In order to verify whether cell mediated immunity and circulating immune complexes play a role in the pathogenesis of IgA nephropathy, cell mediated immunity was studied in T cell, B cell subsets, T cell function and the influence of monocytes on immuno-globulin production in patients with IgA nephropathy. CIC were measured by using Clq EIA and anti C3 EIA. Relation between CIC and T cells and monocytes were also studied. The results were followed as. 1) The percentage of Leu 2a cells in peripheral lymphocytes was significantly lower and that of Leu 3a cells higher in patients with IgA nephropathy compared with other groups, meaning that an elevated Leu 3a/Leu 2a cell ratio was observed in patients with IgA nephropathy. 2) IgA T cell helper activity was significantly elevated and IgG and IgM T cell helper activity were also slightly elevated in patients with IgA nephropathy. 3) The higher incidence of IgA immune complex was observed in patients with IgA nephropathy compared with other groups. 4) IgA T cell helper activity in patients with positive IgA-IC was significantly more elevated than in patients with negative IgA-IC. 5) The percentage of monocytes which IgA granular deposits were detected in the cytoplasma or on the cell surface in patients with IgA nephropathy was signficantly higer than in healthy subjects. 6) An enhancement of IgA production was observed when monocytes from patients with IgA nephropathy were added into pokeweed mitogen stimulated coculure with T cells and B cells from healthy subjects. 7) An enhancement of IgA production by T cells treated with IgA-IC was observed compared with T cells treated with IgG-IC or IgM-IC, 8) An enhancement of IgA production by monocytes treated with IgA-IC from IgA nephropathy patients was revealed compared with monocytes treated with IgG-IC or IgM-IC.

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In order to clarify the difference of hemodynamics between subcortical and juxta-medullary glomeruli, we attempted to study an aspect of branch of afferent arteriole at the vascular pole, the observation of intraglomerular capillary anastomoses, and the measure-ment of inside diameter on the afferent and efferent arterioles by the scanning electron microscope (SEM) using plastic model of the glomeruli. This experiments were performed on 13 months' old Sprague-Dawely male rats. By SEM, the ovale shaped impression (possible representing the endothelial nuclei) in afferent arterioles and longitudinal folds in the efferent arterioles were seen. The afferent arteriole after reaching the vascular pole of glomerulus, almostly divided into three or four branches, approximately 6O% of glomeruli in all cases. However the differ-ence of number and shape of the arteriolar branches between both layers were not sig-nificant. Concerning the anastomosis of glomerular capillaries, 4 cases (including FSH glomeruli) were mostly observed T-shaped anastomosis. The results of the measurement of inside diameter of afferent and efferent arterioles, the afferent arterioles in the sub-capsular glomeruli were larger than the efferent arterioles. Nevertheless the inside diameter of the efferent arterioles in the juxtamedullary glomeruli were nearly equal or larger than the afferent arterioles, statistically (t-test). Furthermore, standard deviation of the numerical value of efferent arterioles in the juxtamedullary glomeruli were seen great variation. Judying from these results, it may be supposed that glomerular hemo-dynamics and function of individual glomeruli in subcapsular cortex are approximately equal. While in juxtamedullary ones, they may be different hemodynamics and function in individually. There was no significant difference between minor and FSH glomeruli.

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Tubulo-interstitial renal lesions were definitely induced in BALB/c mice and moder-ately induced in C3H/He mice but not in C57BL/6 mice by several intraperitoneal injections of carbon tetrachloride (CCl₄).In the sera of CCl₄-treated mice with renal lesions, anti-renal tubular epithelium (RTE) autoantibody was detected. Induction of these renal lesions was strongly inhibited by the pretreatment of whole body irradiation at 300 rad. And the presence of anti-RTE autoantibody in the sera of CCl-treated mice and the degree of blast formation of spleen cells from these animals were also markedly decreased by the irradiation. According to these results, induction of tubulo-interstitial renal lesions seen in the CCl₄-treated mice seems to be derived from strain variation of sensitivity to CCl₄ and be caused by the combination of direct cytotoxic effects of CC14 and radiosensi-tive immune systems activated by this agent.

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Using electronic scanner with echo-histogram analysis, quantitative estimation of liver-kidney contrast were measured in 33 mesangial proliferative glomerulonephritis. Histological changes and the establishment of indices of glomerular lesion (IGL) and tubular atrophy (T/S) in a renal biopsy specimen were also examined. In normal subjects, mean value of difference between liver and kidney (L-K) was 3.3±1.96 and liver paren-chymal echogenicity was slightly higher than that of the kidney. In 33 patients, L-K value was found to be positively correlated with creatinine clearance (r=0.778, p<0.001) and Fishberg's maximum (r=0.636, p<0.001), negatively correlated with IGL (r=0.708, p<0.001) and positively so with the mean value of T/S (r=0.856, p<0.001). These results indicate echo-histogram analysis such as L-K value reflect to renal interstitial injury and thus its clinical application could be useful for the evaluation of renal diseases.

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In order to clarify the relationship between the tubulo-interstitial lesions and the sub-epithelial deposits along the glomerular capillary wall in membranous nephropathy (MN), participation of renal tubular epithelial antigen (RTE) and HLA-DR related antigen (Ial) in pathogenesis of the disease was studied. Twenty-nine biopsied and one autopsied kidney specimens obtained from 30 patients with MN (14 males and 16 females) were examined with the indirect immunofluorescence technique using monospecific rabbit anti-serum against human RTE and monoclonal anti-human Ial murine antibody. Fine granular deposits of RTE along the glomerular capillary wall was noted in five patients (17%), two with gouty kidney, one with malignant rheumatoid arthritis and two with idiopathic MN. These positive patients had moderate to severe tubulo-interstitial lesions, In 17 patiens (57%), lal antigen was diffusely expressed in tubular epithelial cells and the grade showed a positive correlation with the grade of tubulo-interstitial lesions (rs=0.579, p<0.001) . In addition, granular expression of Ial antigen in tubular epithelial cells was also observed in all RTE positive, but not in negative patients. Based on these results, it has been suggested that RTE may be involved in the pathogenesis in some patients with MN accompanied with tubulo-interstitial lesions and consequent aberrant Ial expression in tubular epithelial cells may play an important role in recognition of RTE as non self.

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Effect of oral sorbent (AST-120) on clinical courses of patients with chronic renal failure (CRF) has been studied in relation to plasma levels of uremic peak 2a by high performance liquid chromatography. Subjects were thirty cases whose data of plasma levels of creatinine (Cr) and peak 2a were available for a long time of 5-30 months. Sixteen patients administered AST-120 (A group) were compared with fourteen control patients (C group). In A group, prolongation of period until initiation of hemodialysis (HD) and suppression of progression of CRF were observed as previously reported. In these subjects, plasma level of 2a increased progressively with time in C group, however the changes were small in A group. Suppression of 2a in A group was more clearly seen by examining the change of 2a/Cr with time and with plasma Cr as a monitor of progression of CRF. These data combined with previously reported results suggested that rapid deterioration of 2a clearance in C group was suppressed in A group. Thus removal of 2a from body fluid in A group was likely attributed to renal excretion of 2a, in addition to direct adsorption of 2a by AST-120 in digestive tract, which possibility was shown by existence of 2a in gastric juice and bile of patients with CRF. On the other hand, plasma levels of vitamin B₁₂ and 25-OH-D stayed within normal range in A group as well as in C group, indicating that AST-120 did not affect plasma vitamin levels of patients. Such fact and also the clinical effect of AST-120 above described may be explained by taking it into account that AST-120 preserve renal function by suppression of toxic substances such as 2a. Further clinical study is to be continued on effect of AST-120 in relation to the renal function.

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We made a comparison between different buffer compounds by observing their effects on the kinetics of guanidino compounds (GC), We determined the blood concentration of GC in patients on maintenance hemodialysis using sodium bicarbonate and acetic acid by high performance liquid chromatography. In both the sodium bicarbonate and acetic acid dialysis, guanidinosuccinic acid (GSA), guanidinoacetic acid (GAA) and creatinine (CRN) were found not to accumulate in erythrocytes, whereas methylguanidine (MG) was found to be accumulative. The MG concentration in the plasma and erythrocytes at the start of dialysis using sodium bicarbonate was significantry higher than that in the acetic acid dialysis. No significant differences in GSA, GAA and CRN levels were observed between the two dialysis methods. The MG removal rate in erythrocytes and the amount of MG removed in one month in the sodium bicarbonate dialysis were significantry low compared to those of the acetic acid dialysis. An increase in protein-bound MG due to a rising pH level while on dialysis is considered to be responsible in part for a decrease in MG dialysis efficiency using sodium bicarbonate.

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The renal sodium metabolism in spontaneously hypertensive rats (SHR) plays an im-portant role in the development and maintenance of hypertension. An investigation was carried out to detect the difference in the renal sodium handling between SHR and Kyoto wistar rats (WKY). Renal clearance was studied during infusion of 3.0% sodium chloride solution. In addition, micropuncture study with microinjection and microdissection methods was carried out to investigate the sodium and water excretion. These excretion rates were less in SHR than in WKY during the infusion of 3.0% sodium chloride solution. The recovery rate of urinary 22Na following proximal tubule microinjection was lower in SHR than in WKY, whereas there was no difference in the distal tubule. The difference in renal sodium transport between SHR and WKY may be due to increased sodium reab-sorption in the proximal tubule of the nephron in SHR.

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To assess the possible roles of atrial natriuretic factor (ANF) in the regulation of blood pressure in spontaneously hypertensive rats (SHR), we performed two series of experiments. Firstly, we studied hypotensive, natriuretic and diuretic effects of ANF in pentobarbital-anesthetized adult SHR and age-matched Wistar-Kyoto rats (WKY). A synthetic ANF of 25 amino acid residues was intravenously administered as a bolus in doses of 0.1μg/kg, 1.0μg/kg, 2.5μg/kg and 5.0μg/kg. In SHR, a significant decrease in mean arterial pressure (MAP) was observed at the dose of 1.0μg/kg, and MAP decreased in a dose-dependent manner. On the other hand, in WKY group, the decrease in MAP was observed at the dose of 5.0μg/kg. The diuretic and natriuretic effects of ANF were observed at the dose of 2.5μg/kg in SHR and 5.0μg/kg in WKY. Secondly, we also studied chronic effect of ANF on the development of hypertension in 6-week-old SHR The SHR, on regular diet or given 1% NaCI solution for drinking, were continuously infused into the jugular vein by osmotic minipumps with ANF (150μg/kg/day) or vehicle (physiological saline) as controls for up to 14 days, ANF attenuated transiently the development of hypertension in the sodiumloaded SHR. But the blood pressure returned to control levels by day 5. In SHR on regular diet, ANF did not affect the development of hypertension. In addition, ANF did not induce any significant changes in urine volume, fluid intake, urinary sodium, potassium and kallkrein excretion in SHR on both sodium conditions when compared to those in vehicle-infused SHR. These results indicate that there may be a significant difference in the sensitivity to diuretic, natriuretic and hypotensive actions of ANF between SHR and WKY. Moreover, they suggest that ANF may exert some roles by its vascular effect at the early stage of development of hypertension in SHR on sodium loading.

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Ratios of plasma levels of β-thromboglobulin to platelet factor 4 (β-TG/PF-4), which were regarded as a most reliable indicator of platelet activation in vivo, were followed in 52 subjects with essential hypertension at different stages of WHO classification (WHO I 30, WHO II 19, WHO III 3 cases) and in 20 age.matched normotensive controls, β-TG/ PF-4 ratios in hypertensive patients at WHO stage I (3.93+0.19), stage II (5.31±0.35) and stage III (6.56±0, 12) were significantly higher than those of normotensive controls (3.13±0.19). These results suggest that the platelet hyperfunction seen in hypertensive patients has an important role in the development of hypertensive vascular lesions. In another study, changes of blood pressure and β-TG/PF-4 ratios were compared in 19 subjects with essential hypertension at WHO I to II stage after 4 days of feeding with normal (12g/day of NaCI was used by cooking), slightly NaCI restricted (6g/day) or highly NaCI restricted (0g/day) diets Mean blood pressure was reduced by 7 mmHg after slightly NaCI restricted diet and by 22 mmHg after highly NaCI restricted diet. β-TG/PF-4 ratios after slightly and highly restricted NaCI diets were 4.27±0.39 and 4.04±0.22, respectively. These values were significantly higher than those of after normal NaCI diet (3.44±0.25). The reduction of NaCI intake induces an activation of platelets in vivo, while it brings about a significant reduction of blood pressure. These results indicate that it seems to be important to consider the change of platelet function induced by NaCI restriction, when we are going to treat the hypertensive patients with the reduced dietary NaCI intake.

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It has been reported that the glomerular deposits detectable by immunofluorescence staining for IgG are completely dissociated after incubation of tissue sections with human γ-globulin, Seven cases of idiopathic MN, three of MPGN and seven of LN were demon-strated IgG deposits along glomerular capillary walls in granular pattern and were con-firmed that the IgG in glomeruli were dissociated after incubation with human γ-globulin, but not with sheep, rabbit or rat γ-globulin, Furthermore, the dissociation of IgG were observed following incubation with plasmin-treated, PEG-treated, sulfonated human γ-globulin and Fc fragments, but not pepsin-treated human γ-globulin, indicating that Fc fragment play an important role for the dissociation. On the basis of these findings, all patients were treated with large intravenous dose of plasmin-treated globulin (5 g/day, 6 times for two weeks). In 14/17 patients the urine protein and/or hematuria remarkably decreased or disappeared within 7 days to 40 days During 3 years of observation 14/17 patients with these renal diseases could be maintained in improved status from nephrotic syndrome. No untoward effects of γ-globulin therapy were observed. Thus, administra-tion of high-dose intravenous γ-gloubulin is useful treatment for MN, MPGN and LN.

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Screening urinalysis of 89, 137 (72.4%) out of 123, 148 students in Nagoya University were carried out from 1972 to 1985. The percentage of proteinturia and hematuria were 5.4/ and 1.1% respectively at screening test. Renal biopsy was performed in 98 students with chance proteinuria and/or hematuria. The following results were obtained. Minor glomerular abnormalities were shown on the renal specimens in 50.0% of biopsied cases on light microscope. Group of isolated hematuria had the mildest histological finding, comparing with group of proteinuria alone and that of both hematuria and proteinuria. Moreover, group of proteinuria alone showed milder histological changes than that of both hematuria and proteinuria. Immunofluorescent study was carried out in 49 cases. IgA nephropathy accounted for 44.9% of these cases.

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The patient was a 7-year-old girl who was diagnosed as nephrotic syndrome at the age 4. On admission, she had a steroid treatment, but proteinuria was not disappeared Penal biopsy was performed three years after the onset because of persistent proteinuria. Light microscopic examination revealed focal segmental mesangial and endothelial cell proliferation in the glomerulus, therefore focal endocapillary proliferatioe glomerulo-nephritis was diagnosed. Electron microscopically, linear intramembranous dense deposits were found segmen-ta11y and dense deposit disease (DDD) was diagnosed. Apart from these linear deposits, subepithelial deposits (hump) were recognized in the GBM, and also peculiar fingerprint like crystaloid structure were found in the cytoplasm of epithelial cells. As a rule, DDD is thought to be poor prognosis. However, renal symptom such as proteinuria and serum level of complement were ameliorated after renal biopsy in our case, It was suggested that the glomerular lesion at the time of renal biopsy might become milder and improved when compared with that of the onset.

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We studied the effect of heparin on the in vitro production of angiotensin I by active and inactive renin. Blood samples (5 ml) were collected into chilled Vacutainers (Neotube 5 ml) containing EDTA-NA2 (7.5 mg, granules) or heparin (143 units, powder) as antim coagulant. Activation of inactive renin was done according to the method reported by Lumbers. Plasma renin activity (PRA) was measured by radioimmunoassay. Nonacidified (active renin, ARC) and acidified (inactive renin, IRC) plasma was added to sheep reninn substrate, respectively, with angiotensinase and converting enzyme inhibitors. The amount of angiotensin I thus generated was quantified by radioimmunoassay. We compared PRA, ARC and IRC between the EDTA-treated and heparinized plasma in the healthy subjects and the hypertensive patients. Heparin did not affect the determination of PRA and ARC by radioimmunoassay. However, IRC of heparin-treated plasma was significantly lower than that in the EDTAm treated plasma (healthy subject p<0.05, hypertensive patient p<0, 01). These data sug-gested that heparin did not affect the in vitro production of angiotensin I by ream and inhibited the acid-activation of inactive renin. Therefore, it was concluded that coagula-tion system played some role in activation of inactive renin by acidification.

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In an attempt to clarify the participation of immune deposits in progression of glo-merular lesions, relationship between electrondense deposits, especially subepithelial deposits observed by electron microscopy, and light microscopic and clinical findings in 131 patients with IgA nephropathy and 30 with purpura nephritis were studied, Capillary dense deposits together with mesangial deposits were observed in 16 (53%) patients with purpura nephritis in comparison with 46 (35%) with IgA nephropathy, especially subepithelial deposits being more frequently observed in purpura nephritis (15; 50%) than in IgA rephropathy (23; 18%) (p<0.005). In addition, patients with subepithelial dense deposits showed heavier proteinuria with a mean of 1.9+0.2 g/day in IgA nephropathy and of 2.0±0.3 g/day in purpura nephritis, and higher incidence of cellular crescent (9; 39 and 12; 80%, respectively), Furthermore, 5 out of 9 patients with IgA nephropathy, who were in an acute and active phase manifested by an abrupt appearance or increase in urinary protein and gross hematuria, showed subepithelial deposits. In purpura nephritis, 9 of 10 similar patients, all 8 with nephrotic syndrome and 3 with azotemia (Cr>1.5 mg/dl) disclosed subepithelial deposits, Although both daily urinary protein excretion and incidence of cellular crescents were higher in patients with purpura nephritis than those with IgA nephropathy, exacerbations scarcely occurred and prognosis was favourable in the former as compared to the latter, which showed a slowly progressive clinical course. These results suggest that subepithelial deposits develop in the acute and active phase in both diseases but cause different clinical courses as observed in the two diseases, favourable in purpura nephritis and progressive in IgA nephropathy, through difference of duration in disease activity, transient in the former and persistent in the latter.

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Administration of Mexiletine were performed in 7 patients with hige grade ventricular arrythmias (over Lown grade 3) who were recived maintenance hemodialysis. The change rate of 3 cases showed over 33% in number of VPC during 24 hours, Also, 5 of 7 cases inproved on Lown grade, and 6 of 7 cases inproved on clinical symptons, other one case had unchanged. Mexiletine was removed during hemodialysis, why Mexiletine clearance was 42.4± 10.7 ml/min, Blood chemical parameters and mean arterial pressure were unaffected by administration of Mexiletine, Administration of Mexiletine was comparatively safety on main-tenance hemodialysis patients.

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