免疫組織化学的にβ2-MG由来と同定されたアミロイド沈着を認めた. この筋層の広範囲の透析アミロイド沈着が結腸破裂の原因と考えられた.長期透析患者の腹部手術では腸管のアミロイド沈着を常に考慮すべきであろう.

Two hemodialysis patients with amyloid casts of .BETA.2-microglobulin origin.

摘出した腎の尿細管にβ2-microglobulin (β2-MG) に由来するアミロイド円柱ともいうべき所見を有する2症例を経験した. 第1例は15歳, 女性, 多発性嚢胞腎由来の慢性腎不全で透析歴4か月であった. 生体腎移植のため左嚢胞腎を摘出した. 左腎の残存皮質内の尿細管にアミロイド円柱を認め免疫組織化学的検査でβ2-MGと同定された. 第2例は71歳, 女性, 糸球体腎炎由来の慢性腎不全で透析歴8年であった. Grawitz腫瘍摘出時の残存尿細管にアミロイド円柱を認めた. いずれの腎にも血管壁に同時にアミロイド沈着がみられた. 透析アミロイド沈着は骨, 滑膜などの組織内, 心, 肺, 腎などの血管壁や心筋の組織にみられるが, 尿細管内に円柱状にみられることは少なく, β2-MGがアミロイド線維化する過程を考える上で重要な所見と考えられ考察をまじえて報告した.

Studies on amyloid deposition in the parathyroid glands of long-term dialysis patients.

長期透析患者で副甲状腺摘除を受けた50例の副甲状腺について検索し, 50例中47例において副甲状腺組織にアミロイド沈着を認めた. この47例中9例は手根管症候群の手術を受けており手根部横靱帯にアミロイド沈着が認められた. 副甲状腺の組織学的検索では, 被膜および結節間の隔壁, 小血管壁にアミロイド沈着が認められた.最近このアミロイドーシスの主要構成蛋白がβ2-microglobulin (β2-MG) であることが確認されている. 本研究でもこのアミロイドは過マンガン酸カリウム処置に抵抗性であり (非AA蛋白), 免疫組織化学的検査 (peroxidase-antiperoxidase法, immunofluorescence法) で抗ヒトβ2-MG抗体と反応した. これらの成績は透析アミロイドーシスは全身的に生じ得るし, 種々の臓器にアミロイド沈着が生じている可能性を示唆している.

Evaluation of overhydration in diabetic patients at the beginning of regular dialysis treatment.

糖尿病性腎症由来の腎不全患者においては, 慢性腎炎由来の腎不全患者よりも, 慢性透析導入時に溢水状態にある患者の多いことが知られている. これらの溢水状態にある糖尿病性腎症患者の, 慢性透析導入時の病態と治療成績を検討した. 本院において慢性透析に導入した糖尿病性腎症患者69例 (男40例, 女29例, 平均年齢59歳, 平均糖尿病罹病期間16年) を, 導入時点において溢水を伴う症例と溢水を伴わない症例に分け検討した. 溢水症例としては肺水腫23例, 心胸比の拡大24例, 胸水貯留13例, 腹水貯留14例, 心嚢液貯留7例を認めた. これらのいずれかを有する症例33例を溢水症例とした.溢水症例は非溢水症例よりも導入時のクレアチニン, 血中総蛋白, 酸素分圧が低値であり, 1日尿蛋白の排泄量が高値であった. 一方, 性, 年齢, 糖尿病罹病期間, インスリン使用に関しては両群間に差はみられなかった. 導入3か月目までの死亡は6例にみられ, 全例溢水症例であった. 死因は, 心不全2例, 感染症2例, 脳出血, 消化管出血各1例であった. 溢水症例においては, 直接穿刺による緊急透析例が多く, 導入後10日間における透析回数, 透析時間, 総除水量が多かった. 溢水状態にある症例に対してはより早期の導入を心がけた, 1984年以後の症例の導入期死亡例は23例中3例と, それ以前の10例中3例より若干減少した.以上, 溢水状態にある糖尿病性腎不全患者は, 温水のない症例よりも導入時死亡の頻度が高く, より早期に透析療法に導入し, 溢水の是正をはかる必要があると考えられた.

An autopsy case of a diabetic chronic renal failure patient demonstrating amyloid deposition containing .BETA.2-microglobulin in the islets of Langerhans.

糖尿病性腎不全で4回の血液透析後に消化管出血で死亡, 剖検により膵ラ氏島にβ2-MG由来のアミロイド沈着を認めた症例を報告する. 68歳, 女性, 約10年前初めて糖尿病と診断され食事療法を行っていた. 約2年前よりインスリン療法開始, 蛋白尿出現. 4か月前より高窒素血症, 浮腫のため入院, 保存的治療を行っていたが高窒素血症増悪のため血液透析を開始, 計4回の透析を行うも消化管出血で死亡. 剖検膵のラ氏島にアミロイド沈着がみられ, PAP法による免疫組織化学検査でアミロイド蛋白はβ2-MGを含むことが証明出来た. 他の全身臓器にはアミロイド沈着はみられなかった. 長期透析症例の全身臓器のアミロイド沈着の報告はあるが, 短期の糖尿病性腎不全の膵ラ氏島にβ2-MG由来のアミロイド沈着がみられたのは稀で珍しく貴重な症例と考えられた.