Kosei Kurosawa

Anti-DNA Idiotypes Deposited in Renal Glomeruli of Patients With Lupus Nephritis

Idiotypes (Id) of human anti-DNA antibodies, designated as O-81 Id, were specifically detected on the immune deposits of renal glomeruli in 46% of patients with lupus nephritis. Id-binding to anti-Id antibodies was blocked by free O-81 Id and to some extent by free DNA. DNase or acid buffer treatment failed to reveal new Id determinants on the deposits. O-81 Id and NE-1 Id activity were also detected on the renal eluate-derived IgG, but not IgM from the autopsy cases with lupus nephritis. The incidences of O-81 Id were not associated with histological features in the glomeruli, but the distribution patterns were similar to those of IgG deposits. Our study also showed that 65% to 70% of patients with IgG deposits either in the subendothelium or in the subepithelial area of the glomerular basement membrane (GBM) showed positive tests for O-81 Id. It was also noted that most patients with massive proteinuria had O-81 Id in their glomeruli. It is concluded that O-81 Id deposits are relatively specific for active lupus nephritis and that immunofluorescence studies using anti-Id antibodies may be clinically useful for specifying the renal lesions of systemic lupus erythematosus (SLE).

Management of Advanced Nephrotic Disease in Diabetics: Short-term and Long-term Effects of Angiotensin Converting Enzyme (ACE)-Inhibitors and a New Trial Using Camostat Mesilate

Two studies of the management of nephrotic diabetics were performed. Captopril (37.5 mg/day, n=16), decreased urinary protein excretion from 9.6 ± 1.6 to 4.9 ± 1.0 g/day, P < 0.05 (M ± SEM) and significantly decreased total cholesterol. No significant adverse effect was observed. Camostat mesilate (600 mg/day, n=15) decreased urinary protein from 4.8 ± 0.6 to 2.9 ± 0.4 (P < 0.01). Elevated plasma fibrinogen level and noticeably enhanced urinary fibrin degradation product (FDP) excretion were also attenuated by this medication. No serious adverse effect was noted. These types of medication, particularly when combined, seemed promising for the treatment of nephrotic diabetics. The long-term effect of ACE-I was retrospectively analyzed in 56 azotemic diabetics, of whom almost all had noninsulin-dependent diabetes mellitus (NIDDM). The patients were divided into two groups (group A: treated with ACE-I, n=27; group B: without ACE-I, n=29). The inverse creatinine deteriorated by 0.023 per month in group B and by 0.012 in group A. Although the mean blood pressure was kept at a similar level, HBA1c differed significantly. In an additional study, ACE-I slowed the progression rate in 10 patients with nephrosclerosis. Taking these observations into consideration, it is suggested that ACE-I might slow the progression rate of advanced diabetic nephropathy.

Changes in Urinary Methylguanidine in Cases with End-Stage Renal Disease

Methylguanidine (MG), one of the most detrimental uremic toxins, is a product of creatinine oxidation. Although the amount of MG output depends on the concentration of creatinine, it is thought that the participation of active oxygen in the process of MG production markedly boosts its productivity1. In patients with end-stage renal disease (ESRD), the level of MG output may depend on the formation of active oxygen, since such patients have an increased amount of ceratinine which is a precursor of MG2–6. In fact, some patients who have more than 10 mg/dl of plasma creatinine (P-CR) respond well to conservative therapy and do not require hemodialysis treatment.

Clinical problems in hemodialysis treatment (HDT) in patients with renal amyloidosis

アミロイドーシスによる腎不全患者6例に血液透析を施行し, 種々の問題点を経験した. 対象は, (1) 46歳男 (2) 49歳女 (3) 48歳女 (4) 37歳女 (5) 69歳男 (6) 51歳女の計6例である. 全例ステロイド抵抗性のネフローゼ症候群を呈し, 入院時既に低血圧, 心電図異常, 肝機能異常等の他臓器合併症を示す例が多かった. 腎生検で全例アミロイドーシスと確定診断した. 1例は膀胱癌に併発した続発性アミロイドーシスで, 5例は原発性アミロイドーシスであった. 浮腫出現から血液透析開始までの期間は1年から2年3か月であった. また乏尿から心不全に至る過程が急速であるため, 血清クレアチニン値が著明には上昇していないにもかかわらず, 緊急透析を必要とした. 導入時の血清クレアチニン値は1例で8.4mg/dlであったが他は6.6mg/dl以下であった. 内シャント造設は不良で, 4例は外シャントによる導入となった. 1回の手術で内シャント造設に成功した2例もシャントの発達は悪かった. 透析中に肝障害, 心筋障害, 心伝導系障害, 消化器障害 (特に食思不振) 低血圧等の他臓器合併症があり, 患者の一般状態を悪化させ透析療法の効果を阻害した. 中でも維持透析中の最大の問題点は低血圧症であった. 透析中に血圧が低いまま経過する例が3例あった. 残りの例でも透析中の突然の血圧低下が他の腎不全患者よりしばしば見られた. また透析終了直前よりも返血後に血圧が低下する例が2例あり, 血圧調節機構の何らかの異常が考えられた. 6例中5例は死亡しており, 透析療法開始後の生存期間は10日から2年10か月に亘った. 死因はそれぞれ, 外シャント開放による自殺, 肝不全, 極度の食思不振による全身衰弱, アミロイドによる冠動脈閉塞が原因となった心筋梗塞, 心伝導系障害による急性心停止であった. 1例は生存中であるが, 低血圧で一般状態不良である. いずれにせよアミロイド腎症の透析療法にはさまざまな問題点があり, 更なる検討が必要であろう.