28 patients with chronic renal failure (C. R. F.), aged 9 to 67 years old, were administered oral carbonaceous adsorbent (AST-120) as conservative therapy. Patients were divided into 3 groups according to their levels of serum creatinine (S-CRTN) . 10 patients of early stage of C. R. F., S-CRTN below 3.9 mg/dl, were classified as group A. 13 patients of value of S-CRTN between 4.0 to 7.9 mg/dl were classified as group E and 5 patients of value of S-CRNT over S mg/dl were classified as group C. Clinical courses were followed by several biochemical parameters before and after administration of the oral adsorbent. The results were evaluated by reciprocal S-CRTN versus time plots and analysis of Wilcoxon test (w-test). 7/10 patients (70%) in group A were revealed effective to oral adsorbent therapy and w.test was significant (P<0.05) . Mean duration of adminsistration of adsorbent was 15.6 ±2.7 (Mean±SENI) months.11/13 patients (84.6%) in group P were effective and w-test was significant (P<0.01) Mean duration, 16.5±2.9 months. 3/5 patients (60%) in group C were effective but w-test was not significant. In patients of group R and C, introduction of hemodialysis were postponed about 2 times longer than control patients of C. R. FF with natural course. We conculuded that oral adsorbent (AST-120) was effective to patients of C. R. FF in conservative therapy, and observed satisfactory outcome even in patients of early stage of C. R. F. like group A.

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The present study was made to investigate the antinephritic effect of SA-446, an angiotensin I converting enzyme inhibitor, on the crescentic-type anti-glomerular basement membrane (anti-GBM) nephritis in rats. The nephritis was induced in male Sprague-Dawley rats weighing approx. 190 g by immunizing with rabbit r-globulin in Freund's complete adjuvant following i. v. injection of anti-GBM serum. SA-446 at doses of 5 and 25 mg/kg was given daily orally to rats from the day after injection of anti.GBM serum(the 1st day) to the 39 th day. SA-446 at doses of 5 and 25 mg/kg showed a tendency to reduce urinary protein excretion on the 12th and the 40th days and plasma choresterol level on the 40th day. In light microscopic observation of renal glomeruli on the 40th day, this drug at both doses remarkably prevented crescent formation, adhesion of capillary walls to Bowman's capsule and f ibrinoid degeneration. In addition, this drug at both doses also caused antihypertensive action from the 5 th day onwards. A highly significant positive correlation was recognized between blood pressure and crescent formation on the 40th day. It is concluded from these results that SA. 446 shows a beneficial action on the crescentic-type anti-GBM nephritis and may exert its action partly through lowing of blood pressure.

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In an attempt to clarify the clinical significance of IgA deposits on the glomerular capillary wall, kidney biopsy specimens obtained from 166 patients with IgA nephropathy were studied. According to the immunofluorescence findings of the renal glomeruli, they were divided into 2 groups. One group consisting of 51 patients (31%) revealed IgA deposits on the capillary wall as well as in the mesangial area (capillary type). The other group of 115 patients (69%) had IgA deposition only in the mesangial area (mesangial type). In the capillary type group, 24 patients (47%) revealed glomerular crescents involving more than 10% of observed glomeruli compared to only 9 patients (8 %) in the measangial type group (p<0.01) . The daily amount of urinary protein excretion prior to the histological examination was 2.0 and 0.7 g, and serum creatinine higher than 1.5mg/dl was marked in 13 (25%) and 3 (3 %) patients, in the respective groups (p<0.01, p<0. 01). Ten of the 12 patients examined in an acute exacerbation, which was indicated by the abrupt appearance of macroscopic hematuria and heavy proteinuria, revealed capillary type IgA deposits (p< 0.01). During a follow-up period ranging from 6 months to 14 years ; with a mean of 3.2 years, renal function declined (serum creatinine > 1.5 mg/dl) in 10 patients (20%) with capillary type and 4 patients (3 %) with mesangial type deposition (p<0. 01). These results disclosed that IgA deposits on the glomerular capillary wall had a close relation to crescent formation, massive proteinuria and decline of renal function, and suggest that the deposits are one of important factors participating in the progression of IgA nepropaty.

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Some cases of glomerulonephritis show the mesangial proliferation like IgA nephropathy (IgA) without IgA depositions in immunof luorescence technique. The author classified these cases as non-IgA nephropathy (non-IgA), and then, studied it in comparison with IgA from the following two viewpoints. (I) Comparison of clinical and histological pictures between IgA and non-IgA Of 748 cases in total, 210 were of IgA and 44 non-IgA. Severe hematuria, especially macroscopic one, was observed more frequently in the former than in the latter. No differences between the two diseases were recognized in the frequency of chance proteinuria/ hematuria and in high serum IgA values, though these parameters have been regarded as characteristics of IgA. IgA revealed more frequently focal / segmental lesions under light microscopy, and alterations of capillary loops as well as hemispherical mesangial deposits by electron microscopy than non-IgA. By immunof luorescence technique, it was proved that non-IgA was composed of various diseases, (II) Comparative prognostic study A retrospective review for declining renal function was made between 60 IgA cases with mild mesangial proliferation and 13 non-IgA patients with the same histological changes in degree. IgA showed more frequently the deterioration of renal function during the follow-up period. The ages of patients and the presence of vascular changes at the time of renal biopsy were described previously as the factors of poor prognosis in IgA. On the contrary, they were observed more frequently in non-IgA than in IgA. Therefore, they were not concerned with poor prognosis of IgA. The focal / segmental lesions, especially segmental sclerosis, observed more frequently in IgA, might constitute such a prognostic factor.

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We examined the role of antigenic charge on the deposition of immune complexes (IC) in murine gloerulia Acute serum sickens nephritis was induced by injecting chemically modified cationic bovine serum albumin (cationic BSA). Controls were immunized with unmodified native BSA (native BSA), All mice were given a primary intraperitoneal immunization with 500 pg of the respective antigens plus Freund's complete adjuvant. After 14 days, we divided the mice into following three groups. The first group was bled and killed for the characterization of antisera and histologic studyo Second group was injected intravenously with 200 μg of ¹²⁵I-labeled each BSA and bled at 5 minutes for measuring the size of IC. Third group was killed at 15 minutes after the second injection for histologic study. In the former renal specimens, neither IC nor antigen was detected in all animals. After the challenge, mice immunized with cationic BSA showed capillary wall deposits of IgG, whereas those immunized with native BSA developed mesangial depositions of IgG. Antibody avidity values in cationic BSA group were significantly lower than those in native BSA group (P<0, 005). The sucrose density gradient ultracentrif ugation study showed that the size of IC in cationic BSA group was slightly larger than 7S. From the above results, we speculated that : 1) The IC depositions on the glomerular capillary walls result from circulating IC formation. 2) The IC composed of cationic BSA effectively binds to the polyanion layer of the glomerular basement membrane. 3) Chemically modified cationization alters the characteristics of BSA, thereby causing the formation of small sized IC.

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Proteinuria and nephotic syndrome frequently occur after renal transplantation We analyzed clinical and histo-pathologic data from 14 recipients (12 living and 2 cadaveric) who developed nephotic syndrome out of 90 living and 11 cadaveric renal grafts surviving over 3 months. Nephrotic syndrome was developed at 22.4 (mean) months post-transplant (range, 3 to 65 months) . The cause of nephrotic syndrome was attributed to transplant glomerulopathy of chronic rejection in 13 recipients and 1 case of renal vein thrombosis. After the onset of nephrotic syndrome, graft f unction deteriorated rapidly, with a 1 year graft surval of 36% and a 2 year graft survival of 10%. Histological characteristics of transplant glomerulopathy was variable capillary wall lesion. Multiple splitting of glomerular capillary wall as a result of subendothelial cell injury and expansion of subendothelial electron lucent layer was common finding.

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Fibrin-Fibrinogen degradation products (FDP) have been found in the blood and urine of many patients with renal disease. This FDP has been regarded as evidence of intraglo-merular coagulation in renal disease. As there are two types of FDP which result from fibrinogenolysis and fibrinolysis, it may be useful to detect the D-dimer which results from fibrinolysis in order to diagnose intraglomerular coagulation. To clarify the role of intraglomerular coagulation in renal disease, blood and urinary FDP D-dimer were examined in comparison with renal histology and fibrinolytic activity in 122 patients with various renal diseases. The defibrinated plasma and urine were subjected to immunoabsorbance affinity chromatography, and then to SDS-polyacrylamide gel electrophoresis. Finally by analysis of densitometry, the fragments X, Y, D, E and D-dimer were detected The D-dimer of renal vein blood in 19 patients was also investigated o The results were as follows: 1) D-dimer in peripheral vein blood was found in 21 of 96 cases (21.9 %) and in urine in 23 of 57 cases (40.4%). 2) In moderate or severe proliferative glomerulonephritis, membranoproliferative glome- rulonephritis, chronic renal failure and systemic lupus erythematosus, higher incidence of blood and urinary D-dimer was shown than in other types. 3) There was no particular relationship between D-dieter of peripheral vein blood and fibrinolytic factors. 4) There was no obvious relationship between peripheral vein blood D-dimer and urinary D-dimer. 5) In urine, the ratio of D-dimer to D fraction (RD-D) was higher than in blood, and there was higher incidence of severe histological findings in cases of high urine and blood RD-D levels. 6) Blood and urinary D-dimer positive cases examined by immunofluorescence had more massive intraglomerular fibrin deposits than D-dimer negative cases. 7) There was no, obvious relationship between the changing levels of FDP, D-dimer and RD_D in arterial blood, renal vein blood and peripheral vein blood.

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Relations between urinary NAG and glomerular lesions were studied. The incidence of elevated urinary NAG levels in normal school childron was only 0.8% (5/575) in contrast to 65.5% (19/29) of patients with prolif erative glomerular lesions. Isozyme A of urinary NAG was 75.0% in normal controls with age over 5 years old, and decreased in patients with nephrotic syndrome with positive urinary protein (p<0.001) and chronic glomerulonephritis (but statistically not significant), presumably because of filtered serum protein which had lower % of isozyme A. Decreased NAG/protein ratio was also noted for the same reason as the decreased isozyme A. The patients who had normal urinary NAG levels despite the presence of proliferative renal glomerular lesions showed increased urinary NAG excretion after standing, walking or routine daily activities in upright position for 3-4 hours.

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We assessed the chronic effects of synthetic rat atrial natriuretic factor consisting of 25-amino acids (ANF) on sodiummwater excretion and blood pressure in conscious rats and also evaluated its antihypertensive effect in rats with hypertension induced by chronic infusion of norepinephrine (NE) Chronic infusion of ANF (150 μg/kg/day) via the jugular vein with an osmotic minipump for up to 3 days failed to affect blood pressure, urine volume, and urinary excretion of sodium, potassium, kallikrein, and prostaglandin E₂ in conscious rats. Although NE (1.8 mg/kg/day i.p.) alone induced a sustained increase in systolic blood pressure (P<0.01), NE (1.8 mg/kg/day i.p.) in combination with ANF (150 μg/kg/day) could not induce an increase in blood pressure. Additional administration of ANF (150 μg/kg/day) to hypertensive rats induced by chronic infusion of NE returned its blood pressure to that of rats administered vehicle alone. These results indicate that chronic infusion of ANF can modulate the vasopressor effect of NE and suggested that endogenous ANF may be involved in the regulation of blood pressure by its vascular action.

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To evaluate the relationship between sympathoadrenomedullary function and sodium intake, urinary output of norepinephrine (NEp), epinephrine (Ep), and dopamine (DA) and NEp turnover of kidney were measured in rats fed on high sodium (13.8 mEq/day), regular sodium (1.03 mEq/day) and low sodium (0.47 mEq/day) diet for 4 weeks. The rats with high sodium diet showed the elevation in blood pressure, pulse rate and sodium retention and augumented output of urinary NEp, Ep, and DA as compared with rats fed on regular and low sodium diets, In NEp turnover which was measured from the decreasing rate of renal NEp concentration after administration of a methyl-p-tyrosine, high sodium intake caused on enchancement of percent decrease of NEp as compared with other diets. From these resuls, it is indicated that sympathoadrenomedullary function and dopaminergic activity appears to increase with sodium loading for 4 weeks. These enchanced function and activity may participate in the increase in blood pressure and natriuresis at sodium loading.

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The renal function (BUN and Cr) was retrospectively evaluated before and during administration of captopril (angiotensin I converting enzyme inhibitor) in patients with essential hypertension (n=8), renal hypertension (n=5), hypertension with chronic renal failure due to renal tuberculosis (n=1, solitary kidney) and renovascular hypertension (n=8, bilateral (n=6) and unilateral (n=2)), Captopril (daily dose 37.5150 mg) was given from 1.5 months to 48 months in these patients whose blood pressure was not controlled below 150/100 mmHg following administration of other antihypertensive drugs such as diuretics, vasodilators, calcium-antagonists and β-blockades. Renal function did not deteriorate following administration of captopril in patients with essential hypertension. On the other hand, renal function deteriorated in two out of five cases with renal hypertension, in the hypertensive patient with chronic renal failure due to renal tuberculosis, and in two (only bilateral) out of eight cases with renovascular hypertension. Especially, renal function deteriorated rapidly in one case with renal failure due to renal tuberculosis and in one case with bilateral renovascular hypertension, which improved rapidly after discontinuing administration of captopril. The patients with renal and bilateral renovascular hypertension in whom renal function deteriorated had high plasma renin activity and serum creatinine level of more than 1.5 mg/dl before administration of captopril. Serum potassium was elevated following administration of captopril in all of 5 cases with renal hypertension, and in the hypertensive patient with renal failure, and in three out of eight cases with renovascular hypertension. These findings suggest that captopril should be carefully administered in patients with renal and bilateral renovascular hypertension.

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To investigate the role of sympathetic activity in the pathogenesis of hypertension, the responses of plasma and urinary catecholamines after quiet standing, two hours' ambulation and furosemide administration were studied in patients with essential hypertension (WHO stage I and II) and in normal subjects. Plasma renin activity (PRA), plasma arginine vaso pressin (PAVP), urinary sodium excretion and hemodynamic parameters (HR, CI and TPR) were also compared in both groups. 1) Although plasma norepinephrine (PNE) levels at rest showed a range from normal to relatively high in hypertensive subjects, the mean PNE level was significantly higher than in the normal controls. However there was no significant correlation between PNE level and blood pressure in these patients. 2) Increase in PNE levels after quiet standing for ten minutes, two hours' ambulation and the intravenous administration of 20mg furosemide was less in hypertensive subjects compared with normal controls, but there were no significant differences with respect to blood pressure, HR, CI and TRP. 3) There was no significant difference in plasma epinephrine levels at rest and after the loading tests between hypertensive subjects and normal controls. The changes in blood volume calculated from hematocrit were comparable in both groups after the loading tests. Increases in PRA and PAVP levels were also less after the loading tests in hypertensive subjects. 4) Decreases in sodium excretion and urinary dopamine excretion after two hours' ambulation in hypertensive subjects were greater than in the normal controls. These results suggested that blood pressure would be maintained by enhanced vascular reactivity to vasoactive substances, especially to norepinephrine, in essential hypertension and that the greater decrease in urinary dopamine excretion would contribute to the greater decrease of sodium excretion together with a change in the renal hemodynamics after ambulation in essential hypertension, thus contributing to the pathogenesis of essential hypertension.

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Suppressed plasma aldosterone concentration (p-Ald) in relation to plasma renin activity (PRA), termed as hyperreninemic hypoaldosteronism (HH), has been shown to occure in some patients with critically ill patients. We investigated the incidence of this new entitiy of HH in 32 patients (19%). None of these HH patients presented with symptoms related to hypoaldosteronism, such as hyperkalemia or metabolic acidosis. There were no significant difference in serum sodium, potassium and creatinine levels between the hypotensive (n=8) and normotensive (n=24) groups of overall critically ill patients. Arterial blood oxygen tension were slightly lower but not significantly different in both groups. p-Ald and 18-OH corticosterone (18-OHB), the aldosteone precursor were slighty lower, and PRA and p-Aid/PRA ratio were somewhatlower in hypotensive group. However, there were no significant differences in any of these parameters. Plasma cortisol was significantly higher in hypotensive group (p<0.05), suggesting much potent stress in this group. When all the patients were subclassified into high PRA (PRA more than 3.0 ng/ml/h) and normal or low PRA according to the basal PRA levels, p-Ald and p-Ald/PRA ratio were significantly lower (p<0.05) in hypotensive group. In three of six patients who developed HH, episode of hypotension was noted, while in the remaining three patients hypotension was not evident. From these results, it is concluded that HH may not be a rare complication of critically ill patients. However, symptomatic HH is infrequent, suggesting HH is either imcomplete or transient. A possible site of impairment in aldosterone biosynthesis might be both in early and late steps of synthesis. The etiology of HH in critically ill may not be explained solely by hypoperf usion of adrenal glomerulosa, since there appeared to be no significant linkage between known duration or severity of hypotension and the development of HH the present series.

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It has been reported that hemoglobin Al (HbAl), which is increased in patients with renal failure, is formed by carbamylation of Hb by cyanic acid derived from urea. Carbamylation is a non:enzymatic and non-specific reaction and may occur at some amino groups of proteins other Hb and peptides. We previously reported that the levels of carbamylated plasma protein were elevated in patients with renal failure and the biological activity of carbamylated L-triiodothyronine (T₃) was reduced than that of T₃. In the present study, insulin and 1-24 ACTH were incubated with cyanic acid to prepare carbamylated insulin and carbamylated ACTH. The resultant carbamylated insulin and carbamylated ACTH was able to be identified by the new peaks which were different from insulin and ACTH on high performance liquid chromatography (HPLC). According to increase in the concentrations of cyanic acid and duration of incubation, the areas of these new peaks increased, respectively. Therf ore, it was considered that these new peaks could be regarded as those of carbamylated insulin and carbamylated ACTH. It is suspected that in patients with renal failure those hormones in the blood may be formed to be carbamylated following with resultant decreased biological activities as well as carbamylated T₃. This is important in considering the endocrine function in petients with renal failure.

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