Takashi Furuyama

Sjögren's syndrome and renal tubular acidosis

Abstract Clinical studies were conducted in four cases of Sjogrens syndrome complicated by renal tubular acidosis (group I) and in ten cases of Sjogrens syndrome without this complication (group II). No differences between the two groups were noted in respect to the ages of the patients or the duration of the disease. Hyperglobulinemia and an increase in serum IgG were observed in three of the four cases in group I, but no difference was found in the degree of increase when comparing the two groups. No differences were observed between the two groups when compared using various serologic tests. Marked lymphocytic infiltration was noted in the biopsy specimens of the lacrimal and parotid glands. In the kidney biopsy specimens in three cases of group I lymphocytic infiltration interspersed with plasma cells was conspicuous in the interstitial tissues. No lymphocytic infiltration was noted in one case without hyperglobulinemia but a marked interstitial fibrosis was seen. No remarkable changes were seen in the renal biopsy tissue in four cases of group II. Accordingly hyperglobulinemia of itself does not appear to be the primary cause of renal tubular acidosis in Sjogrens syndrome. Renal changes appear to represent one of several systemic changes occurring in Sjogrens syndrome. Therefore renal tubular acidosis is probably an inherent result of the disease process responsible for the development of Sjogrens syndrome.

Passive hemagglutination and hemolysis tests for the detection of anti-DNA antibody.

Passive hemagglutination (PHA) and hemolysis (PHL) tests using chromium chloride-treated sheep red blood cells were developed to detect and measure the anti-DNA antibodies. Sonication of native DNA was found to prevent the incidence of non-specific agglutination. Sheep red cells were coated with double-stranded DNA (dsDNA) which had been sonicated and treated with nuclease S1 to digest the single-stranded regions in the DNA. The specificities for dsDNA-coated cells were checked by inhibition studies in PHA test and plaque assay. In clinical studies fairly close correlations were found between the antibodies to DNA and the activity of the disease in patients with systemic lupus erythematosus (SLE). Complement-fixing antibodies were detected in most of SLE patients with active lupus nephritis, but rarely in those in remission. Anticomplementary activity seemed to be negligible in PHL test. These tests are simple and may be useful to the diagnosis and the management of SLE.

Quantitation of C3 nephritic factor of alternative complement pathway by an enzyme-linked immunosorbent assay.

We have developed an enzyme-linked immunosorbent assay (ELISA) for the quantitation of C3 nephritic factor of the alternative pathway of complement (NeFA). Incubation of the NeFA-positive serum (patient KS serum) with normal human serum (NHS) in Mg-EGTA resulted in the formation of C3-B-IgG complex. No complex was formed in EDTA. At first this was detected as three types of complexes: C3-IgG, B-IgG and B-C3, by the combination of antibodies. The reaction mixture in Mg-EGTA was filtered through an ACA 22 column, from which the complexes were eluted in the same part as the first protein peak. When IgG purified from KS serum was incubated with NHS in Mg-EGTA, B-C3 complex increased in proportion to the dose of IgG. These results indicated that only one kind of complex consisting of IgG, C3 and B (IgG-C3-B) was generated by the addition of NeFA to NHS. Serum NeFA could be quantified as the titer of B-C3 complex formed after its incubation with NHS in Mg-EGTA. Using the ELISA method, NeFA was positive in five out of six patients with membranoproliferative glomerulonephritis (MPGN) type II and in only one of 17 with MPGN type I. Titers obtained by the new method were in good accordance with those by C3 conversion and C3bBb stabilization assays for NeFA, and the new method was more exact and simple than the conventional methods.

Renal histopathology of Laurence-Moon-Biedl syndrome: tubulointerstitial nephritis without specific glomerular changes.

Hiroshi Sato, MD, Second Department of Internal Medicine, Tohoku University School of Medicine, 1-1, Seiryo-cho, Sendai 980 (Japan) Dear Sir, Laurence-Moon-Biedl syndrome (LMBS) is known to be accompanied not infrequently by renal impairment. As to the renal histology of LMBS, conflicting results have been reported. Faulkner et al. [1] described subendo-thelial scalloping of the glomerular basement membrane (GBM) with swelling of the endothelial cells. Price et al. [2] documented marked ultrastructural alterations of the GBM composed of effacement of the trilaminar architecture, segmental irregular thickening, and accumulation of granular or fibrillar material within the inner third of the GBM. They suggested that these ultrastructural changes might be the primary glomerular abnormality in LMBS. On the contrary, Tieder et al. [3] reported four cases of LMBS in which tubulo-interstitial lesions were noted without specific ultrastructural changes in the GBM. Here we present a patient with typical LMBS. In this case, tubulo-interstitial and vascular lesions were the most remarkable abnormalities. Fig. 1. Light micrograph of the kidney demonstrating diffuse interstitial fibrosis, tubular atrophy, and severe sclerotic change of the arterioles. There were no proliferative changes in the glomeruli. HE, ×95.

Hemosiderosis secondary to parenteral iron therapy in chronic hemodialysis patients

目的: 慢性透析患者の貧血に対し鉄剤投与や輸血が行われる事が多い. この際の合併症であるヘモジデローシスは従来早期診断が困難であり, 血清鉄値, UIBC, 血清フェリチン値, 臨床経過等により総合的に推定されるのみであった. しかしCTの出現により, 鉄の肝臓への異常蓄積が早期にかつ直接的に診断できるようになった. このような観点から我々は鉄剤投与および輸血を受けた透析患者25名に肝CTを施行した.結果: 血清フェリチン値と鉄投与量の相関 (r=0.491, 0.01<p<0.02) に比べ, 肝CT値と鉄投与量の間には良い相関が得られた (r=0.714, p<0.001). もともと肝機能障害のある3例を除く22例中10例に一過性のトランスアミナーゼ値 (以下Tra.) の上昇がみられ, 残り12例は経過中Traは正常であった. Traの上昇のあった群はTraの正常な群に比べて有意に鉄投与量が多く, また有意に肝CT値が高かったので, 鉄剤投与の結果肝ヘモジデローシスがおきTraが上昇したものと考えられる. これに対し, 血清フェリチン値とTraの上昇の間には相関はみられなかった. また輸血によっても肝CT値は上昇する傾向がみられた. 肝CT値の上昇とともに脾CT値もわずかながら上昇した. 鉄剤投与を中止して6ヵ月後にCTを再検してみると, 肝CT値はほとんど変化せず, 鉄の肝臓への沈着は不可逆的である事が示唆された.以上の結果により, 肝CT値は血清フェリチン値よりも正確にヘモジデローシスを反映しており, その早期診断に有用と思われる. 鉄剤投与または輸血の施行されている透析患者には経過を追って肝CTを施行し, 止むを得ない場合でも肝CT値80 H. U. を越えないようにすべきである. ただし肝CTには鉄欠乏に関する情報はなく, 従来通り血清フェリチンも併せて参考にすべきであろう.

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.

Plasma renin activity in acute renal failure induced by norepinephrine infusion in unilaterally nephrectomized dogs.

Plasma renin activity was determined by bioassay prior to, during and following a 2-hour infusion of norepinephrine into the renal artery in unilaterally nephrectomized dogs in order to examine the role of renin-angiotensin system in norepinephrine-induced ARF. ARF was induced in 5 of 8 dogs receiving 0.75 microgram/kg/min of norepinephrine, but not in the remaining 3 dogs and 2 dogs infused with 0.6 and 0.4 microgram/kg/min of norepinephrine. There proved no difference in plasma renin activity in renal venous blood between the dogs with and without ARF when followed up to 2 h after the discontinuation of the infusion. The same results were obtained when the plasma renin activity in the foreleg vein was followed at 24, 48 and 72 h after the infusion. The renin-angiotensin system does not seem to contribute to the reduction of renal function in norepinephrine-induced ARF in dogs.