Glomerular clearing system was histologically studied to see what role it played in the flourishing, resolving and healing stages of Arthus-type nephritis in rabbits with intravenously injected colloidal carbon or ligation of thoracic duct. In the glomerulus, poorly soluble immume complexes were found within mesangial channels, a route for the egress of macromolecules from the peripheral mesangium through the hilus into the juxtaglomerular apparatus, other than phagocytosed by polymorphonu-clear leukocytes. However, in the flourishing stage the immume deposits supplied to the external mesangial matrix seemd to originate in that made in the periglomerular blood capillary. Severer glomerulitis was observed under the condition of lymph stasis and juxtaglomerulitis, which was composed of inactive monocytes and plasmocytes, appeared late from the resolving stage. Coincidentally, stagnant amorphous, electron dense material was seen around the border between the external and internal mesangium or the wall of the efferent arteriole at the reflection site of Bowman's capsule. These features of juxtaglomerulitis may be explained by stagnant deposits transported upstream through mesangial channels. Carbon particles within mesangial channels were finally taken up by mesangial cells, whose endocytotic phagosome settled down until three weeks of the healing stage. Mesangial blebs or pseudopods protruding in the capillary lumen were observed in the resolving stage, the injection of colloidal carbon and the ligation of thoracic duct. The endothelium was lifted by mesangial blebs from the juxtamesangial portion and seemed to interrupt the capillary blood stream. Mesangial influx was increased because of partly desquamation of the endothelium and macromolecules tended to accumulate in the subbasement membrane of the paramesangium. It's suggested that focal segmental sclerotic and adhesive lesions in the healing stage are correlated with the degree of juxtaglo-merulitis and the peripheral mesangial blebs.

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To 13 uremic patients with secondary hyperparathyroidism, 4μg of 1, 25 (OH)₂D₃ were given orally twice a week for 4 weeks. Intact PTH values fell from 488.3+84.2 to 235.2 +59.6pg/ml (Mean±SE, p<0.01), while serum total and ionized calcium elevated from 10.3±0.2 to 11.8+0.6 mg/dl (p<0.01), from 1.43±0.03 to 1.64±0.06 mmol/l (p<0.05), respectively, in 9 patients whose initial intact PTH level had been below 1000 pg/ml. The other 4 patients, of whom intact PTH level had been above 1000 pg/ml, did not show significant change in intact PTH values, though serum ionized calcium elevated slightly after this treatment. The correlation curve, determined by ionized calcium and intact PTH values in each period, was found to shift in only 2 out of 5. During the 4 weeks of high dose oral 1, 25(OH)₂D₃ therapy, mean blood pressure elevated from 92.4+3.3 to 103.5+3.5 mmHg (p<0.01) in general, and 7 patients out of 13 complained of mental irritability. These data suggest that oral administration of high dose 1, 25 (OH)₂D₃ suppresses PTH secretion of uremic patients directly, however, reliability of this effect is still controversial. Indication of this therapy and adverse effects caused by rapid increase in serum calcium should be studied in more detail.

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Maximum binding of ouabain to erythrocytes (Bmax), serum K, urinary aldosterone excretion (U-Aldo) and fractional excretion of filtered K (FEK) were examined in 69 healthy children aged 12 to 15 years to assess the relationship between the sodium pump receptor in erythrocytes and the renal handling of potassium (K). Bmax showed a signifi-cant negative correlation with FEK. Subsequently, FEK showed a negative correlation with serum K which was within normal range in every child, and a positive correlation with U-Aldo. However, Bmax showed no correlation with serum K or U-Aldo. These findings suggest that aldosterone may influence Bmax via the changes in FEK and serum K within physiological ranges. In other words, there can exist a close relation between Bmax and the renin-angiotensin-aldosterone sytem through K metabolism.

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Recent studies indicate the important roles of mesangial cell dysfunction and insulin-like growth factor I (IGF-I) in the development of diabetic nephropathy. In order to know whether hyperglycemia could alter IGF-I action on mesangial cells, we examined mitogenic and metabolic effects of IGF-I on mesangial cells. Mesangial cells revealed to express considerable numbers of receptors specific to IGF-I will relatively small numbers of insulin receptors. The uptake of [₃H]-2-deoxy-glucose, [₃H]-aminoisobutyric acid (AIB), or [₃H]-thymidine into mesangial cells was stimulated by IGF-I at physiological concentrations. Under high concentrations of glucose (55 mM), the stimulation of thymidine uptake by IGF-I was significantly suppressed from 5863±549 (at 11 mM glucose) to 1731±146 DPM/100μg/prot. On the contrary, AIB incorporation by IGF-I was significantly enhanced in the cells cultured under high concentration of glucose, as 2.03±0.03 n mol/mg protein/ 15 min at 55 mM glucose vs 0.59±0.01 at 11 mM glucose. In conclusion ; 1) IGF-I had metabolic and mitogenic effects on rat mesangial cells at physiological concentrations. 2) under excess glucose conditions, mitogenic action of IGF-I on rat mesangial cells was suppressed, while amino acid incorporation was enhanced. These results suggest that modulation of IGF-I effects on mesangial cell by glucose could be associated with mesangial cell dysfunction in diabetes.

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Sixty-one patients with idiopathic membranous nephropathy (MN) were studied clinicopathologically to determine the significance of focal glomerular sclerotic lesions (FGSL) . Renal biopsy specimens were examined by light and immunofluorescence microscopy. The light microscopic specimens were cut into 20 serial sections and odd-numbered ones were stained with Masson trichrome staining. The histopathological findings were scored and statistically analyzed. The patients were divided into two groups : Group I consisted of 15 MN patients with FGSL ; the other 46 MN patients without FGSL composed Group II . Group I showed higher systolic blood pressure (p<0.01), longer duration of proteinuria (0.05), and higher levels of serum creatinine (p<0.001) than Group II. In Group I, the stage of membranous lesions was more advanced (p<0.01), and tubular atrophy, interstitial fibrosis and arterio-losclerosis were more severe than in Group II (p<0.05) . The above results suggest that FGSL in MN may be related to the impairment of the renal function, but an only explanation for the cause of FGSL by the glomerular hyper-filtration theory is unlikely. Further investigations are required to clarify the full pathogenesis of FGSL.

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We analyzed clinicopathologic characteristics of adult-onset membranoproliferative glomerulonephritis (MPGN) by comparing two tentatively-classified subgroups. Group A consisted of 9 patients in whom more than 50% of glomeruli showed mixed segmental and global duplication of glomerular basement membrane (GBM), and Group B 9 patients with global duplication of GBM. Group A showed a tendency for more favorable clinical course and outcome than Group B. Nephrotic syndrome was present in 33% of Group A and 100% in Group B, hypertension in 22% and 44%, hypocomplementemia in 44% and 67% at the time of renal biopsy. Deterioration of renal function, at comparable durations of follow-up of 62±12 (M±SE) and 53±13 months, was observed in 22% of Group A and 56% in Group B, respectively. Histologically, mesangial proliferation and tubulointerstitial change were more pronounced and frequency of sclerosing glomeruli was greater in Group B. There was also a negative correlation between the extent of global double contour and renal function as assessed by creatinine clearance at the time of renal biopsy (r=-0.55, P<0.05). These results indicate that the high incidence of global double contour, in addition to the presence of marked tubulointerstitial change and sclerosing glomeruli, may relate to progressive deterioration of renal function in MPGN. That outcomes for Group A and Group B may be different when clinical parameters, including the durations from onset of symptoms to the time of biopsy and lenght of follow-up periods, are comparable also indicates that these two groups should be considered separate entities, at least on the basis of clinical results.

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It has been reported that minimal change nephrotic syndrome (MCNS) shows no deposit of immunoglobulins or complement components in the glomeruli. We found 6 patients with IgA deposits in the glomeruli among 101 patients with MCNS, and examined the clinicopathological features of these cases. In all cases, light microscopy showed minor glomerular abnormalities. However, immunohistochemical study demonstrated marked IgA deposits in the glomerular mesangium. IgM was detected in 5 cases, IgG in 2, C3 in 2, and Clq in 1. On electron microscopy, small mesangial deposits were found in all cases and foot process effacement was partially demonstrated. There were no abnormalities in the glomerular basement membrane. The renal functions were within normal ranges in all 6 cases. In three cases, biopsies were performed within a month after the initiation of profuse proteinuria. In the other three cases, frequent relapses had been observed for 6 to 15 years before the biopsies. However, all patients ultimately revealed complete remission with corticosteroid treatment. Serum IgA levels were within normal range in examined 4 cases. Hematuria was negative in all of them. The clinical findings seem to be identical to MCNS rather than IgA nephropathy, and IgA deposits may have no pathogenetic significance, although the pattern of deposition looks quite similar to that of IgA nephropathy. These results indicate that the renal lesions in the 6 patients may belong to the subtype of MCNS, rather than IgA nephropathy.

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In order to evaluate an inhibitory effect of Al on haem synthesis, erythrocyte uro-porphyrinogen-1-synthetase (RBC-Uro-S) activity and erythrocyte level of protoporphyrin (RBC-protoporph) were measured and compared with RBC-Al in 22 patients on maintenance hemodialysis. RBC-Uro-S activity was varied from 38 to 83 nM/ml RBC/hr 37°C (54.18±12.42 nM/ml RBC/hr 37°C) and a slight elevation could be found no more than in two cases. On the other hand, RBC-protoporph levels showed to be significantly elevated in many cases such as 8 cases out of 22 (36.4%). (normal subjects: 63.25±27.61 μg/dl RBC, HD patients: 90.0+28.35, μg/dl RBC). This study failed to confirm a significant negative correlation between RBC-Al and RBC-Uro-S activity, but a positive significant correlation could be found between RBC-Al and protoporphyrin levels. However we could confirm a negative correlation neither between RBC-Al and Hb values nor between RBC-Uro-S activity and Hb values. Therefore we concluded that Al-intoxication in the patients on long term hemodialysis had a definite inhibitory effect on heme synthesis, but it was by no means a major factor in pathogenesis of anemia associated with chronic dialysis.

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A 19-year-old female patient with renovascular hypertension accompanied by focal segmental glomerulosclerosis like lesion in the contralateral kidney is described. She was admitted to our hospital for uncontrollable hypertension which was first pointed out at check-up when she was 18 years old. On admission physical examination revealed remarkable hypertension and a bruit around the umbilical region. Laboratory findings disclosed renal dysfunction and slight proteinuria (0.8-1.1 g/day). Arteriography revealed severe narrowing of the right renal artery suggesting fibromuscular dysplasia. Taken together, renovascular hypertension was diagnosed. She underwent an operation to reconstruct the artery with autotransplantation of the ipsilateral kidney in the pelvic cavity, and sections were taken from both kidney for histological evaluation during the procedure. After the operation her blood pressure normalized and proteinuria decreased. And interestingly, the kidney specimens revealed that the left side consisted of focal segmental glomerulosclerosis like lesion whereas the right was only of ischemic change. Hyperfiltration theory has recently been highlighted experimentally. And the etiology of the renal findings in this case may be based on such hemodynamic alteration as has been described in animal models. We present the case so that it may be of some help to understand how focal segmental glomerulosclerosis is brought about in humans.

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This report concerns two boys with minimal change nephrotic syndrome progressed to renal failure. The first case aged 17 being a steroid sensitive infrequent relapser developed acute renal failure at his third relapse and recovered soon after the treatment with diuretics and corticosteroids. The second case aged 15 being a steroid dependent frequent relapser became steroid resistant at his 11th relapse and progressed to renal failure seven months later. As the causes of renal failure, acute tubular necrosis and tubular obstruction by casts were suspected in the former. Renal vein thrombosis, morphological transition of renal histology, hemodynamic change and change in glomerular permeability might be occurred in the latter. Renal failure is a rare complication of minimal change nephrotic syndrome and the cause is variable. Precise diagnosis and prompt treatment should be needed to improve the prognosis.

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Naturally occurring swine glomerulopathy was investigated and its glomerular tissure injury was compared with that of human IgA nephropathy. Mild proteinuria (30%) and microhematuria (17%) was found in 30 six-month-old swine. Serum creatinine level was 1.8±0.4 (mean±SD) mg/dl, Light microscopy (LM) disclosed diffuse or focal glomerulopathy with mesangial enlargement and hemispherical deposits in six-month-old swine. Erectron microscopy revealed dense deposits in the mesangial, paramesangial and subendo-therial areas. On immunofluorescense (IF) staining findings, granular deposits of IgA (97%), IgG (97%), IgM (80%), C3 (100%), and mycoplasma hyorhinis (MB) antigen(90%) were found in the mesangial areas and along the capillary walls. One three-month-old pig and one five-year-old Goettingen mini pig were also found to have granular deposits of immunoglobulin and MH antigen in the glomerulas. In contract, no glomerular lesion was found in all 4 new-born pigs and 4 fetal pigs by LM and IF study. In six-month-old swine anti-nuclear factor and anti-DNA antibody were negative, and no pathological lesion was found in the liver by LM. And IgA and MB antigen containing circuling immune complexes were positive in sera by Raji cell assay, and moreover IgA and MH antigen was found codepositing by the double stain techniques. These findings suggest that swine glomerulopathy is similar in appearance to human IgA nephropathy and MB antigen may contribute to the development of this nephropathy.

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The purpose of this study was to investigate the changes in scavenging enzymes activities of reactive oxygen species (ROS) in experimental nephritis and nephrosis. Anti-GBM nephritis was induced in rat by injecting 0.75ml of the anti-GBM serum. Intrarenal SOD-like activity in nephritic rats was significantly decreased from the 5th day after i. v. injection of antiserum to the 10th day. Although catalase and glutathione peroxidase activities in nephritic rat were increased on 3hr to 6hr after i. v. injection of antiserum, the both activities were grandual decreased on 24hr onward. The decrease in ROS scavenging enzymes activities paralleled with the urinary protein excretion and the elevation of plasma lipid peroxide. Moreover, catalase, administered (4, 600 U/hr) by osmotic minipump prevented the urinary protein excretion by about 60%. In accelarated passive Heymann nephritis and puromycin aminonucleoside nephrosis in rats, the activities of scavenging enzymes decreased in the course of experimental periods. It was concluded that the scavenging enzymes activities of ROS increased at beginning of heterologous phase and decreased at the end of this phase in anti-GBM nephritis, and the activies in the other models of experimental nephritis also decreased during experimental periods.

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Studies were performed on the platelet aggregation (PA) in patients with chronic renal failure (CRF) and normal subjects (NS). The PA was invesigated in the whole blood by the electrical impedance method. The concentrations of plasma (P-) and erythrocyte (E-) guanidinosuccinicacid (GSA) and methylguanidine (MG) in uremic patients with CRF were determined by high performance liquid chromatography. GSA and MG are guanidino compounds (GC) and have been widely shown to act as uremic toxins. The effects of GSA and/or MG on the PA of NS were also investigated. The results showed that the PA of conservative therapy patients with CRF was significantly lower than that of NS, while the PA of hemodialysis (HD) patients was improved. The PA of continuous ambulatory peritoneal dialysis (CAPD) patients was rather high and the possibility of sugar and lipid metabolic disorders was suggested as the cause. The concentrations of P-and E-GSA and MG in uremic patients with CRF were increased. But there were no significant correlations between the PA and the concentrations of GSA and MG. In vitro, GSA and/or MG at a high concentration exerted a significant inhibitory effect, while at a low concentration they showed a lesser inhibitory effect on the PA. In conclusion, based on their inhibition of the PA in patients with CRF, the dialyzable materials, GSA and MG, are considered to represent active uremic toxins.

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The effect of metabolic acidosis (MA) on amino acid and keto acid metabolism was studied in fourteen patients with chronic renal failure (CRF) under the low protein diet (0.6-0.8g/kgBW). The comparative study of five patients with renal tubular acidosis was carried out. Each patient was investigated before [MA(+)period] and after correction with sodium bicarbonate administration lasting 10 days [MA(-)period]. The correction of MA improved nitrogen balance and elevated plasma branched-chain amino acids (BCAA), keto acids (BCKA), glutamine and alanine concentrations. No effect was however, observed in change of plasma insulin and glucagon. Oral administration of the keto-analogues of BCKA [0.1 g/kgBW of alpha-ketoisovaleic acid (KIV) and alpha-ketoisocaproic acid (KIC) ]is made for the purpose of investigating the change in the metabolic conversion rate to amino acids. As a result, MA(+)suppressed an increase in plasma KIV and KIC concentrations. Moreover, an increase in plasma valine and leucine concentrations were suppressed by MA (+). These results suggested that MA stimulates BCKA oxidation and suppresses the protein sparing effect of leucine and KIC, and accelerates the catabolism in CRF under the low protein diet. The correction of MA is ineffective in severe renal failure (serum creatinine above 10.0mg/dl), because the other uremic factors appear to be affecting protein and amino acid metabolism. Therefore, it might be concluded that MA should be corrected at an earlier stage of CRF.

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