The relation of ultrastructual alterations of glomerular anionic sites to morphological changes of the glomerular basement membrane (GBM) was studied in biopsies in idiopathic membranous glomerulonephritis (MGN) using polyethyleneimine (PEI) as a cationic probe. The subepithelial deposits did not fix PEI, and only a very few anionic sites were found between subepithelial deposits and adjacent epithelial cells. Thus, anionic sites of the lamina rara externa (LRE) were markedly decreased in number and interrupted by subepithelial deposits in the earlier stages (stage I and II). As the deposits were incorporated into the GBM in the later stage (stage III), the anionic sites of the LRE were restored by a covering of newly formed GBM. A marked loss of the negative charge on the epithelial cell surface coat (ESC) covering the deposits and foot process effacement were persisted during the course of the disease. The anionic sites of the lamina rara interna (LRI) appeared much less altered in any stage of MGN. These findings suggest that subepithelial deposition of immune reactants is associated with focal loss and disorganization of anionic sites on the GBM, resulting in the glomerular barrier function defect.

View full abstract

Enzyme immunoassay (ELISA) has been developed to detect circulating anti-glomerular (GBM) and anti-tubular (TBM) basement membrane antibodies, and optimal plating condi-tions for each step have been determined. Using collagenase-digested GBM or TBM as an antigen, anti-GBM sera from patients with anti-GBM nephritis and anti-TBM sera from patients with anti-TBM nephritis were discriminated from sera of normal controls or of other nephritis patients. The described assay is easy to perform, fast, inexpensive and reproducible.

View full abstract

Urinary acid soluble protein (U-ASP) concentration was measured in 105 diabetic patients and studied on the relations with urinary N-acetyl-β-D-glucosaminidase (U-NAG) activities, serum ASP (S-ASP) concentration, glomerular filtration rate (GFR), HbA1 levels, diabetic retinopathy (Scott's classification) and complications of macroangiopathy. 1) U-ASP index (mg/g·Cr) was 204±69 in diabetics without proteinuria, 245±75 with intermittent protein-uria, 289±116 with persistent proteinuria, and 740±355 with renal insufficiency. U-ASP index showed a significant increase in all diabetic groups than normal control (106±42 mg/g·Cr). 2) U-NAG index was significantly elevated in all diabetic groups than normal control. 3) There was a significant correlation between U-ASP index and U-NAG index. 4) There was no correlation between U-ASP index and S-ASP concentration, GFR, HbAI levels, grading of retinopathy and macroangiopathy. These results suggest that the increased U-ASP index in diabetics is caused by injury of glomerular basement membrane.

View full abstract

Thirty-nine patients with anaphylactoid purpura and persistant proteinuria were divided into 2 groups based on immunofluorescence findings; one with IgA deposits confined to the mesangium (mesangial type, 19 patients), and the other with the deposits in the glomerular capillary wall in segmental distribution, as well as the deposits in the mesangium (capillary type, 20 patients). Electron microscopy revealed dense capillary deposits in 13 of 15 patients examined in the latter group, inevitably including subepithelial ones, in comparison with only 3 out of 14 patients in the former (p<0.005). The mean daily urinary protein was 0.8g and 2.2g, respectively (p<0.05), and nephrotic syndrome developed in 8 patients, all of whom belonged to the capillary type group. In this group mesangial proliferation was more severe, and extracapillary proliferation (small crescents) was found in 14 patients (70 %), whereas only in 4 (21%) of the mesangial type group (p<0.01). However, 8 patients with the capillary type deposits had mild mesangial lesions, in 2 patients even manifesting nephrotic syndrome. During 2 to 15 year follow-up periods, urinary protein disappeared in 13 patients (33%), and only 4 patients exacerbated. However, in the capillary type group 7 out of 13 patients still remained in incomplete remission with moderate proteinuria even after a 5 year follow-up, although the 5 year renal survival rate was 100% in the mesangial and 90% in the capillary type group. These results suggest that IgA deposition in the capillary wall develops in an active phase of purpura nephritis, indicated by appearance of massive urinary protein and by crescent formation, however the activity diminishes in a short time, followed by a stable inactive phase, during which a considerable number of patients are lead to remission and exacerbations scarcely occur.

View full abstract

Fibrinopeptide A (FPA) and Fibrinopeptide B β 15-42 (FPB β) have been deserved remarkablly useful indicators of coagulation and fibrinolysis system. Each one represents the evidence of thrombin and plasmin generation more sensitive than the convensional methods as fibrin degradation products (FDP). Pathological role of coagulation-fibrinolysis system and renal tubular dysfunction in pregnant toxicosis has not been reported previously. This investigation was performed to assess about coagulation-fibrinolysis system and tubular dysfunction on pregnant toxicosis by estimations of FPA and FPB βin urine and plasma, urine, β2-microglobulin (u-βMG), urine β-N-acethyl glucosaminidase (U-NAG) and serum uric acid. Following results were obtainted. 1) In severe toxicosis, FPA and FPB β in plasma and urine have increased tremendously. It means both activities of coagulation and fibrinolysis are enhanced. In mild cases of toxicosis, FPB β was increased, but FPA is not elevated. It suggests fibrinoslysis activity was enhanced only in mild toxicosis. 2) Relationships between plasma FPA and plasma FPB β (r=0.62) and between urine FPA and FPB β (r=0.56) were observed in the cases with severe toxicosis. It suggests secondary fibrinolysic activity has been in proportion to hypercoagulability on severe toxicosis. 3) Plasma FPB β and urine FPB β shows significant relationship (r=0.63), but there is no relationship between plasma FPA and urine FPA. This finding suggests that thrombin generation has increased not only in the kidney but in systemic circulation. 4) There is well proportion to the urine NAG and urine FPB β (r=0.72). This sugests correlation between renal coagulation-fibrinolysis system and tubular dysfunction. 5) Serum uric acid was correlated with plasma FPB β (r=0.55), suggesting a close connection between placental dysfunction and coagulation-fibrinolysis system in pregnant toxicosis. 6) In severe toxicosis, plasma and urine FPA level decreased following urokinase therapy.

View full abstract

Mizoribine is a widely used immunosuppressive drug that was introduced by a Japanese pharmaceutical company. Mizoribine-induced hyperuricemia is characterized by its accompanying phenomenon of reduced renal function. The cases that we present here indicate that hyperu-ricemia, with peak levels 4-7 days after the mizoribine administration, appears when the drug is administered to patients who are on hemodialysis or have mild to moderate renal failure. Furthermore, our 4 cases suggest new mechanisms of mizoribine-induced hyperurice-mia : 1) increased production of uric acid is suggested when the drug is administered to patients on hemodialysis. 2) mizoribine shows an inhibitory activity on the renal excretion of uric acid when the drug is used on patients with mild to moderate renal failure. 3) conti-nuous administration of mizoribine tends to ameliorate hyperuricemia.

View full abstract

To examine whether there are any metabolic defects leading to uremic toxicity associated with peroxidative cell damage, the study was carried out on in 111 patients with chronic renal failure (CRF) in various stages and 44 healthy controls. Serum levels of antioxidant activity (AOA) and malondialdehyde (MDA) were determined by the method of Stocks et al. and that of Yagi, respectively. Red blood cell (RBC) deformability was assayed using a nucleopore filter method. Other clinical parameters including motor nerve conduction velocity (MNCV) were determined. A significantly high level of serum MDA level was found in approx. 20% of dialysed patients, most of whom were severely anemic A correlation between serum MDA level and an index of RBC-deformability was significant (r=0.654, p<0.01), and serum MDA level and MNCV value were inversely correlated (r=-0.324, p<0. 02). The serum AOA levels were significantly low in CRF patients (p<0.001), and the lowest value was noticed in uremic patients requiring the start of regular dialysis therapy (RDT). Sera obtained from patients with low AOA showed a significantly high MDA level (p<0.02). An impaired RBC deformability was shown to be associated with a defective serum AOA. The defective serum AOA levels were restored to a subnormal level during RDT. Among correlations of serum levels between AOA and urea-N, creatinine and other blood chemist. ries, a correlation with serum transferrin level was significant, although the exact role of that needed further studies. It is indicated that the defective serum AOA appears to be an endogenous metabolic consequence of uremic state, and that may contribute to a certain uremic toxicity such as an impaired RBC deformability, anemia and peripheral neuropathy through peroxidative cell damage.

View full abstract

To examine the role of adrenal medulla in elevation of blood pressure (BP) induced by sodium loading, BP, urinary excretion of catecholamines and NEp turnover in kidney were measured in rats treated with or without adrenal demedullation, which were fed on regular sodium or high sodium diet. The BP, heart rate (HR) and urinary excretion of sodium (U-Na) of rats fed on regular sodium diet did not change by adrenal demedullation, while the demedullated rats fed on high sodium diet showed to decrease in BP and HR, and increased significantly in U-Na as compared with those of sham operated rats. The urinay excretion of NEp and Ep increased significantly in response to salt loading. The urinary excretion of NEp of rats fed on regular sodium diet increased by adrenal demedullation but that of rats fed on high sodium diet did not change by adrenal demedullation. The urinary excreted Ep of rats fed on a regular and high sodium diet decreased by adrenal demedullation. The NEp turnover in kidney enhanced in rats fed on a high sodium diet as compared with that of the regular sodium rats. By adrenal demedullation, the NEp turnover in kidney enhanced in rats fed on a regular sodium diet but not that of rats fed on a high sodium diet. These results suggest as follows : (1) the hyperactivities of renal sympathetic nerve and adrenal medulla are elicited by salt loading, and result in BP elevation, that (2) the renal sympathetic activity is enhanced compensatively by adrenal demedullation in regular sodium diet, and that (3 ) the renal sympathetic activity dose not enhance by adrenal de-medullation in a high sodium diet. In conclusion adrenal medulla is cooperative with sympat-hetic nerve activity in regulation of sodium handling and blood pressure, and adrenal medulla play an important role in elevation of blood pressure induced by salt loading.

View full abstract

The present study was designed to investigate the role of dopamine (DA) in the deve-lopment and maintenance of hypertension in SHR. Male SHR at 4 weeks of age, given either basal (0.3%) or high (3.1%) sodium diet, were chronically treated with carbidopa (40 mg/kg/day, for 4 weeks), a peripheral inhibitor of dopa decarboxylase, in order to inhibit the biosynthesis of DA. In these SHRs treated with carbidopa, urinary excretion of DA was significantly decreased as compared with that of SHR with vehicle treatment. In SHRs fed on both basal or high sodium diet, the acceleration in the development of hypertension and the decrease in urinary excretion of sodium were observed in SHR with carbidopa treatment in comparison to those of vehicle administration. In SHRs receiving high salt diet, enhanced excretion of urinary norepinephrine (NE) and epinephrine (E) were observed in rats treated with carbidopa as compared to those of vehicle treatment. Significant negative correlations were observed between systolic blood pressure (SBP) and urinary excretion of sodium and also between SBP and urinary excretion of DA in SHR fed on both basal and high sodium diet. Moreover, significant positive correlation between SBP and urinary excretion of NE and also between SBP and urinary excretion of E were observed in SHR fed on high sodium diet. These data suggest that the decreased dopaminergic activity induced the sodium retention in the body following a decrease in urinary excretion of sodium and that it enhanced the sympathoadrenomedullary activity, especially in salt loading. Therefore the peripheral dopa-minergic mechanism play an important role in the development and maintenance of sponta-neous hypertension in rats.

View full abstract

Glomerular lesions in patients with histologically proven primary biliary cirrhosis (PBC) were studied. Immunofluorescence examination revealed IgA deposition in 7 patients ; both mesangium and glomerular capillary walls in 5, either of them in 2 patients. IgM was positive for the capillary wall in 6 patients in a fine granular pattern, grading from segmental to diffuse in distribution, concomitant with similar deposition of C 3 c in 5 patients. Five out of the 6 patients with mesangial IgA deposition were in advanced stages of PBC (Scheuer's stage III or IV) and the serum IgA level was elevated higher than 600 mg/dl in 4 of the 5 patients. However, there was no ralation between the capillary IgM deposition and the stage of PBC. The serum IgM level was elevated in all 8 patients, but there was no relation between IgM deposition and its serum level. Light microscopy revealed mild mesangial proliferation in 4 patients, but no capillay wall thickening, spike formation or bubble-like appearance was observed. Urinary protein was detected in only one patient averaging at 0.5 g per day, who had mesangial IgA deposition but no IgM deposition. These data suggest that there are 2 types of glomerular immunoglobulin deposition in patients with PBC ; one is the mesangial IgA deposition, probably due to chronic liver damage of PBC, and the other is the capillary IgM deposition, which may be characteristic for PBC.

View full abstract

1086 kidneys obtained at necropsy form 543 subjects aged 1-93 years were studied. 367 subjects were male aged 1-93 years and 176 subjects were female aged 1-87 years. All were examind fresh without fixation. All had died suddenly with no history of renal disease in life. The kidneys were macroscopically normal. In male, kidney weight in adult is 143.5±25.4g (mean ± SD) in left and 140.4±20.3 g in right. In female, kidney weight in adult is 131.6±27.3 g in left and 123.7±25.7 g in right. In paired kidneys, no significant difference in weight existed between the left and right. Kidney weight decrese in subjects over 70 years in male and 60 years in female. In male, kidney size in adult is 11.8 ± 1.05 cm × 6.2 ± 0.74 cm × 3.3 ± 0.63 cm in left and 11.1 ± 0.92 cm × 6.1 ± 0.68 cm × 3.2 ± 0.59 cm in right. In female, kideny size in adult is 11.4±1. 03 cm × 6.0±0.62 cm × 3.2±0.85 cm in left and 11.1±0.80 cm × 6.0±0. 59 cm × 3.0±0.57 cm in right.

View full abstract

The significance of predominant IgM deposition in the glomerulus was studied using renal biopsy cases of various primary as well as secondary glomerular diseases, and the disease entity of so-called IgM nephropathy proposed by Cohen et al. was particularly discussed. Out of 616 renal biopsies carried out during the 10 years' period from 1975 to 1984, 50 cases showed sole or predominant IgM deposition. The incidence was higher in children (19 %) than in adults (7%). IgM deposition was frequently seen in focal glomerular sclerosis (FGS), pre-eclamptic nephropathy and end-stage kidneys at the rates of 100%, 60% and 89% respectively. However, minimal change nephrotic syndrome (MCNS) showed a much lower incidence of 4%. Only two cases of FGS and minor glomerular abnormalities, both 13 years old at biopsy, were compatible with so-called IgM nephropathy. The serum IgM level in the cases with predominant IgM deposition was higher than that in normals, but not significantly higher than that in cases of IgA nephropathy, membranous nephropathy or MCNS. In conclusion, the disease entity of IgM nephropathy seems to be questionable in terms of clinical incidence, particularly in adults.

View full abstract

We report a case, 18 year-old boy, with idiopathic nephrotic syndrome complicated with bilateral adrenal hemorrhage, in this paper. This unfortunate case presented severe nephrotic syndrome (proteinuria 16.8 g/day, TP 3.8 g/100 ml, T-cholesterol 1, 032 mg/100 ml) which did not respond to steroid therapy for about two months from the early to the death in the clinical courses. In autopsy, the renal histopathological features were seen in only juxtamedullary glo-meruli that involved peripheral capillary sclerosing accompanied by an increase in mesangial matrix, local epitherial cell proliferation, foamy cells, and capillary loop adherent to Bowman's capsule. These characteristic features indicated histological diagnosis of early focal glomerulo-sclerosis (FGS). While bilateral adrenal hemorrhage is a direct cause of his death, it remains unclear whether FGS is correlated to the pathogenesis of bilateral adrenal hemorrhage or not. In conclusion, this case is very rare because early FGS without renal insufficiency is complecated with bilateral adrenal hemorrhage.

View full abstract

A retrospective study was conducted on a consecutive series of 62 patients with renal-cell carcinoma treated at the Juntendo University Hospital from 1970 to 1984. The patholo-gical diagnosis of renal-cell carcinoma was established at the time of surgery in 58 cases and post-mortem in 4 cases. They included 41 males and 21 females, aged from 28 to 80 years. The mean age was 57.3 years. The left kidney was involved in 34 cases, and the right, in 28. At presentation, about 75% of them had developed more than one of the three common symptoms (hematuria, pain, and a palpable mass). Among the other cases, 6 cases (10%) had no symptom at all and were diagnosed accidentally by ultrasound study or by CT scanning. Nephrectomy was performed in 58 out of the 62 cases ; radical nephrectomy was performed in 24 cases, and simple nephrectomy, in 34 cases. Lymphnode dissection was done concomi-tantly with radical nephrectomy in 20 cases. An adjuvant therapy was followed in all cases : with radical nephrectomy, radiation in 1 case, immunochemotherapy in 20 cases, and radiation/ immunochemotherapy in 3 cases, and with simple nephrectomy, radiation in 21 cases, immuno-chemotherapy in 3 cases, and radiation/immunochemotherapy in 10 cases. There were no differences as to survival among the varieties of adjuvant therapy. The 5-year actual survival rate was 56.6% overall ; that of pathological Grade 1 (G1) was 91.7%; that of G2, 47.8%, and those of clinical Stage 1, Stage 2, Stage 3 and Stage 4, 79. 8, 77. 8, 47.6 and 0% respectively. There were significant differences as to survival between the low grade and the high grade, or between the low stage and the high stage. In conclusion, the prognosis of renal-cell carcinoma in our series was significantly infl-uenced by the grade and stage, although it was not influenced by any adjuvant therapy.

View full abstract

C3 nephritic factor (C3NeF) is the auto-antibody to C3bBb (C3 convertase of alternative pathway of complement). Since the first report by Spitzer, many methods were developed for detecting the C3NeF by means of immunoelectrophoresis or haemolytic assay with inter-mediate cell. In this paper, we report a new method for the preparation of EAC4b3b cell with zymosan-treated guinea-pig serum (C3-depleted serum or R3) and human C3. And we report the application of this intermediate cell to the detection of C3NeF as in stabilizing assay of EAC4b3bBb cell. In this way, we can de ect C3NeF as IgG purified from membra-noproliferative glomerulonephritis patients' sera.

View full abstract