Uptake ratios of ₃H-proline in various elements of the glomerulus of normal and Masugi-nephr-itic mice were investigated by electron microscopic autoradiography to study the function of each element. In both groups, ₃H-proline was mainly taken up by the epithelial and the mesangial cells. No significant difference in value was recognized between the epithelial and the mesangial cells in the normal group. In the Masugi-nephritic group, the uptake ratios increased with time after the glome-rular lesions occurred by the administration of nephrotoxin. In particular, the uptake by the mesangial cell was significantly increased in value one and fourteen days after the administration of nephrotoxin. The above results suggest that the production of collagen by the mesangial cell of the glomerulus may increase with a progress of glomerulonephritis.

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Clinical and immunlogical features of IgA nephropathy were examined through the two ways first, IgA nephropathy was studied in a comparison with 'glomerulonephritis (GN) without IgA deposit', which we defined here as idiopathic GN giving the similar glomerular changes to IgA nephropathy under light microscopy, but lacking mesangial IgA deposits by immunofluorescent staining (IF). IgA nephropathy was defined as idiopathic GN giving proliferative changes with IgA deposits in the mesangium. Seeond, a significance of mesangial IgA deposits was examined in reference to other immunoglobulin in deposits. [I] IF for the immunoglobulins (Ig) and complement components (C') were carried out on renal biopsy specimens obtained from 78 patients with IgA nephropathy and 53 patients with 'GN with out IgA deposit'. Glomerular C3b-receptor activity (C3b-GRA) was also examined according to Gelfand. Serum levels of Ig and C' were measured by single radial immunodiffusion. HLA typing was deter-mined by the method of microcytotoxicity test. Clinical parameters required were determined at the time of renal biopsy as a rule. The Frequencies of glomerular deposits for IgG, IgM, Clq, properdin, C3, C9 and fibrinogen by IF wree significantly higher in IgA nephropathy than that in the other. Serum level of IgA was found elevated in approximately 40% of patients with IgA nephropathy and mean serum level of IgA tended to be higher in IgA nephropathy. HLA-B40 antigen was shown to be significantly higher in patients with IgA nephropathy than that with 'GN without IgA deposit' or normal controls. Unexpectedly, patients with IgA nephropathy were found to be rather predisposed to massive proteinuria, impairment of renal function or progression of glomerular changes. [II] IgA nephropathy was divided into four subgroups as such : group A, 20 patients with deposit of IgA alone in the mesangium; group B, 16 with deposits of 'IgA+IgG' ; group C, 3 with deposits of 'IgA+IgM'; group D, 40 with deposits of 'IgA+IgG+IgM'. The frequencies of mesangial deposits of Clq, factor B and fibrinogen by IF were significantly higher in group D than in group A. The female outnumbered the male in group D on the contrary to group A. Further studies are needed to reveal more specific immunological features of IgA nephropathy.

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Clinical symptoms and laboratory findings in 80 patients with IgA nephropathy were evaluated in order to elucidate the clinical feature of this disease. Tonsillar hypertrophy was found in 17.5 per cent of the patients. The freaquency of the other complications was as follows : hypertension; 16.3%, allergic rhinitis; 12.5%, scleritis ; 10.0%, psoriasis; 2.5%, ichthyosis ; 2.5%, diabetes mellitus; 2.5%, and myasthenia gravis ; 1.3%. As far as the laboratory findings were concerned, glucose intolerance with normal amount of endogenous insulin secretion was shown in 72.6% of the patients with. IgA nephropathy. Elevated plasma renin activity was observed in 57.0% of the patients with IgA nephropathy, but 82% of such patients showed normal blood pressure. Serum IgA (p<0.001) and sernm IgM (p<0.01) levels were elevated and serum C3 (p<0.05) level was decreased. It has been generally considered that systemic complication is absent in IgA nephropathy. This is the first report demonstrating various types of immuological and metabolic abnormalities in this disease. Scleritis, psoriasis, and myasthenia gravis are regarded as autoimmune disorders. It is suggested that some autoimmune mechanism may be involved in the development of IgA nephropathy.

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Twenty-two patients (12 of male and 10 of female, 23-69 years old, endogenous creatinine 8 ml/ min-110ml/min) with stable chronic glomerulonephritis were investigated to elucidate the relationship of plasma vitamin D metabolites, plasma immunoreactive parathyroidhormone, serum creatinine, calcium, phosphate, and endogenous creatinine clerance (Ccr). Plasma vitamin D metabolites were mesured by vitamin D multiple assay methods recently developed in our laboratory. The conclusion followed. 1) Most of these patients revealed normal plasma levels of 25-hydroxyvitamin D. 2) Plasma 1, 25-dihydroxy-vitamin D levels and Ccr were revealed significant correlation (r=0.736), on the other hand, the inverse correlation was noted with plasma creatinine (r=0.58). 3) Plasma 24R, 25-dihydroxyvitamin D levels apparently became low in cases of Ccr below 30 ml/min. 4) The ratio of plasma 1, 25-dihydroxy-vitamin D /Ccr was seemed inverse correlation with Ccr (r=0.6), where as the positive correlation with immunoreactive parathyroidhormone was demonstrated (r=0.72). 5) There was inverse correlation between plasma 1, 25-dihydroxyvitamin D levels and serum phosphate levels (r=0.57). It was suggested that the higher rate of plasma 1, 25-dihydroxyvitamin D levels/Ccr in propotional decreasing renal function might be some metabolic compensatory effect. This phenomenon due to higher levels of plasma parathyroidhormone.

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In the midst of his first climbing, a 18-year-old man developed acute exertional rhabdomyolysis associated with acute renal failure. It seemed to us that most of the causes in our case were owing to dehydration-exercise synergism. Despite of severe hyperuricemia (29.0 mg/dL) and continuation of anuria for three weeks, he recoverd from his illness completely against our apprehension for his restoration. Hypocalcemia (6.2mg/dL), accompanied by mild secondary hyperparathyroidism (C-terminal-iPTH: 0.6ng/ml) and slightly low level of serum 25-OHD (17.0 ng/ml), was observed during an oliguric period. Hypercalcemia in a diuretic phase was not found. After restoration of acute renal failure, the mild elevation of transaminase, which appeared to have relation to liver injury, persisted for four months.

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In order to evaluate the effect of heparin on abnormal lipid metabolism in patients on regular dialysis treatment (RDT), hemodialysis without heparin was performed for 6 weeks on 8 RDT patients using as anticoagulants, synthetic proteinase inhibitor, gabexate mesilate and small doses of aspirin. Various parameters as to lipid metabolism were checked every other week during the 6 weeks of hem-odialysis without heparin and the following 6 weeks of hemodialysis with heparin. Routine blood chemistry and blood counts taken at the start of hemodialysis without heparin, had of changed significantly when rechecked at the end of the treatment. No significant changes were observed in the following: triglyceride (TG), phospholipid, esterified cholesterol, high density lipoprot-ein cholesterol (HDL-C), postheparin lipolytic activity (PHLA), lecithin cholesterol acyltr.ansferase (LCAT) activity, and lipoprotein electrophoretic pattern (LPEP). Total cholesterol (TC) and β lipopr-otein (BL) had increased slightly but significantly by the 4th week of hemodialysis without heparin, but both did not show any significant change by restart of hemodialysis with heparin. The incremental increases of TC and BL accompanying the withdrawal of heparin, may indicate that heparin has a cholesterol-lowering effect to some extent. As very low density lipoprotein (VLDL) and chylomicron cholesterol are thought to be transferred into HDL in the course of the disintegration of VLDL and chylomicron, heparin-induced lipases may accelerate this transfer process by hydrolysing VLDL and chylomicron TG. Judging from the fact that no significant changes in TC and BL were observed when heparin was reinstituted, the cholesterol-lowering effect (if any) of heparin appears to be very weak. There were no significant changes in PHLA, TC, LCAT, and LPEP-abnormalities which are typically observed in RDT patients-suggesting that repeatedly administered heparin in hemodialysis has little effect on abnormal lipid metabolism in RDT patients.

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The present study was performed to know the effects of potassium salts on blood pressure, sodium metabolism, and urinary kallikrein excretion of salt-loaded rats. Fifty-seven male Wistar rats were divided into four groups and fed on (1) a control diet (12 rats), (2) a high sodium diet (high Na group) (15 rats), (3) a high sodium high potassium diet (high Na-K group) (15 rats), and (4) a high sodium high potassium diet which contains iodine and bromine (I-Br group) (15 rats), The rats were raised for 26 weeks and blood pressure, sodium balance, urinary kallikrein excretion, plasma aldosterone concentration, adrenal aldosterone content, and plasma renin activity were investigated. Blood pressure on the 26th week was 125±2 mmHg (Mean ±SE) in the control group, 147±3 mm Hg in the high Na group, 136±2 mmHg in the high Na-K group, and 134±2 mmHg in the I-Br group. The rise of blood pressure of salt-loaded pressure of salt-loaded rats was suppressed by the addition of potassium salts. The addition of potassium salts caused sodium balance more negativeas compared to the high Na group. This tendency was more conspicous in the I-Br group. The naturiuretic action was thought to be a cause of anti-hypertensive effect of potassium salts, After the 10th week, urinary kallikrein excretion was higher in the high Na-K and I-Br groups than in the high Na group. Furthermore, there was a inverse correlation between blood pressure and urinary kallikrein excretion (r=-0.357, p<0.01). These results suggest the possibility that the renal kallikrein-kinin system might be involved in the mechanism where by potassium salts suppress the rise of blood pressure of salt-loaded rats, Factors other than aldosterone were thought to be the cause of the higher urinary kallikrein excretion in the I-Br group, because the adrenal aldosterone content as well as plasma aldosterone concentration was significantly lower in that group than in the high Na-K group.

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The aim of this study was to know the effects of protein intake on blood pressure, sodium metabolism, and urinary kallikrein excretion of salt-loaded rats. Fifty-five male Wistar rats were devided into four groups and fed on (1) a control diet (10 rats), (2) a low protein high salt diet (15 rats), (3) a standard protein high salt diet (15 rats), and (4) a high protein high salt diet (15 rats). The animals were raised for 17 weeks, and the effects of these diets on blood pressure, sodium metabolism and urinary kallikrein excretion were investigated. Blood pressure on the 17 th week was 156±3 mmHg (Mean ± SE) in the low protein high salt group, and 152 ± 3 mmHg in the standard protein highh salt group. These values were significantly higher than 126 ± 4 mmHg in the high protein high salt group. The rise of blood pressure of salt-loaded rats was suppressed by a high protein diet. Fractional urinary excretion of sodium intake was signi-ficantly lower in the low protein high salt group than in other salt-loaded groups. There was a sig-nificant inverse Correlation between fractional urinary excretion of sodium intake and blood pressure. Because the concentration of urea-N and the osmolarity of urine were highest in the high protein high salt group, the osmotic diuresis due to urea might be a cause of larger urinary sodium excretion in the high protein high salt group. Urinary kallikrein excretion was lower in the low protein high group than in the standard protein high salt group, and there was a significant inverse correlation between urinary kallikrein excretion and blood pressure. These results suggest the possibility that high protein intake might suppress the rise of blood pressure of salt-loaded rats by means of larger sodium excretion and the higher activity of the renal kallikrein-kinin system.

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More than fifty cases of plasma cell dyscrasia associated with polyneuropathy and endocrine dis-turbance were reported in Japan Recently, we experienced an autopsy case of this syndrome associated with nephropathy similar to membranoproliferative glomerulonephritis on renal biopsy and autopsy. A 54 year-old man was admitted to Nagasaki University Hospital on Jan 1975. He suffered from 6 anemia, gynecomastia, erythema, lymphoadenopathy, weakness of the lower extremity and pro-teinuria. Electrophoresis of the serum protein showed M protein and immunoelectrophoresis reveald IgG (λ-type). The bone marrow aspiration showed 3% plasma cell including atypical plasma cell with douele nucleus. Predonisolone ane cyclophosphamide was started and the symptoms improved temporarily, but progressive ascites and weakness developed, therefore he died of cachexia on Nov. 1977. On renal biopsy specimens, lightmicroscopic findings showed lobular pattern of glomeruli and thickening of glomerular basement membrane (GBM) associated with partial double contour. Electro-nmicroscopic findings showed irregular thickening of GBM associated with mesangial interposition and with translucent materials in subendotherial space and mesangial areas, On postmortum renal needle biopsy specimens, light microscopic findings showed an enlarged glomeruli with proliferation of mesangial cell and matrix, Immunof luoressence findings of the glo-meruli showed fine granular deposits of IgG, IgA and Fibrinogen in the mesangium and along GBM. Electronmicroscopic findings showed diminution of subendotherial deposits and irregular thickening of GBM associated with circumferential interposition.

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In 92 patients with various renal diseases were studied the effects of urokinase (UK), 60000 I.U./day for continuous 14 days. The improvement rate of clinical symptoms, global improvemen rate (GIR) and global utility rate (GUR) were evaluated at the end of the therapy. Clinical laboratory data (urinary volume, urinary protein, creatinine clearance, etc.) prior to the treatment were compared to those values obtained at the end of the course. Clinical symptoms were judged in 34 patients; the improvement rate was 71.3% in 7 cases with chronic glomerulanephritis (CGN), 56.3% in 16 cases with primary nephrotic syndrome (PNS) and 44.4% in 9 cases with secondary nephrotic syndrome (SNS) ; it was 58.8% in all 34 cases. GIR was 46.2% in 39 with PNS, 45.5% in 11 with SNS and 39.1% in total 92 subjects, and GUR 46.2%, 18.2% and 39.1%, respectively, as well as 33.3% in 36 cases with CGN. In clinical laboratory examinations. Urinary volume increase tended to be significant (p<0.1) and significant decrease of urinary protein was seen in both PNS and CGN (P<0.05). Furthermore, creatinine clearance increase was found to be significant in PNS (p<0.05). The effect of UK was found to be well correlated with U-FDP, S-FDP and fibrinogen level move-ment of typical shapes;that is, improvementrate of 92.3% was seen in patients showed mountain shape movement of U-FDP and 100% of those with similar pattern of fibrinogen level. Moreover, it was 60% in those showed S-FDP change of valley shape. Little improvement was ob-served in those cases of unchanged U-FDP and S-FDP levels. No untoward effect attributable to UK was seen in the present study. Thus, it is believed that the therapy with UK, 60000 I.U./day, is to be beneficial in the glomerulonephritis and nephrotic syndrome, if pathological selection of the patient will be carefully conducted.

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The effects of furosemide on mitochondrial electron trasport system and the in vivo tissue contents of ATP, ADP and AMP were examined. Concentrations of furosemide greater than 10-4M inhibit state 3 respiration supported by glut-amate-malate and succinate of isolated mitochondria from rat liver, renal cortex and renal outer medulla, On the other hand, neither state 3 nor state 4 respiration is inhibited by 4-chloro-5-sulfamoyl anthranilic acid, which is a main metabolite of furosemide. Furosemide inhibits the respiration released by SF 6847 in isolated mitochondria from rat liver, In sonicated beef heart submitochondrial particles, the activities of N ADH-q tochrome c (cyt. c) reductase and succinate-cytm c reductase are sig-nif icantly inhibited by the addition of 4 × 10-3M f urosemide (78.2%; p<0.001, 79, 2%; p<0.001, respec-tively). However, the activity of NADH-DCIP (2, 6-dichloroindophenol) reductase or succinate dehydro-genase is not inhibited. Furocemide causes a reduction of cyt. b and an oxidation cyto c+c1. These data support the conclusion that furosemide inhibits oxidative phosphorylation in vitro by inhibiting electron transport between cyt. b and cytc c+c1. Tissue levels of ATP and total (ATP+ADP+AMP) in rat kidneys are decreased by the infusionn of furosemide (10 and 20 mg kg D.W./hr) and tissue level of AMP is increased, On the contrary, no significant change in the ATP, ADP or total level is observed in rat livers The differential action on kidney and liver might be consistent with its predominant site of action.

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