Total body water was measured by means of dilution technic with 99.8% deuterium oxide administration in normal subjects (controls), nephrotic (NS) patients with or without edema, and in longterm hemodialysis (HD) patients. Lean body mass (LBM) was calculated from height, body weight, and waist girth. Body fluid was evaluated according to the TBW/LBM ratio in HD patients. Effect of volume of body fluid on blood pressure was also investigated. Relationship among cardio-thoracic ratio (CTR), standard body weight (SW), and TBW were examined. SWTBw calculated from TBW and LBM, and. SW_CTR estimated mainly from CTR, blood pressure, were compared. The total body water to body weight ratios (TBW/BW) in controls, NS, and HD patients were 61.2±1.2%, 71.3±3.7%(with edema), 60.9±6.4% (without edema), 64.5±6.9% (pre-HD), 62.6±6.6% (post-HD) respectively. The mean TBW/BW of NS patients with edema was significantly greater than those of controls, NS patients without edema, and post-HD patients. The TBM/LBM value above 0.78 was suggestive of overhydrated state in HD patients. The mean TBW/LBM in HD patients was 0.757, which was greater than that of controls. Hypotension during HD was seemingly induced by excess ultrafiltration regardless of the value of TBW/LBM. No relationship among CTR, SW, and TBW was observed in HD patients, but the mean TBW/LBM of patients with the CTR exceeding 55% was 0.786, which suggested as overhydrated state. It is useful to determine TBW/BW and TBW/LBM in order to evaluate of volume changes in body fluid of longterm HD patients.

抄録全体を表示

Ischemic insult has been considered a cause of cellular injuries under certain circumstance, such as the disturbance of energy metabolism, the alternation of calcium homeostasis, the production of oxygen radical and the release of lysosomal protease. The present study was designed to clarify the pathophysiological effects of coenzyme Q10 (CoQ10), diltiazem, superoxide dismutase (SOD) and urinastatin on the development and progression of ischemic acute renal failure (IARF) of the rat. At 24 hours after reflow following 45 minutes ischemia, serum urea nitrogen, creatinine and fractional excretion of sodium were 99.3 mg/dl, 3.14 mg/dl, 5.95% respectively, in non-treated IARF rats. Renal ATP content was reduced to 0.91 μg/mg. prot. from 10.59 μg/mg. prot. at 10 minutes after ischemic insult, and remained at almost the same level throughout the entire 45 minutes ischemia. Although the subsequent blood reflow resulted in the recovery of ATP content, it was up to 50% of normal level at 24 hours after reflow following 45 minutes ischemia. During the ischemic period, the pathological changes were mild, whereas, after reflow, tissue involvement was mainly localized in the S3 segment of the proximal tubule. Major alteration were the loss of brush border, high amplitude swelling of mitochondria with matrical densities and fragmentation of the epithelial cell. At 24 hours after reflow, it was observed that renal function was superior in IARF rats treated with CoQ10, diltiazem, SOD and urinastatin. The treated rats also had higher ATP contents and showed less pathological changes than non-treated rats. Among these inhibitory agents, diltiazem exerted the most reliable effect. From these results, it was concluded that IARF was obviously caused by such pathophysiological mechanisms as mentioned above. Especially, Ca influx into the cells is one of the most important factors on pathogenesis of IARF.

抄録全体を表示

A 59-year-old woman was admitted to the hospital with a complaint of right visual disturbance. At admission, she had proteinuria and microscopic hematuria. The pulmonary X-ray showed bilateral hilar lymphadenopathy (BHL) but tuberculin test were negative. Also, bronchoalveolar lavage (BAL) and renal biopsy were performed. Bronchoalveolar lavage fluid (BALF) contained a high percentage of OKT 4 positive cells. In renal biopsy, light microscopic study showed thickening glomerular basement membrane (GBM) with tubulo-interstitial legion. Immuno-fluorescent study revealed granular deposits of IgG along glomerular capillary wall. Electron micro-scopic study showed subepithelial electron dense deposits of GBM, which are characteristic for membranous nephropathy (MN). It is well known that both sarcoidosis and MN are associated with immunological abnormality. This case might be significant for the study of pathogenesis of sarcoidosis.

抄録全体を表示

We designed experiments to reveal the effects of a S₂ serotonergic receptor antagonist, ketanserin, on the vascular eicosanoid system and the relevance to medial hyperplasia in spontaneously hypertensive rats (SHR). 2-week ketanserin treatment (5mg/kg/day) significantly decreased systolic blood pressure by 7% when compared to untreated SHR. The blood pressure reduction was associated with a significant decrease in vascular thromboxane A₂ (TXA₂) generation and sustained prostacyclin (PGI₂) production, thereby shifting PGI₂/ TXA₂ ratio toward vasodilatation, In contrast, the trichlormethiazide treatment, which achieved blood pressure reduction to almost the same extent, significantly decreased PGI₂/TXA₂ ratio. Vasodilator eicosanoids, e. g. PGI₂, PGE₂ and PGD₂, dose-dependently decreased (³H) -thymidine uptake by vascular smooth muscle cells in culture whereas vasoconstrictor TXA₂ enhanced (³H)thymidine uptake in a dose dependent manner. Indeed, 2x10^-5 M ketanserin significantly decreased (³H)thymidine uptake by vascular smooth muscle cells by 48% although the same dose of methysergide, nonspecific serotonin inhibitor, did not affect the uptake by vascular smooth muscle cells. These results clearly indicate that the blood pressure reduction in ketanserin treatment is uniquely associated with a decrease in vascular thromboxane generation, and that it is possibly beneficial to protect vascular wall against medial hyperplasia of vascular smooth muscle cells, an integral component of arterial sclerotic changes in hypertension.

抄録全体を表示

A radioimmnoassey was performed for direct measurement of urinary active and trypsin-activatable inactive kallikreins excretion in 34 patients with Type II diabetes mellitus. (1) Diabetics showed slightly low total (inactive plus active) kallikrein excretion, normal inactive kallikrein excretion and significantly low active kallikrein excretion and active-to-total kallikrein ratio. (2) Total kallikrein excretion was normal in normotensive diabetics and hypertensive diabetics without nephropathy, low in hypertensive diabetics with nephropathy. Active kallikrein excretion and active-to-total kallikrein ratio in hypertensive diabetics were remarkably low regardless of nephropathy. (3) Para amino hippurate clearance correlated with total kallikrein excretion in normal subjects and, with active kallikrein excretion and active-to-total kallikrein ratio in both normal subjects and diabetics, but not with total kallikrein excretion in diabetics. Creatinine clearance did not correlate with total, inactive kallikrein excretions and active-to-total kallikrein ratio. (4) A positive correlation was found between fractional sodium excretion and active kallikrein excretion in normal subjects, but not in diabetics. The results suggest that reduction in ratio of active-to-total kallikrein by renal dysfunction might decrease sodium excretion in diabetics with nephropathy.

抄録全体を表示

Twenty patients with renovascular hypertension were followed for at least 1 year (mean 3.3 years) after successful percutaneous transluminal angioplasty (PTA). Renal arteries were patent in 13 (65%) patients and were re-stenosed in 7 (35%). In 12 patients with unilaterally stenosed renal artery which were patent at the end of the follow up period, 6 patients were normotensive, the other 6 patients had less degree of hypertension. Determinations of renal vein renin were only of limited prognostic value. Renal blood flow pattern by doppler echography improved after PTA in the 12 patients Radioisotope renogram showed tendency of improved Tmax ratio (stenotic kidney/nonstenotic kidney) from 1.5±0.8 to 1.0±0.2 (mean±SD, p<0.1) Serum creatinine levels decreased significantly from 1.2±0.5 mg/dl to 1.0±0.2 mg/dl (p<0.05) and creatinine clearance increased from 72.1±18.5 ml/min to 99.6±31.7 ml/min (p<0.02). The size of the stenosed kindneys increased from 11.2±0.7 cm to 12.0±0.8cm (p<0.01), while the size of the contralateral kidneys did not change. These results indicate that PTA has favorable long-term effects on blood pressure and renal function with restoration of renal size in cases with patent renal arteries after this procedure.

抄録全体を表示

In order to study the characteritics of oxlate transport across the brush border membrane, we studied oxalate uptake and efflux by rat renal cortical brush border membrane vesicles (BBMV). The vesicles were prepared with MgCl₂ precipitation method and oxalate uptake was measured by a modification of the rapid millipore filtration technique, In order to analyze efflux of oxalate from BBMV, the vesicles were pre-equilibrated with 100 μM [14-C]-oxalate for 10 min, at 30°C. Themperature dependent and independent oxalate uptake were observed under the conditions of salt and anion free medium. Temperature dependent oxalate accumulation showed "over shoot", indicating carrier mediated oxalate flux. The stimulating effect of an inside alkaline pH gradient on oxalate uptake failed to show at intravesicular pH 8.5. The efflux of oxalate from pre-loaded BBMV showed three steps decreasing curve, Initial rapid efflux was inhibited by extravesicular 5 mM para-aminohippurate (PAH) and low temperature (5°C). Extravesicular 100μM PAH had no effect on oxalate efflux. These data suggested a carrier mediated oxalate transport system across the barrier from intracellular to luminal site. An outwardly directed chloride (Cl) gradient stimulated oxalate uptake in BBMV. RIDS, anion exchange inhibitor, inhibited this Cl-stimulated oxalate uptake completely. Harmaline, a Na-coupled cotransport inhibitor, had no effect and Probenecid, an organic anion transport inhibitor, caused 45% inhibitory effect on Cl-gradient stimulated oxalate transport system via anion exchange in the rat kidney BBMV.

抄録全体を表示

In an attempt to clarify the influence of pregnancy on the natural course of IgA nephropathy, the courses of 79 pregnancies occurring in 47 patients with the disease were studied. These resulted in 3 artificial and 10 spontaneous abortions, and two pre-term and 64 fullterm deliveries. Fifty four maternity passbooks were analyzed. In 22 pregnancies (40.7%) proteinuria was increased during the third trimester, and in 13 (76.5%) of 17 pregnancies receiving postpartum urinalysis, urinary protein was decreased to the level of the first trimester within one month after delivery. In two of the remaining four patients with a persistent increase in proteinuria, renal biopsy was carried out two months after delivery, revealing focal glomerular sclerotic lesions, in addition to mild mesangial proliferation compatible with IgA nephropathy. These findings indicated that increased urinary protein observed in the two pregnancies might be attributed to a complication of pre-eclamptic focal glomerular sclerosis rather than exacerbation of underlying IgA nephropathy. The glomerular filtration rate (GFR), examined in 27 patients both before and after pregnancy, was decreased in only two patients (7.4%), but these reductions appeared to go with the individual natural course. In 6 (15.0%) of 40 pregnancies, proteinuria was increased within one month after delivery, and one of them was diagnosed both clinically and pathologically as the acute exacerbation of IgA nephropathy. These data suggest that patients with IgA nephropathy might show transient acute exacerbation just after delivery rather than during pregnancy, and that even if such exacerbations occurred, pregnancy might have little influence on the natural course of the disease.

抄録全体を表示

Clinicopathological study on IgA nephritis was carried out in order to clarify the factors to promote the progression of the disease. Total 118 cases of IgA nephritis confirmed with renal histology of the biopsied tissue were followed up in our kidney center at least two years following the biopsy. As a result, histological changes tended to be more severe in elder group at the time of biopsy and longer history of the disease. Renal function tended to be decreased in the cases with more proteinuria. Nephrotic syndrome seems to be one of the pocesses in which the disease is exacerbated. In addition, 21 cases with rather progressive courses following the biopsy revealed poor control of blood pressure, frequent upper respiratory infection, and more physical activities on their lives, which appear to be the risk factors. Clinical symptomes such as hematuria and proteinuria and histological changes were significantly more severe in the cases with IgA depositions spreading into the glomerular basement membrane, as compared to the ordinary cases with IgA depositions, limited in the mesangium. These results suggested that IgA depositions in glomerular basement membrane might be also one of the poor prognostic factors.

抄録全体を表示

Incubation of normal human serum with hemodialysis membranes in vitro resulted in conversion of C3 which was detected by crossed immunoelectrophoresism In addition, formation of C3d was also observed, as was detected by double-decker rocket immunoelectrophoresis, Furthermore, breakdown products of complement (iC3b, C4d & Bb) in plasmaa samples were measured by ELISA, The microassay plates were coated with monoclonal antibodies which bind specifically to human iC3b, C4d and Bb, respectively, while the plasma samples were drawn from five polycystic kidney patients during initial hemodialysis. As a result, the iC3b and Bb levels in plasma were seen to increase during hemodialysis but the C4d levels revealed no significant changes. It was also observed that the Bb levels in patients undergoing hemodialysis were significantly higher than those in various renal and collagen diseases. Terminal complement complex (TCC) was not present in detectable amounts in normal human serum when measured by ELISA. However, incubation of normal human serum with hemodialysis membranes in vitro resulted in detection of TCC. TCC was present in the same plasma samples drawned from the five polycystic kidney patients during initial hemodialysis. It is suggestive that activation of complement by hemodialysis membrane is predominantly mediated through the alternative pathway and products such as TCC and anaphylatoxin are formed by this activation.

抄録全体を表示

Deferoxamine (DFO) has been widely used in the treatment of aluminum toxicity in patients on chronic dialysis. Mucormycosis is an opportunistic infection caused by fungi of the Mucorales order and some reports suggested a role for DFO in the precipitation of this infection A 50-year-old man had been on hemodialysis for 16 years. 6 weeks before admission, he was begun on DFO because of aluminum toxicity. 2 weeks before admission, general fatigue and fever developed and followed by headache and loss of vision. He was admitted to this hospital with disturbed consciousness. His clinical course and a CT scan of the head suggested cerebral infarction. Within 24 hours he required ventilatory support and died 5 days after the admission. On autopsy, rhino-cerebral mucormycosis was demonstrated with a mycotic thrombus involving the left middle cerebral artery. Dialysis-related mucormycosis has recently appeared in the literature. We feel that hemodialysis patients on DFO may be at risk for potentially fatal mucormycosis infections. With a possible relationship between DFO treatment and this fatal opportunistic infection, caution should be given before using this drug and the indications should be definitive.

抄録全体を表示

The toxicity of uremic fluorescent substances (F-ure) in hemofiltrates of a dialysis patient on the respiration of rat liber mitochondria was studied in comparison with some fluorescent substances (F-cir) in a cirrhosis urine. These substances found in both the body fluid of chronic disease were fractionated by hydrophobic HPLC. And the characteristic of (1) F-ure and (2) F-cir was as follows: the hydrophobicity based on Sasagawa's constant, (1) 1.1-1.3 & (2) 1.8; λ max in UV spectrum, (1) 231, 356 nm & (2) 220-230, 290 nm; Em in fluorescence, (1) 461 nm & (2) 361 or 504-7 nm. When F-ure was added into mitochondrial respiratory medium, the respiration of succinate (State 4) decreased about a half in the presence of phosphate and succinate/ADP respiration (State 3) was much suppressed. And about a quarter of this suppression was released by an uncoupler (SF-6847), whereas F-cir on the state 3 respiration showed to be stimulative effect in like manner of uncoupler. The toxicity of uremic fluorescent substances on cellular energy generation could be demonstrated by decreased respiration of mitochondria.

抄録全体を表示

Immunofluorescence and immunoperoxidase staining were carried out to determine the correlations between the progression of glomerular sclerosis and changes in the amount and distribution of glomerular extracellular components, such as Type I, III, IV, V, VI collagen, laminin (LN) and fibronectin (FN) in patients with various types of glomerulonephritis and diabetic nephropathy. Six patients with IgA nephropathy, four patients with membranoproliferative glomerulonephritis, four patients with rapidly progressive glomerulonephritis and six patients with diabetic nephropathy were examined. The intensity and distribution of Type IV collagen, LN and FN were similar between the glomeruli from normal individuals and patients with mild stages of glomerulonephritis and diabetic nephropathy. However, staining of Type I, III or V collagen was not observed in the glomeruli from normal individuals and such patients. In more advanced stages of glomerulonephritis and diabetic nephropathy, the amounts of Types IV and VI collagen, LN and FN were increased markedly in the mesangium, and their distribution extended along the glomerular capillary walls. The intensity of Type IV collagen, LN or FN in the nodular sclerotic lesions of glomeruli was decreased significantly in patients with glomerulonephritis and diabetic nephropathy. On the other hand, staining of Types I, III and V collagen was observed focally in the sclerotic or hyalinotic glomeruli and around such glomeruli in these patients. In light microscopic examinations, the patients who had marked staining of Type I, III or V collagen by immunofluorescence showed severe damage of the basement membrane in Bowman's capsules. It is concluded that hyperproduction and/or infiltration of interstitial collagens, i.e. Types I, III and V collagen, is closely linked to the progression of glomerular sclerosis and hyalinosis in patients with various types of glomerulonephritis and diabetic nephropathy.

抄録全体を表示