In order to confirm a pathogenic role of renal tubular epithelial (RTE) antigen in membranous glomerulonephritis, we searched for RTE antigens and anti-RTE antibodies in membranous glomerulonephritis patients. RTE antigens were prepared from normal kidneys by a technique adapted from that of Edgington et al. and Naruse et al. Biopsies from 30 patients with membranous glomerulonephritis (22 patients with primary membranous glomerulonephritis and 8 patients with secondary membranous glomerulonephritis) were examined for the presence of RTE antigens in glomerular immune deposits. In no instance was RTE antigen in glomerular immune deposits. Collected sere from 18 patients with membranous glomerulonephritis (11 patients with primary membranous glomerulonephritis and 7 patients with secondary membranous glomerulonephritis) were assayed for anti-RTE antibodies by indirect im:inunofluorescence and by radioimmunodiffusion. However, they had no demonstrable circulating anti-RTE antibody. These studies suggest that if RTE antigen posseses a nephritogenic potential for human membranous glomerulonephritis, it is probably only rarely expressed.

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The changes of glomeruli and afferent and efferent arterioles in the kidneys from 18 patients with chronic glomerulonephritis, including 9 patients treated with hemodialysis, were studied by histologic and morphometric procedures using serial sections and by electron microscopy. In eight out of nine cases which had not been treated by dialysis, the majority of glomeruli were obsolescent, whereas the rest showed glomerular hypercellularity, thickening of glomerular basement membrane, mesangial sclerosis, adhesions between glomerular tuft and Bowman's capsule, and occasional crescent formation, except for a small number of still intact or hypertrophic glomeruli. Moreover, it was noticed that a process of resorption had subsequently occurred in more than half of obsolescent glomeruli. In the remaining one case, the greater part of glomeruli showed diffuse thickening of glomerular basement membrane, and a small number of glomeruli were obsolescent. In short-term dialyzed kidneys, glomerular changes were nearly similar to those of the former cases which had not been on dialysis. However, in long-term dialyzed kidneys, numbers of glomeruli were considerably smaller than those of non-dialyzed and control kidneys, and almost all of remaining glomeruli showed obsolescence and were in subsequent resorption stage. Electron microscopic studies of these obsolescent glomeruli in resorption stage revealed hypocellular or acellular glomerular tufts, remnants of severely wrinkled glomerular basement membranes, ruins of urinary space filled with amorphous materials, cellular debris, and collagen fibers, small cavities lined by podocyte-like epithelial cells with subepithelial basement membrane, atrophy or loss of epithelium of Bowman's capsule, and fragmentation or disappearance of basement membrane of Bowman's capsule. Shunt formations between afferent and efferent arterioles of obsolescent glomeruli were observed in not only juxtamedullary region but also outer cortex in most of the cases.

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Proximal convoluted tubules in the kidneys from eighteen patients with chronic glomerulonephritis were studied by light and electron microscopy. Nine of these had been treated with hemodialysis. Besides, proximal convoluted tubules at urinary poles of variously affected glomeruli were pursued by using serial sections, in order to clarify the interrelation between morphologic changes of proximal convoluted tubules and those of glomeruli. Grade of atrophy of proximal convoluted tubule generally increased in proportion to damage of parent glomerulus. Proximal convoluted tubules belonging to obsolescent glomeruli were severely atrophic and showed markedly thickened basement membranes. Moreover, proximal convoluted tubules arising from obsolescent glomeruli which were in resorption stage had often disappeared, or showed remnants of fragmentary thickened basement membranes without epithelial cells. It was suggested that atrophy of proximal convoluted tubule progressed in association with evolution of glomerulitis, and finally the atrophic proximal convoluted tubule disintegrated and disappeared. Ultrastructural study of the atrophic proximal convoluted tubules revealed marked decrease in number and length of microvilli, disappearance of lateral and basal interdigita-tions between adjacent cells, almost smooth contour of lateral cell membrane, pronounced small basal cytoplasmic processes, and severe thickening of basement membrane with massive cellular debris. These debris might be originated from such basal cytoplasmic processes of epithelial cells or slender extentions of fibroblasts existing at peripheral part of thickened basement membrane. In this paper three subjects have been discussed: first is the interrelations between morphologic changes of proximal convoluted tubules and those of glomeruli, second is the difference between changes of the proximal convoluted tubules in non-dialyzed kidneys and those in dialyzed ones, and third is disintegration and disappearance process of the atrophic proximal convoluted tubules.

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Present study was performed in order to elucidate pathologic process of distal parts of urinary tubules in kidneys from 9 non-dialyzed and 9 dialyzed patients of chronic glomerulonephritis. Difference of the behaviour between proximal convoluted tubule and distal part of urinary tubule of the same nephron was examined by using serial sections. Atrophy of epithelium and thickening of basement membrane in the distal part of urinary tubule were considerably less than those of proximal convoluted tubule of the same nephron. The distal part of urinary tubule belonging to obsolescent glomerulus showed a pronounced decrease in the outer diameter and lumen. Their epithelial cells evidenced clear cytoplasm, and tubular basement membrane was usually thin. These specific features of distal parts of urinary tubules were frequently observed in long-standing chronic glomerulonephritis, especially surrounding interlobular arteries and obsolescent glomeruli which were in resorption stage. In the interstitium neighbouring these distal tubules, fibrosis and sclerosis were hardly seen and capillary networks were often found out. In the long-term dialyzed kidneys of which most of glomeruli and proximal convoluted tubules had already disappeared, the distal parts of urinary tubules with a decrease in the lumen and clear transformation of the cytoplasms of their epithelial cells were more predominant. Ultrastructurally, the epithelium of the distal part of urinary tubule revealed a decrease in number and size of mitochondria, disappearance of basal and lateral interdigitations enclosing mitochondria, and thin basement membrane. It was interesting that lateral cell membranes of adjacent epithelial cells showed small infoldings or interlocking processes, and there were canaliculi-like areas between adjacent epithelial cells. The significance of these specific morphologic changes in the distal parts of urinary tubules has been discussed.

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Methylguanidine (MG) is known to be one of the potent uremic toxins. Liver, muscle, gut flora or kidney were thought to produce MG; and either creatinine, arginine or guanidinoacetic acid is thought to be a precursor of MG. There is no certified theory about the producing organ or synthesizing pathway. We previously reported that liver and/or kidney might synthesize MG because of their high concentration of MG after intraperitoneal administration of creatinine to rats. In this study, we investigated the synthesis of MG in isolated hepatocytes prepared from normal rats in order to clarify the precursor of MG and to certify its synthesizing organ. Creatinine, arginine and guanidinoacetic acid were added to the incubation medium. MG was separated by high pressure liquid chromatography, and measured fluorometrically after reacting with 9, 10-phenanthrenequinone. The MG production was detected only in the incubation which had creatinine added to them. The production of MG was dependent on the creatinine concentration of medium and the period of incubation. On the other hand, the production of guanidine increased only in the incubations with guanidinoacetic acid. These results indicated that methylguanidine was synthesized in the liver and suggested that creatinine was the precursor of MG. In addition, they also indicated that guanidine was synthesized in the liver and that guanidinoacetic acid stimulated its synthesis.

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Clinical and pathological features of 30 autopsy cases of renal cortical necrosis (RCN) were reviewed and examined. The following results were obtained : 1) age distribution showed peaks in their fifties and seventies. 2) acute renal failure developed in all cases, but in few cases was noted the existence of RCN clinically. 3) such conditions as infection, hemorrhage, and shock, were associated with development of acute renal failure. 4) increase in serum FDP level and platelet count, and prolongation of prothombin time was noted on laboratory examination. Nine cases out of fully examined 14 cases represented definite DIC (disseminated intravascular coagulation), while the remaining 5 cases showed suspected DIC. 5) as the major pathological conditions, malignancies of various organs were most common at autopsy, while obstetric complication was noted in only one case. 6) mild, moderate, or severe parenchymal necrosis of the renal cortex was disclosed histopathologically in all cases. 7) multiple microthrombi-formation in various organs including the kidneys was detected in all cases except one which was complicated by bilateral contracted kidneys. 8) small focal necrosis was scattered in a few extra-renal organs of all cases except the one, while acute extensive parenchymal necrosis of the extrarenal organs could be found in few cases. 9) RCN without extra-renal lesions was observed in 6 cases. These clinical findings, laboratory data, and results of pathological examination indicated close relationship between RCN and DIC. As DIC could be considered to be a human equivalent of generalized Shwartzman reaction, the relationship might suggest that RCN is caused by the pathomechanism common to both DIC and Shwartzman reaction. Part of the RCN cases might be related to a univisceral or single organ type of Shwartzman reaction.

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A patient with fulminant hepatitis and multinucleated giant cells in renal tubulointerstitium was reported, and further study on renal pathology in fulminant hepatitis was attempted on 23 autopsy cases. A 48-year-old man, diagnosed as fulminant hepatitis based on severe jaundice and disturbed consciousness, was treated with dexamethasone, amino acid solution, insulin-glucagon therapy and plasma exchange, but both serum bilirubin and creatinine were increased to 23.7 mg/dl and 3.4 mg/dl, respectively, at the sixth hospital week. Four weeks later he died of pneumonia when serum bilirubin was read at 40.9 mg/ dl. Autopsy revealed submassive hepatic necrosis and acute bronchopneumonia. As for renal lesions, glomeruli and vessels appeared almost normal, but in tubules tubular epithelial cell degeneration, bile casts formation and multinucleated giant cells, which contained bile stained granules and bile casts, were found. Some of the giant cells seen in the interstitium were surrounded with infiltrated small round cells and formed granulomatous lesions. By the way, in 23 patients with fulminant hepatitis, Proteinuria developed in 7, microscopic hematuria in 5 and azotemia in 8 patients. Histological examinations disclosed mild glomerular lesions in 11, degenerative tubular lesions in 11, bile casts in 7 and intratubular multinucleated giant cells phagocytosing bile casts in 4 patients. The seven patients having bile casts or giant cells showed higher serum direct bilirubin (26.1±3.2 mg/dl, mean±S. F, M.) and creatinine (3.06±0.60 mg/dl) levels, compared with the other 16 patients (10.4±1.6 mg/ dl, p<0.005; 0.88±0. 18 mg/dl, p<0.001). These results suggest that fulminant hepatitis frequently accompanied with renal lesions including giant cells probably formed from renal tubular epithelial cells in a process of treatment of bile casts. To the best of our knowledge, this is the first report of f ulminant hepatitis accompanied with tubulointerstitial multinu-cleated giant cells.

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In order to evaluate the relation between renin-angiotensin-aldosterone (R-A-A) system and kallikrein-kinin (K-K) system, single dose tests of captopril were studied in 10 patients with essential hypertension. 25 mg of captopril was administrated in normal sodium diet phase (NaCl 10-12 g/day) and in low sodium diet phase (NaCI 2 g/day) for seven days. Mean blood pressure (MBP), pulse rate (PR), plasma renin activity (PRA), plasma aldosterone concentration (PAC) and plasma bradykinin (BK) were measured before and 60 minutes after captopril. MBP was significantly reduced by captopril in normal and in low sodium diet phases, while PR remained unchanged. PRA was significantly increased and PAC was decreased in both diet phases. BK was increased in both diet phases, but a significant rise (from 23.2±3. 6 pg/ml to 37.1±6.1 pg/ml: P<0.05) was seen only in low sodium diet phase. There was a significant correlation between the reduction in MBP and the increase in BK (r=-0.76, P<0. 05) in low sodium diet phase, however these correlation was not observed in normal sodium diet phase. These results suggested that BK accumulation participated, in part, in hypotensive mechanism of captopril. It was also suggested that not only R-A-A system but also K-K system might have an important role in hypotensive action of captopril in sodium depletion.

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Three sibling (Case 1, a 9-year-old girl, Case 2, a 5-year-old boy, and Case 3, a 3-year-old girl) revealing the Bartter's syndrome are reported. The mother was graviditas 4 and para 3. No cases of the Bartter's syndrome have been recognized in their family nor ancestry. All three cases failed to thrive, and accompanied hypokalemic alkalosis, and showed salt-craving tendencies from infancy. Renin, angiotensin I and angiotensin II as well as aldosterone increased in the plasma of three cases. Blood pressure reacted to the administratetion of angiotensin II, almost normally in Case 1, weakly in Case 2, and very little in case 3. Blood pressure was lowered as a result of the administration of the analogue of angiotensin II and was within the normal range. The platelet aggregation showed an abnormal pattern. In the present cases, the abnormalities of the renin-angiotensin-aldosterone system, the weakened response to angiotensin II and the abnormal platelet aggregation, however, were much milder in the older patient (Case 1) than in the younger patients (Cases 2 and 3). A defect in chloride reabsorption was present in all three cases, and has been thought to be a common abnormality to be concerned about in the Bartter's syndrome. Renal biopsy was done on Case 1 and 2. A morphological study disclosed immaturity of the glomeruli and hyperplasia of the juxtaglomerular apparatus. The proportion of the immature glomeruli was also less in Case 1 than in Case 2.

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Seventeen Subjects on thrice-weekly intermittent hemodialysis were treated with a dose of 40mg gentamicin (GM) (0.6-lmg/kg) given intravenously after each dialysis. Blood samples were withdrawn at 10 minutes after injection, and then before and after each dialysis, and for the calculation of dialyzer clearance blood samples were drawn from dialyzer inlet and outlet tubing after blood flow and transmembranepressure were set at 150-200m1/minutes and 100mmHg. GM concentration was meaured by radioimm-unoassay. 1) Serum levels of GM after the dose and before the next dialysis were 7.2±2.5, 2.4±1.2μg/ml (mean±S. D.) for 43 hours interdialysis period group and 8.0±2.7, 2.2±1.2pg/ml for 67 hours interdialysis period group. 2) Rates of clearance of GM with dialyzers showed wide range of variation from 38 to 138m1/minute depending on the kind of dialyzer tested. Extraction ratio and clearance ratio to creatinine were also varied from 0.33 to 0.61 and from 0.54 to 1.15, respectively. 3) As the GM injection repeated, the predialysis blood levels rose slowly from 0.8±0.6μg/ml after the first dose to 2.1±1.0μg/ml after 5th dose (p<0.02). However, postinjection blood levels (peak GM blood concentration) did not reveal significant rise during this period. There were also no significant changes of pre and postdialysis blood urea or creatinine concentration. After the cessation of GM administration there was marked prolongation of interdi-alysis serum half life of GM and even rise of blood GM levels was observed during interdialysis period. 4) The serum concentrations of GM after single dose, during a multiple dosage regimen, after discontinuation of GM administration are simulated and expressed as a concentration-time curve using Sargent's kinetic equation of uremic toxins with a computer and X-Y plotter. These curves reveal that there is slow but distinct rise in postinjection and predialysis blood levels during a multiple dose and dialysis regimen, but the rise of predialysis blood levels is much greater than the rise of postinjection blood levels. These results suggest that there are significant tissue accumulation and rebound in GM concentration after dialysis, and predialysis GM concentration is best to monitor to determine subsequent GM dose schedule in case of prolonged therapy.

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The case was an alcoholic male of 42 years of age. He was admitted to this hospital because of anasarka and macrohematuria. Laboratory data on admission revealed renal insufficiency, liver dysfunction and a high IgA level in the serum. Peritoneal dialysis was carried out intermittently, because his edema increased and his renal function got worse rapidly after admittance, But, he died of shock during dialysis on the 21st hospital day. An autopsy was performed. Microscopic examinations revealed alcoholic hepatic fibrosis without cirrhosis and diffuse proliferative glomerulonephritis with IgA deposits mainly in the mesangium. About 30% of the glomeruli contained almost circumbient crescents.

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A male Japanese baby weighing 2830g was born to a mother with Addison's disease, who had been treated with hydrocortisone during her pregnancy. He was admitted immediately after birth because of tachypnea and multiple anomalies, i. e., cleft lip, cleft palate, lowset and malformed ear, and retentio testis. During his initial five months of life in the hospital, he suffered from urinary tract infection and septicemia. Also epilepsy, mental retardation and renal and tubular dysfunction were noted during this period. At 13 months of age, he was readmitted with pneumonia. Unexplained fever and polyuria persisted, and dehydration with diarrhea occurred frequently. Finally he died of interstitial pneumonia, intractable dehydration and status epileptics at 18 months of aee. Autopsy findings disclosed bilateral hypoplastic kidney, interstitial pneumonia and malrotation of the intestine. The right kidney was discoid-shaped, ectopic and malrotated. Light microscopic findings clarified a decreased number of glomeruli, dilatation of tubules and hypertrophy of glomeruli three times as large as the normal control. All these findings were compatible with oligomeganephronia. Association of multiple anomalies with oligomeganephronia is said to be very rare. However, among the 44 reported cases which we could examine, , the association was found not to be uncommon. In addition, this condition was discussed from the standpoint of its etiopathogenesis.

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In order to clarify the role of cell-mediated immunity in primary glomerular diseases (PGD), we investigated natural killer (NK) activity by peripheral blood mononuclear cells (PBMC) against K 562 cells and the effect of the PGD sera on NK activity, and comparing to the sera of healthy volunteers. The patients studied included 10 cases of minimal change nephrotic syndrome (MCNS), 19 of IgA nephropathy (IgA-GN), 30 of non-IgA mesangial proliferative glomerulonephritis (non IgA-GN), 14 of membranous glomerulonephritis (MGN), 7 of membranoproliferative glomerulonephritis (MPGN), 2 of rapidly progressive glomerulonephritis (RPGN) and 100 of healthy volunteers as controls. NK activity in patients with nephrotic syndrome of MCNS, MGN and MPGN were significantly decreased compared to that of control group. On the contrary, there was no significant change in NK activity among patients with IgA-GN, non IgA-GN, RPGN, and non-nephrotic stage of MCNS, MGN and MPGN. When normdl PBMC were pretreated with PGD sera, the NK activity in only one case with MPGN was markedly decreased. The sera of other PGD and healthy volunteers did not exert a suppressive effect on NK activity. These data suggest that the deflect in NK cells is seen in patients with nephrotic syndrome of MCNS, MGN and MPGN, and the suppressed NK activity in MPGN can be ascribed to anti-NK cell specific inhibitor in MPGN sera. The deffect of NK cells racy be important in pathogenesis of PGD.

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Male Wistar rats weighing 280 g were exposed to stress for 20 minutes a day over periods of 3 and 12 months (mo.). Stress was applied by bamboo stick-poking to their hips and backs. The blood pressures (BPs) were determined by the tail-cuff method once every two weeks. Histopathological examinations of the kidneys were performed. Spontaneously hypertensive rats (SHRs) at 10.5 months were used to compare the renal changes with those of the stressed rats.The results were summarized as follows;1. BPs in the 12-month stressed group gradually rose to 191±3 mmHg. BPs in SHRs rapidly rose over 200 mmHg for 3 months and maintained that level.2. Focal and semental glomerular sclerosis (FGS) was observed in the rats at 12 mo., and was more intence in stressed rats than in controls.3. Giant hyalin materials (GHMs) were detected in the paramesangium near the vascular pole not only in the sclerotic glomeruli, but also in the non-sclerotic glomeruli. Adhesions of glomerular tuft to Bowman's capsule with GHMs were detected near the vascular pole.These lesions were more frequent in stressed rats than in controls.4. The GHMs were thought to be an early change of FGS.5. These pathological changes were regarded as identical to "Focal and Segmental Glomerular Hyalinosis and Sclerosis" described by Elema et al. (1975) and Couser et al. (1975), the main etiology of which has been recognized to be the aging process.6. Vascular change (PN like lesion) was detected in only one of nine rats in the 12-month stressed group, because the stressed rats showed a more gradual increase in and lower BPs than SHRs.7. FGS in the rats was accentuated by long-term stress. These results suggest that the aging process in the kidneys may be accentuated by long-term stress, but the renal changes in this study have no direct relation to hypertension.

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Peculiar glomerular and renal vascular lesions in proteinuric aortitis syndrome, which have not been described yet, were observed in 2 biopsy and 10 autopsy specimens. The glomerular lesions consisted of 2 distinct lesions. One lesion showed diffusely scattered intramembranous and mesangial electron dense deposits, observed as granular deposition of IgG and C3 by the immunofluorescence study and as being bubble-like in the silver-stained paraffin sections. This was seen in 2 biopsy and 3 autopsy specimens. The other lesion showed a diffuse centrolobular mesangial thickening in a so-called lobular pattern. The matrix appeared swollen and homogeneous generally in accompaniment by hyaline deposits and was fragmented like a mosaic pattern. It was surrounded by patent capillaries forming a rosette-like appearance (“centrolobular mesangiopathy”). This lesion was observed in 8 autopsies but was not seen in biopsy specimens, In addition, 3 specimens showed typical segmental mesangiolysis and mesangiolytic lesion, which was a fine meshwork appearance of the tufts, Interlobular arteries showed various grades of intimal thickening, elastic reduplications, and both afferent and efferent arterioles showed extensive hyaline deposits similar to diabetic nephrosclerosis. However, no luminal obstruction was present. Hyalinized glomeruli of more than 10% was observed in only 3 specimens. The vascular lesions were predominant in autopsy specimens and the grade of mesangial lesions were more severe in a case with advanced arteriolar lesions. In summary: To our knowledge, this is the first report to document that aortitis syndrome has peculiar renal lesions. In the formation of the “centrolobular mesangiopathy”, a long-lasting temperate ischemia caused by the vascular lesions may be implicated.

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