To clarify the pathogenesis of focal glomerular sclerosis (FGS), aminonucleoside (AN) induced animal model of rat FGS was studied through two kinds of experimental procedures. In experiment I, AN (0.5mg per 100g body weight) was daily administrated subcutaneously to rats for 30 days. Furthermore, periodic unilateral nephrectomy and successive sacrifice of each animal was done from the 4 th to 88 th experimental day. Conventional light microscopic (LM) and immu nofluorescent (IF) studies for rat IgG, IgM and C3 of kidneys were done. Although full blown FGS picture was first seen in the rat kidney sacrificed in the 69 th day, earlier cases also revealed light microscopically considerable expansion and PAS positive deposits of the mesangial areas. IF studies showed rat IgG, IgM and C3 depositions predominantly in the mesangial areas, furthermore, intensity of their staining was gradually increased in the later obtained kidneys. It seemed that the depositions of these serum protein components always preceded to the occurrence of the segmental sclerosis of capillary tufts. In experiment II, besides 30 days daily AN administration, aggregated human γ-globulin (AH γ-gl) was injected to groups of rats at the 40 th, 60 th, 80 th and 100 th experimental day. Each group, consisting of 3 to 4 rats, was sacrificed periodically up to 5 days. IF study for human IgG was done besides conventional LM and IF studies. In results, the tendency of increased uptake and delayed disappearance of AH γ-gl in the mesangial areas was noted in AN administrated rats of later sacri ficed groups. Otherwise, the LM and IF studies were just in accordance with those of experiment I. From the hitherto described evidences, it was concluded that increased local accumulation of auto-logous serum protein components in the mesangial areas due to dysfunction of mesangial transport observed in nephrotic rat kidney may be important factor to produce focal sclerosis of capillary tufts leading to FGS through local ischemia and fibrosis.

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The role of coagulation-fibrinolysis system in the pathogenesis of Masugi nephritis in the rabbit was studied clinicopathologically. Effects of Urokinase administration on the progression of the glome-rular lesions were also studied. Following results were obtained. 1. Intraglomerular and extraglomerular fibrin deposition that has been considered to be an essential factor in the development of crescentic and disorganizing glomerulonephritis decreased imm-unohistochemically by urokinase treatment. 2. Urokinase treatment represented a suppression of an increase in BUN values and a suppression of a decrease in urinary fibrinolytic activity. 3. After the administration of urokinase fibrin-fibrinogen degradation products were found in the urine of most rabbits. The urinary FDP was thought to reflect predominantly lysis of intraglomerular fibrin deposits by urokinase. 4. Light microscopy showed the prevention of the glomerular accumulation of fibrin, crescent formation and progressive glomerular disorganization by urokinase treatment. Electron microscopy also showed a decrease in fibrin or fibrinoid deposits in Bowman's space by urokinase treatment. These results indicated that urokinase had suppressive effect on the development of Masugi glomerulonephritis in rabbits.

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The significance of the hyaline arteriolosclerosis in 85 cases of Focal glomerulosclerosis (FGS) which were diagnosed in Pathological Institute of Tuebingen University was studied semiquantitatively by using the index of arteriolosclerosis (Baler and Meyer, 1977). Comparative study of two groups, 27 cases of FGS with nephrotic syndrome (NS) in the third decade (20-30y) and 26 cases of minimal change lesion (MC) with NS in the same decade resulted as follows; 1. The hyaline arteriolosclerosis is rare in MC of the third decade. 2. This change is the significant pathological finding in FGS of the third decade. 3. No significant difference was found between FGS-hypertensive group and FGSnnonehyoertensive group. 4. Significant positive correlation between the severity of the glomerular changes and the severity of the vascular changes was found in FGS. The vascular change was not regarded as one of the primary changes in FGS. The vascular changes in FGS of each decades were examined and the following results were obtained; 1. Vascular change is a rare lesion in FGS of children 2. The significant difference of severity in vascular lesions was found between adults and children. 3. Significant positive correlation was found between the index of arteriolosclerosis in FGS and aging. From these results, the vascular change is regarded as an aging phenomenon that is accentuated by unknown factors in FGS.

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In order to investigate the role of local fibrinolytic activity of the kidney in the pathogenesis of glomerulonephritis and to clarify the basis of fibrinolytic therapy in the renal disease, cortical tissue plasminogen activator was examined by histochemical method in 111 cases with renal disease. Materials examined in renal disease included glomerulonephritis, nephrotic syndrome, systemic disease, etc. Relationship between tissue plasminogen activator and several parameters in coagulation-fibrinolysis system were also studied. The results obtained were as follows: 1. Higher f ibrinolytic activity was observed around cortical vessels and cortico-medullary junction. Lower activity was found around glomeruli. No fibrinolytic activity was found over cortical tubules. 2. Stronger fibrinolytic activity was observed in advanced glomerulonephritis than mild prolifenative glomerulonephritis and benign recurrent hematuria. Normal kidney and focal glomerulonephritis demonstrated weaker fibrinolytic activity than other glomerulonephritis. "Hemp-dialysis kidney" showedd the strongest fibrinolytic activity. 3. In the nephrotic syndrome, proliferativc change group and M. P. G. N. demonstrated stronger fibrinolytic activity than minimal change and membranous nephropathy. Cases with intra-glomerular fibrin deposit showed higher fibrinolytic activity than cases without it. 4. S. L. E, with nephrotic syndrome demonstrated stronger plasminogen activator than S. L. E without it. D. M nephropathy and E. P. H gestosis showed reduced plasminogen activator. 5. These results suggest that tissue plasminogen activator will increase in the glomerular proliferative lesion to remove the intra-glomerular fibrin deposit and play a role to reduce the glomerular injury. Thus, when plasminogen activator is in the process of consumption, glomerular injury willl progress by immunological mechanism and intra-glomerular coagulation. 6. In the treatment of renal disease, fibrinolytic therapy will be available for casee with persistent high plasminogen activator and declined tissue plasminogen activator. In practice, advanced glomerulonephritis, nephrotic syndrome with proliferative lesion, M. P. G. N and E. P. H gestosis will be a good indication for fibrinolytic therapy.

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There is no def snit criterion to treat bilateral renovascular hypertension at present. Although the effectiveness of angiotensin converting enzyme inhibitor (captopril) on unilateral renovascular hypertension is reported by several investigators, this is not always true about a patient with bilateral renovascular hypertension. A 21-year-old female with hypertension (160/110 mmHg) who had abdominal bruit and high plasma renin activity (4 ng/ml/h, normal range; 0.5-2.1 ng/ml/h) failed to respond to antihypertensives (diuretics or methyldopa). Although RI-renogram showed no difference in both kidneys, rapid sequence intravenous pyelogram revealed paradoxical hyperconcentration and ureteral notching on the left side. It was not until aortography was performed that we found severe stenotic changes in both renal arteries. In the split renal vein renin assays, the left side had higher renin activity (the left to right ratio was 1.6). A patch graft was applied to the left renal artery. After the operation, the blood pressure did not fall. A significant reduction of the blood pressure, however, was observed by the infusion of angiotensin analogue (sar¹-ile⁸-angiotensin II) in a sodium depleted state, while the blood pressure was rather elevated despite the administration of the same amount of the analogue before the operation. Oral administration of 100 mg of captopril which had no effect on the blood pressure before the operation, showed a reduction of mean blood pressure by 39 mmHg after the operation. Plasma renin activity was elevated transiently after the operation. Two months after the operation, the blood pressure was lowered to 130/80 mmHg with 75 mg/day of captopril.

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The effects of metoclopramide (MP), a dopaminergic inhibitor, on aldosterone (PAC), prolactin (PRL), cortisol (PF) and renin activity (PRA) in plasma and serum potassium (sK) and sodium (sNa) were evaluated in normal human subjects treated with dexamethasone (2 mg daily for 2 days). MP increased PAC from a baseline of 9.7±3.3 (mean±s. e.) to 12.7±4.4, 16.6±6.3, 17.1±5.9 (p<0.05), 15.7±5.7, 14.6±5.0 and 12.0±3.8 ng/dl at 5, 15, 30, 60, 90 and 120 min after MP administration, respectively. PRL was also increased by MP administration from a baseline of 4.8±2.5 to 35.0±3.4 (p<0.001), markedly to 84.3±9.4 (p<0.001), 80.5±5.5 (p<0.001), 70.0±5.5 (p<001) and 63.8±4.8 (p<0.001) ng/ml at 5, 15, 30, 60, 90 and 120 min after MP, respectively. On the other hand, PF, which was markedly lowered from a control of 6.3±2.5 to 0.34±0.11 (p<0.001) μg/dl with dexamethasone administration, did not change with MP infusion. Both sK and sNa did not change with MP administration. There was no significant correlation between changes in PAC and PRA at each time after MP administration. Also there was no significant correlation between changes in PAC and in PRL at each time after MP administration. These results suggest that MP increases plasma aldosterone independently of renal and pituitary mediations in normal man.

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The role of calcium-regulating hormones on the development of ROD in chronic hemodialysis patients was examined. On 48 uremic patients with or without ROD (P-ROD or P-0), the concentration of parathormone (PTH), calcitonin (CT) and 25-hydroxy-cholecalcif erol (25-OH-D₃) in plasma, as well as the other factors were determined. The following results were obtained: 1) The concentrations of PTH and CT in plasma and Ca⁺⁺ in whole blood on P-ROD were heigher than the corresponding values on P-0. The plasma 25-OH-D3 concentrations in both patients groups were lower than that in normal subjects 2) No significant ocrrelations among each measured concentration of these calcium-regulating hormones (PTH, CT and 25-OH-D₃) were found. 3) By hemodialysis, the plasma PTH concentration on P-0 markedly decreased, but in P-ROD, no change was observed. The plasma 25-OH-D₃ concentration and the CT concentration increased significantly in both patients groups 4) In the patients treated with 1α-D₃, plasma PTH concentration decreased, but the treatment with D₂ was ineffective 5) By rapid calcium infusion, there was a decrease in plasma PTH concentration and an increase in plasma CT concentration in P-0, while the both concentrations remained the same in P-ROD. These results suggest that the patients on chronic hemodialysis suffer from secondary hyperpa-rathyroidism, especially that P-ROD suffer from tertiary hyperparathyroidism.

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Serum and urinary β₂-microglobulin (β₂m) were measured by radioimmunoassay in 35 hemodialyzed patients and 22 control subjects (13 chronic glomerulonephritis and 9 healthy persons). 1) There was a significant correlation between serum β₂m (Sβ₂m) and creatinine clearance (Ccr) in hemodialyzed patients (r=-0.538) and in control subjects (r=-0.754) 2) Urinary excretion of β₂m (Uβ₂m) did not correlate to Ccr in hemodialyzed patients (r=0.174) but correlated in control subjects (r=-0.533). 3) In hemodialyzed patients an increased urinary excretion of β₂m per nephron (Uβ₂m⋅V/GFR) and an increase of glomerular filtration of β₂m per nephron (Sβ₂m⋅0.9⋅GFR/GFR) were found in comparison with control subjects. There was no correlation between urinary excretion of β₂m per nephron and glomerular filtration of β₂m per nephron in hemodialyzed patients (r=0.262) but was significant correlation in control subjects (r=0.713). (V; volume of urine) 4) Tubular reabsorption rate of β₂m did not correlate to golmerular filtration of β₂m per nephron in hemodialyzed patients (r=0.083) but correlated in control subjects (r=0.632). 5) Tubular reabsorption rate of β₂m correlated to urinary excretion of β₂m per nephron in hemodialyzed patients (r=-0.807) and in control subjects (r=-0.828). These facts suggest that in hemodialyzed patients main contributing factors of an increased excre-tion of β₂m are an excess of tubular load of β₂m and a decrease of tubular reabsorption capacity of β₂m and in control subjects an increased excretion of β₂m is mainly caused by an excess of tubular load of β₂m.

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The purpose of this study is to evaluate the effects of plasma exchange (PEx) in patients with SLE and to compare two methods of PEx with conventional continuous flow centrifugation (CF) and double filtration plasmapheresis (DFPP). In the latter procedure, two membrane filters with different pore sizes are applied to separate selectively large molecular fraction of plasma protein. 10 series of PEx (4 of 10 on CF and other 6 on DFPP) were performed in 7 patients who have fulfilled the ARA criteria of SLE. Series of PEx consisted of 3 to 8 exchanges by CF or DFPP, and 5 % albumin solution was used for substitution. From clinical viewpoint, several acute symptoms were immediately improved following PEx with both methods except nephrotic syndrome in 4 cases. In 4 patients with rapidly deterioration of renal function, clinical improvement was observed immediately after PEx. With reference to laboratory findings, there were significant decreases in immune complexes (IC), various autoantibodies, immunoglobulins and serum total protein after PEx. As to these data, there were no significant differences between both methods except for the quantity of albumin per series required to substitute (CF 356±118 vs. DFPP 198±61gm). Just before PEx, IC were detected in 8 of 10 series and PEx showed some effects in 7 of these 8 series. No serious adverse reaction was observed in both methods except three episodes of transient fever. Conclusion are obtained as follows: 1) PEx is effective to reduce symptoms immediately, but not effective for nephrotic syndrome secondary to lupus nephritis, 2) better result is highly expectable if pre-PEx IC is positive, 3) the advantage of DFPP is to be able to reduce an amount of albumin solution for substitution.

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Iatrogenic bleeding tendencies due to procainamide (PA) were observed in two male hemodialysis patients. One was a 55 year old patient who had been receiving 250 mg/day of PA for about one month for his supraventricular premature beats. Another was a 26 year old patient who had been receiving 750 mg/day of PA for about one year for his paroxysmal supraventricular tachycardia. Their prothrombin time, partial thromboplastin time and fibrinogen were within normal ranges in all. Serum levels of PA and N-acetyl PA (NAPA), an active metabolite of PA, were 1.5 μg/ml and 16.8 μg/ml in the former and 5.5 μg/ml and 42.0 μg/ml in the latter, respectively. In both cases, NAPA was markedly accumulated in the serum when compared with PA. Their bleeding tendencies disappearedd after the withdrawal of PA. Their platelet functions assessed by platelet aggregability were moderately to severely impaired when compared with those of male hemodialysis patients not receiving PA. This abnormal platelet aggregability was markedly improved after the withdrawal of PA. With the administration of PA (750 mg/day) to another patient on chronic hemodialysis for five days, platelet aggregability was suppressed moderately and it took two weeks after its withdrawal to return back to its pre-value. PA suppressed in vitro platelet aggregability at a final concentration of 50 μg/ml and severely at 500 μg/ml. The effect of NAPA was almost the same as that of PA. These data suggest that PA induces bleeding tendencies through its action on platelet function. In hemodialysis patients, PA should be administered with caref ull monitoring of serum levels of PA and NAPA or platelet aggregability because a marked accumulation of NAPA is always possible.

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