The present study aims to clarify natural history of mesangial proliferative glomerulonephritis (mes PGN) as one morphologic entity. A total of 190 patients, 115 males and 75 females, were studiedd in the First Department of Internal Medicine, Kanazawa University Hospital and the affiliated hospitals between 1961 and 1979. Their clinical course and GFR were followed for more than 2 years up 15.5 years, and 55 cases underwent the serial renal biopsies with intervals of up to 12.5 years. The glomerular changes were classified into the following six forms: 1) minimal to mild mes PGN (LGN; 87 cases), 2) LGN with focal and segmental lesions defined as segmental necrosis, sclerosis and/or small crescent in more than 20% of glomeruli observed (LGN+F; 20 cases), 3) moderate mes PGN (CGN; 34), 4) CGN+F (23), 5) marked mes PGN (adv. CGN; 16) and 6) adv. CGN+F (l0). 82% of patients with LGN kept normal GFR and 18% showed subnormal GFR at the end of the follow-up periods (60.8±4.3mos.), and no case progressed to renal failure. In contrast, one-third with LGN+F disclosed a decline of GFR, with 3 cases who fell into the azotemic level (the follow-up periods 59.3±7.1mos.). In CGN cases, 44% of them already had variably decreased GFR at the time of work-up, and 50% with initially normal GFR gradually lost the function during the observation penods (59.1±5.9mos.). This tendency of progression was more pronounced in CGN+F (the periods; 48.1±5.1). There was no difference in the clinical course between adv. CGN and adv. CGN+F, since all but one have succumbed to renal failure within 3 years. Serial biopsy studies supported these functional features. Especially the cases with LGN+F revealed frequent transition to more severe forms. Thus, the degree of mesangial involvement and the presence of focal and segmental lesions appeared to be important factors in determining the prognosis of mes PGN. Since a form of LGN+F is consistent with the so-called focal glomerulonephritis, the present results contrasts to the known consensus that the latterr follows a benign course. Further, any effects of immunosuppression and anticoagulation including anti-platelet agents recently introduced should be evaluated against the natural history of each form of mes PGN.

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We previously described that Masugi nephritis in nude (nu/nu) mice was characterized by thrombotic glomerular lesion associated with host IgG deposition similar to that in their normal littermates (nu/+). In this paper to clarify the nature of deposited antibody in nu/nu mice, an accerelated model of Masugi nephritis (preimmunization with heterologous gamma globulin) was used; host antibody deposition was seen only in nu/+ mice. It is concluded that antibody response to heterologous antiglomerular basement membrane antibody does not play a role in pathogenesis of nu/nu Masugi nephritis.

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The distribution of fibronectin in human renal glomeruli with a variety of pathologic disorders was studied on biopsy specimens by immunofluorescence method. The distribttion pattern was classified into two groups. One was the mesangial patternn in which fibsonectin fluorescence was restricted mainly to the mesangial area. Another was the capillary pattern in which the presence of the fluorescence along the capillary walls in an continus manner was found in addition to the presence in the mesangial area. The mesangial pattern was found in normal kidneys and in the majority of the cases without thickening of capillary walls or without deposits in the basement membrane. The capillary pattern was observed in the most of the cases associated with thickening of capillary walls or the deposits. Fibrin deposition was found in the group of the capillary pattern in a significantly higher frequency then that in the group of the mesangial pattern. Furthermore, fibrin deposition in the capillary pattern was seen mainly along the capillary walls. In these cases with fibrin deposition, the deposits of α₂-plasmin inhibitor and plasminogen, which are major components of the fibrinolytic system, were also seen along the capillary walls in high frequencies. There was a significant association of the capillary pattern with nephrotic syndrome. However, the frequency of the capillary pattern in the cases with nephrotic syndrome was not significantly high, suggesting the presence of additional factors causing the capillary pattern other than nephrotic syudrome.

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In order to clarify the role of platelets on immune complexes nephritis, we investigated that the behavior of platelets, that is, the immune release of chemical mediators, platelet-surface immunoglobmlins and platelet functions during acute serum sickness nephritis. The following results were obtained. The immune release of vasoactive amines, especially serotonin (5-HT) from platelets were existed at the time of immune elimination and before the appearances of proteinuria. Immunoglobulins were bound to the surface of platelets when the 5-HT release from platelets was occured. And the ability of platelet aggregation induced by addition of ADP was decreased at the same time. Nevertheless the survival rate of platelets was within normal range. The deposition of immune complexes to the kidney tissues was increased by the addition of chemical mediators from platelets. Further by the treatment of anti-platelet drug, dipyridamole undergoing acute serum sickness nephritis, the release of 5-HT from platelets, proteinuria and the deposition of immune compleyes were inhibited. We concluded that in acute serum sickness nephritis of rabbits, the immune release of vasoactive amines from platelets by means of binding to C3 receptors of rabbit platelets may play important roles on the deposition of immune complexes and pathogenesis of glomerulonephritis.

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Uremic patients on prolonged maintenance hemodialysis (HD patients) are at high risk for atherosclerotic cardiovascular complications and have an unique dyslipoproteinemia in high incidence. The purpose of the present study is to investigate apoprotein profiles which may play an important role in lipoprotein (Lp) metabolism, especially very low density Lp (VLDL) catabolism in HD patients with a dyslipoproteinemia. We studied apoprotein profiles in six HD patients with a typical dyslipoproteinemia as compared with four normal controls by polyacrylamide gel (PAG) disc Lp electrophoresis, ultracentrifugal analysis, apoprotein electrophoresis (Kane's method) and chemical methods. HD patients showed broad mid-band Lp pattern (BMP) on PAG disc Lp electrophoretogram and three abnormal low density Lp (LDL) subfractions (Sf 13-15, Sf 10, Sf 6-7) in LDL Schlieren profile of ultracentrifugal analysis, Apoprotein electrophoretogram showed a decrease in apo C-I, apo C-II and apo A-I, and an increase in apo C-III in VLDL and high density Lp (HDL) of HD patients as compared with normal controls. Arginine-rich peptide did not change in patients and controls. Apo C bands and arginine-rich peptide were detected in LDL subfractions of HD patients, but these bands were not detected in LDL of normal controls, because apo B in LDL could not be soluble in 1, 1, 3, 3-tetramethylurea (TIM) used in Kane's apoprotein electrophoresic method. The results of the present study suggested that the dyslipoproteinemia in HD patients might be induced as a part by defective VLDL catabolism due to a decrease of apo C-I and apo C-II as lipoprotein lipase (LPL) activator, and an increase of apo C-III as LPL inhibitor of VLDL catabolism.

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Out of 120 patients subjects to maintenance hemodialysis, there were selected 25 patients who suggested iron deficiency auemia, but neither had been subject to parenteral iron therapy nor blood transfusion, nor had any factors such as hepatic diseases and infections which influence the behavior of ferritin for the past 3 months before the study, and then iron was given parenterally to them. Red blood cell ferritin and serum ferritin were determined before and after the iron administration to study the relation between the obtained values and anemia. In the results serum ferritin was higher in the patients under hemodialysis than in normal ones, was increased significantly by iron administration, and kept the level for a long time. Red blood cell ferritin was also increased significantly by iron administration. In the relation with anemia, serum ferritin fluctuated so greatly that the correlations with the degree of anemia and its improvement were not so clearly observed, while red blood cell ferritin was significantly low in the anemia-improved group compared with that in the anemia-non-improved group; thus, the value can be used as a reliable guide to the iron therapy in hemodialysis patients.

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Thirty one patients, under maintenance hemodialysis 15 male and 16 female, aged from 19 to 62 years old, were studied with special referrence to biochemical parameters concerning renal osteodystrophy. Based upon duration of hemodiallysis, 31 patients were categorized in three groups as follows, 8 patients having duration less than 1 year, 8 pateints less than 2 years and 15 patients more than 2 years. Serum Al-P₃ activity not only well correlate with serum Al-P activity but also linealy arised with increasing of duration of hemodialysis, i.e., 2.6±1.4K-A in group less than 1 year, 5.7±5.3K-A in group less than 2 years and 9.4± 10.2K-A in group more than 2 years. Serum i-PTH value was elavated as high as 3.6±3.0ng/ml in all patients studied and high value was found in patient of longer hemodialysis duration, i.e., 2.5±2.3ng/ml in 16 patients less than 2 years and 4.8±2.6ng/ml in 15 patients more than 2 years. Decrease in serum Ca++ value was not remarkable in most patients, but many of those having somewhat lower value of serum Ca++ was likely to have higher level not only in serum Al-P₃ activity but also in serum i-PTH value, too. Concerning serum pyrophosphatase activity, we could find significant higher value of 9.0±3.8nmol/min/ml in patients compared to 5.6±0.8nmol/min/ml in control normal subjects (n=5). On the othere hand, we could not any difference in serum HP level in patients against normall subjects, i.e., 6.2±5.2mg/l in patients compared to 6.1±2.0mg/l in control normal subjects (n=5). As to correlationship among these biochemical index parameter, correlation between pyrophospatase and i-PTH (r=0.658 p<0.01). and between Al-P₃ and i-PTH (r=0.724 p<0.01), were noted in the sense of estimation responsibility of both osteoblast and osteoclast against PTH secretion.

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An Innovative, simultaneous hemof filtration and hemodialysis system was developed which has absolutely no need of the infusion fluid. The system employs two high-flux membrane dialyzers in a direct series, and causes the dialysate to flow in the direction opposite the blood flow. First, a dialysate flow equalizer was employed to control the dialysate flow at the inlet and outlet, and their difference was arranged to be the water removal from the body. Moreover, when the blood circuit was clamped between the two dialyzers, the UF was performed at the 1st dialyzer: at the 2nd one, the dialysate moved to the blood side as a replacement fluid automatically, in terms of the rate of UF. In the clinical evaluation, the clearances of β₂-microglobulin and RBP were 49.3ml/min and 29.2ml/min respectively, where those of the control β₂-microglobulin and RBP were 8.2ml/min and 0ml/min, respectively. Since the dialysate serves as the replacement fluid in the new system, however, the pyrogen and bacteria problem must be solved. To remove them, tap water is subjected to coarse filter, activated charcoal, ion exchange and reverse osmosis treatment, followed by preparation of the dialysate. Clinically, there are no side effects, and the system is safe, effective and practical.

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The response to [Sar¹, ile⁸] angiotensin II (A II A) infusion during sodium depletion and the longterm effect of SQ14, 225 were compared between seven hypertensives with unilateral (US) and four with bilateral renal artery stenosis (BS). Plasma renin activity (PRA) was significantly higher in US than BS during both sodium depletion and repletion. A fall in diastolic blood pressure induced by AIIA infusion was more marked in US than in BS. The ratio of renal venous renin during sodium depletion was significantly higher in US (1.68±0.08) than in BS (1.19±0.08) and was negatively correlated with a fall in diastolic blood pressure induced by A II A infusion. SQ14, 225 showed the same degree of hypotensive effect in US and BS after one month administration. PRA rose and plasma aldosterone decreased equally in US and BS during treatment. There were no significant correlations between the reduction of blood pressure during treatment with SQ14, 225 and pretreatment PRA levels or changes of diastolic blood pressure observed during A II A infusion. These results indicate that the mechanism maintaining high blood pressure is more renin dependent in US than in BS and that the long-term effect of SQ14, 225 might not depend solely on the suppression of renin-angiotensin-aldosterone system.

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Changes in systolic blood pressure, sodium metabolism and renal function were studied in pregnant Wistar rats (WR) and Spontaneously Hypertensive Rats (SHR) during mating, gestation and 8 weeks postpartum periods. Abrupt reduction in systolic blood pressure, around 27mmHg was observed in SHR during a few days prior to delivery, followed by returning to the previous blood pressure within a week postpartum, whereas no such a phenomenon was taking place in WR. Drinking 1% Nacl solution after weaning induced a lower rate of pregnancy and delivery of SHR, in comparison with WR. Although the systolic blood pressure of SHR was raised beyond 200mmHg during pregnancy, it was decreased by about 40mmHg a day prior to delivery, and subsequently returned to the previous value. Sodium space of SHR was significantly increased at the second (33.8±2.7% BW) and third trimemster (30.7±0.4% BW) in comparison to the pre-pregnacy value (28.0±2.7% BW). In addition, sodium space was significantly lower in the third trimester than that of the second trimester (p<0.001). The result of total exchangeable sodium was similar to that of sodium space (p<0.05). Simultaneous increases in inulin clearance and fractional excretion of sodium in SHR were observed at the thirdd trimester in comparison with pre-pregnancy values (p<0.025, p<0.05). The mechanism of reduction in systolic blood pressure prior to delivery in SHR seems to be compplicated by the following factors: 1) an antipressor substance of placenta, 2) a depressor substance of fetal kidney, 3) an endocrinological change, 4) a hemodynamic change during pregnancy, etc. However, the elevation of glomerular filtration rate and fractional excretion of sodium are believed to play an important role on this mechanism.

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The study was designed to explore the mechanism related to abnormal secretion or metabolism of aldosterone in low-renin essential hypertension. Essential hypertension was classified into low- (below 1.0ng/ml/h), normal- (from 1.0 to 6.0ng/ml/h) and high- (above 6.0ng/ml/h) renin group from the results of plasma renin activity obtained after an intravenous injection of furosemide (1 mg/kg) followed by 2 hour ambulation. Plasma aldosterone concentration (PAC), aldosterone secretion rate (ASR), excretion rates of urinary 3α, 5β-tetrahydroaldosterone and aldosterone-18-glucuronide were measured by radioimmunoassay in 50 patients with essential hypertension, 9 with primary aldosteronism, 3 with idiopathic aldosteronism and 11 normal subjects. Aldosterone metabolic clearance rate (MCR) was measured in 8 low-, 8 normal- and 6 high-renin patients with essential hypertension, 5 with primary and 3 with idiopathic aldosteronism and 7 normal subjects. No significant difference of PAC was observed between low-renin group of essential hypertension (6.9±2.6ng/dl) and normal subjects (7.1±1.9ng/dl). Apparently high value of PAC was obtained in primary- (35.4±16.8ng/dl) and idiopathic (21.3±7.2ng/dl) aldosteronism. ASR was significantly low (73.2±21.1μg/day, p<0.05) in low-renin group (normal subjects: 89.2±26.7μg/day) and remarkable high in primary- (449.1±244.3μg/day) and idiopathic (305.0±103.4μg/day) aldosteronism. PAC in low-renin group was apparently situated above the regression line between PAC and ASR which were obtained in normal subjects. MCR was significantly low (710.4±78.81/day/m², p<0.05) in low-renin group and markely high in primary and idiopathic aldosteronism (normal subjects: 843.2±94.61/day/m²). Urinary excretion rate of 3α, 5β-tetrahydroaldosterone was normal and aldosterone-18-glucuronlde was significantly low value of 5.6±2.2μg/day (p<0.05) in low-renin group, and apparently high values of these steroids in primary- and idiopathic aldosteronism were found (normal subjects: 8.1±2.9μg/day). The date suggest that the normal plasma aldosterone concentration in low-renin essential hypertention depends upon the decreased metabolic clearance rate of aldosterone in relation to disturbance of aldosterone glucuronization in the liver and/or the kidney.

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