This study was undertaken to analyze the mechanisms of immune complex formation in Heymann nephritis. We isolated two different RTE antigens by gel filtration and prepared rabbit antisera against these antigens. By the indirect immunoflurescence method using normal rat renal tissues, the 65, 000 molecular weight antigen (=β) was observed not only in RTE, but also in the glomerular epithelium, epithelium of the small intestine, liver and spleen. On the other hand, the 35, 000 molecular weight antigen (=γ) existed in RTE and epithelium of the small intestine. When rats were injected intravenously with rabbit antiserum against β, glomerular depositions were observed within two hours. In rats injected with rabbit antiserum against r, no glomerular deposition was seen with-in 2 days, but fine granular depositions were observed after 6 days. When rat kidneys were perfused with rabbit antiserum against γ in saline by a single pass method, no glomerular deposition was seen. However, in rat kidneys perfused with preformed soluble γ-anti γ IC, fine granular depositions along the capillary walls were seen soon after the perfusion. Further the antigen which was reacted with anti γ antiserum was isolated from normal rat serum by immuno-affinity chromatography. These facts suggest that the mechanisms of IC formation may be due to not only in situ immune complex formation but also circulating immune complex deposition in Heymann nephritis.

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In order to analyze the antigens (Ags) which cause Heymann nephritis (HN) and mechanisms of IC formation in the subepithelial site of GBM, we isolated two Ags from renal tubular epithelium (RTE) from Wistar rats and prepared rabbit antiserum against these Ags. Classical HN was induced by immunization with crude renal tissue suspension by the method of Heymann et al.. Immunofluorescence method in normal rat kidney revealed that the Ag with MW of 65KD (=β) existed not only in RTE, but also in the glomerular capillary wall. On the other hand, the Ag with MW of 35KD (=γ) only existed in RTE. Circulating Abs and glomerular eluted Abs from the kidney of classical HN, reacted to RTE only by indirect immunofluorescence. Soluble Fx1A, β and γ were electrophoresed on SDS-PAGE gels and transblotted onto nitrocellulose membrane, anti jl Abs reacted to several bands including 330KD band of Fx1A and β Ag. However anti γ Abs reacted to only 330KD band of Fx1A and γ Ags. On the other hand, Glomerular eluted Abs from the kidney of classical HN reacted to several bands of Fx1A and r Ag, but not to β Ag. These facts suggest that β and γ are components of 330KD protein of Fx1A. The γ Ag is thought to be one of of the major pathogenic Ag in HN.

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In situ immune complex glomerulonephritis can be induced in the rat employing cationized antigen planted in the glomerular basement membrane (GBM) as a target for specific antibody. Another possible mechanism of in situ immune complex formation is antibody already present in the GBM to bind circulating antigen. Present study was performed in order to determine whether cationized antibodies planted in the GBM could react with anionic as well as cationic antigens to form immune deposits. Horse ferritin, rabbit antibody to horse native ferritin (f-Ab) and rabbit antibody to ovalbumin (o-Ab) were highly cationized as described by Danon et al. The ability of the cationized antibodies to precipitate antigens was estimated by Ouchterlony analysis. 500μg/100g body weight (b. w.) of cationized f-Ab or o-Ab was perfused into the left renal artery of male Wistar rats and 0.1-10.0 mg/100 gb. w. of either native or cationized ferritin or ovalbumin was injected respectively into the tail vein 1 hr later. Estimation of proteinuria was done and the kidneys were removed up to 5 days for immunohistological as well as electron microscopical examination. Cationized antibodies bound to anionic sites of the GBM and combined with subsequently injected cationized ferritin or native ovalbumin in situ, both leading to formation of subepithelial immune deposit with activation of C3 and caused mild proteinuria. Native ferritin, however, induced neither subepithelial immune deposit nor proteinuria, because it didn't permeate through the GBM. The presented model indicates that antibody molecules of high positive charge can bind to the GBM and react with specific antigens that are traversing the barrier to form immune deposits. This is independent of the charge of antigen provided that the antigen molecules are permeable into the GBM, as is the case with ovalbumin but not native ferritin.

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The case of IgA glomerulonephritis that shows minimal change with nephrotic syn-drome is unusual. Thirteen patients of mesangial IgA deposition of minimal change with nephrotic syndrome (IgAMCNS) are discussed in comparison with twenty patients of non IgA deposition of minimal change with nephrotic syndrome (MCNS). On a common basis of hematuria, two groups are undistinguished. On a reaction pattern to steroid treatment, the former is based on IgA nephritis and the latter is based on minimal change with nephrotic syndrome. There is no difference in light microscopical findings between the two groups. Electron microscopically, the former suggests IgA nephritis and the latter suggests minimal change with nephrotic syndrome. In immunofluorescense, the former group is rare to show typical IgA glomerulonephritis. In conclusion, IgAMCNS is considered to be nephrotic syndrome with asymptomatic IgA deposit in mesangium.

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To clarify the ultrastructural changes of renal proximal tubulus in initial nephropathy having microalbuminuria, we observed 80 biopsies of non-insulin-dependent diabetics by light and electron microscopically morphometric analysis. The patients were divided into four groups; group I; no proteinuria (p. u.) & normal serum creatinine (Cr.); less than 1.5 mg/dl, group II; p.u.<0.5 g/day & normal Cr., group III; p.u.>0.5 g/day & normal Cr., group IV; Cr.>1.5 mg/dl. Age-mached 20 normal patients and 40 patients with IgA-nephropathy (20 cases with Cr.≤1.5 mg/dl, 20 cases with Cr.>1.5 mg/dl) were used as controls. In diabetics in Group I and II, significant changes were as follow. 1) general mitochondrial enlargement in size in proximal tubular cells, and significantly related to the level of fasting blood glucose, 2) enlargement of proximal tubular cells and their nuclei in size, 3) thickening of the proximal tubular basement membrane, and in group I, it indicated to get worse in future, 4) no relationship between the mitochondrial enlargement and other parenchymal parameters such as glomerular sclerotic change, interstitial fibrosis, luminar narrowing of arterioles and prognosis. Glomerular nodular-lesion, glomerular sclerotic change, and cortical tubulointerstitial fibrosis were only appeared in the advanced stages ; Group III and IV. We concluded that mitochondrial enlargement could be caused the initially urinary excretion of low molecular proteins and microalbumine in diabetics, probably due to disturbances of ATP synthesis, reduction of active transport, and finally decreased of reabsorption in the proximal tubulus.

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Anti-neutropil cytoplasmic antibodies (ANCA) have been found in patients with systemic vasculitis and crescentic glomerulonephritis. Recently two types of ANCA were identified, one is anti-myeloperoxidase antibodies (Anti-MPO Ab) stained perinuclear pattern of alcohol-fixed neutrophils by immunofluorescence test, and the other is autoantibodies with no reactivity with myeloperoxidase stained diffuse cytoplasmic pattern (C-ANCA). We investigated 59 patients with various glomerulonephritis with or without crescent to detect anti-MPO Ab and C-ANCA by an enzyme-linked immunosorbent assay. The results were as follows: 1) Anti-MPO Ab were detected only in patients with various glomerulonephritis with crescent. 2) Titers of anti-MPO Ab were high related to percentage of crescent in some cases of glomerulonephritis. 3) Titers of anti-MPO Ab were elevated at stage of cellular and fibro-cellular crescent. 4) C-ANCA were detected only in patients with Wegener's granulomatosis. These data suggested that anti-MPO Ab may play important roles in crescent forma-tion and may be a marker of crescent formation in various glomerulonephritis.

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Detailed histopathological study were performed and compared with clinical features in 120 children with serial renal biopsies who were found by school screening program. 41 cases (34.2%) of IgA nephropathy (IgAN), 26 cases (21.7%) of thin membrane disease (TMD) and 22 cases (18.3%) of normal glomeruli ([Normal]) accounted for 74.2% of all biopsies. 81 cases (67.5%) were revealed to be minor glomerular abnormalities by light microscopy and which contained 26 cases (32.1%) of TMD, 22 cases (27.2%) of [Normal] and 19 cases (23.4%) of IgAN. The frequency and the severity of proteinuria was significantly higher in IgAN than in TMD and [Normal] (P<0.01, P<0.05). Hematuria was significantly greater in [Normal] than in IgAN. In the 71 follow-up cases, no patient went to renal insufficiency, moreover, urinary abnormalities had disappeared in 25.4% of the patients including IgAN, TMD, [Normal], nonIgA proliferative glomerulonephritis, incomplete foot process disease and MPGN. [Normall] consisted of stationary or exercised urinary abnormality.

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We measured the activity of urinary lipase by high sensitive photometric method using 1, 2-dirinoleoilglycerol as a substrate. Also, we investigated the clinical significance of the activity of urinary lipase in patients with chronic glomerulonephritis (GN) with special reference to the relation between the levels of the enzyme and histopathological changes of the kidney. Urinary activity of N-acetyl-β-D-glucosaminidase (NAG) and urinary β₂-microglobulin (BMG) were also measured to compare the difference of renal handling of these 3 substances. We could obtain the following results; 1) Good coefficient of correlation was observed between the activity of urinary lipase and the excretion of urinary BMG. 2) No correla-tion was observed between the activity of urinary lipase and the amount of urinary NAG in patients with chronic GN. 3) In some of the cases with secondary tubulointerstitial edema and inflammatory infiltration, the values of the activity of urinary lipase were markedly elevated. These results suggested that lipase was removed from the serum mainly by glomerular filtration and reabsorbed almost completely by tubular epithelial cells like the renal handling of BMG. In contrast, NAG secreted through the different renal metabolism in proximal tubule. The activity of urinary lipase might be a diagnostic marker for the secondary acute tubulointerstitial lesions in patients with chronic GN.

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To evaluate the effects of correction of anemia with recombinant human erythropoietin (r-HuEPO) on the hemostatic defects in uremia, hemostatic parameters were examined in 18 patients with renal anemia receiving hemodialysis (HD). During the study, hematocrit (Ht) increased from 22.9±3.1% (mean±SD) at pre-treatment (stage-I) to 31.0±3.0% 12 weeks after 3000IU intravenous r-HuEPO administration at the end of every HD (stage-II), and decreased to 26.2±4.2% 6 weeks after r-HuEPO discontinuation (stage III). Platelet count did not change among these three stages, however, mean platelet volume significantly increased at stage II compared to stage I. Ivy bleeding time (Ivy-BT) significantly shortened at stage II (I; 14.3±6.0, II : 10.1 +6.5 min, p<0.01), and prolonged again at stage III (p<0.05 vs stage II). Among the patients, 6 out of 18 patients did not show any reduction in Ivy-BT (unchanged group). Though there were no significant changes in platelet aggregation rates, plasma TxB₂, 6-keto-PGF_1α, F. VIII : C, and F. VIII: Ag levels throughout the study, platelet adhesion rate was significantly improved at stage II (I; 11.8±6.8, II; 19.6±12.8%, p<0.05), and similar augmentation in vWf : Ag was observed. Improvement in these two parameters were more remarkable in shortened Ivy-BT group (n=12) than in unchanged group. From these results, we conclude that the correction of anemia with r-HuEPO in HD patients brought about the improvement in uremic bleeding tendency via the increases in red blood cell volume and newly production of platelet, which reflected improvement in platelet adhesion, and the increase in vWf : Ag.

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The effect of pulse therapy on severe secondary hyperparathyroidism related to chronic renal failure has been examined in 11 patients on maintenance hemodialysis by using an oral administration of 8μg of 1α (OH)D maximum per week. Throughout the 10 months of this treatment, the serum levels of intact-PTH, HS-PTH, and C-PTH were followed up. Addditionally, to estimate the peak level of 1, 25(OH)₂D, its serum concentra-tion at 10 hours after the 1α (OH)₂D ingestion was measured. Results have shown that the serum levels of the intact-PTH, HS-PTH, and C-PTH were lowered in 9 of these 11 patients, two of this number especially showing a marked suppression of the serum intact-PTH to a low that was near to the normal upper limit level. In the two other cases of these 11 patients, no suppression was seen in any of serum PTH levels throughout the 10 months. In the cases that showed a good response, the 1, 25(OH)₂D serum concentration elevated significantly, to more than 100 pg/ml at 10 hours after the la (OH) D intake. In contrast, in the 2 cases that showed no pesponse, no appreciable elevation in the serum concentrations was noted. Thus, since the pulse therapy using 1α (OH) D decreased the serum levels of the intact-PTH, HS-PTH, and C-PTH in 9 out of the 11 cases, we have concluded that pulse therapy using 1α (OH) D is a valid therapy for secondary hyperparathyroidism in patients on maintenance hemodialysis.

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A 74-year-old man was admitted to our hospital because of a treatment for his right renal tumor. The abdominal CT scanning revealed a mass in the right kidney, and a right selective renal arteriography demonstrated a hypervascular tumor. On admission, urinalysis revealed proteinuria (3-4 g/day) and microscopic hematuria, and serum electrolytes were normal. Serum creatinine and urea nitrogen levels were 1.6 mg/dl and 30 mg/dl, respectively. A percutaneous right renal biopsy specimens showed crescentic glomerulonephritis. Direct immunofluorescence studies showed strong linear staining for IgG and IgA along the glomerular capillary walls. Electron microscopy showed increased mesangial matrix and swollen epitherial cells, but no dense deposits in the paramesangial area and in the glomerular basement membrane. The patient underwent right radical nephrectomy. Histologic examination of the resected specimen revealed renal cell carcinoma. Postoperatively, he developed rapidly progressive renal failure and the renal function could not be recovered. Using the indirect immunofluorescence technique, we could not confirm the presence of a serum anti-glomerular basement membrane antibody, although the examination could not be carried out until the initiation of hemodialysis therapy. Some cases of glomerulopathies associated with renal cell carcinoma were previously reported, but the case of crescentic glomerulonephritis was very rare.

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A rare case of idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulirlemia (IPL) associated with chronic renal failure was described in this report. A 73-year-old male was admitted and diagnosed as IPL. IPL is proposed by Mori et al. in 1980. Clinical entity of IPL is (1) Polyclonal hyperimmunoglobulinemia (2) Systemic Lymphadenopathy characterized by remarkable mature plasmacytosis without atypism and by no destruction of the structures. (3) All disease with polyclonal hyperimmunoglobulinemia can be excluded. In this patient, physical findings showed enlarged lymph nodes (1-2 cm) in bilateral nuchal, submandibular, axillary and inguinal lesions. Laboratory examinations showed polyclonal hyperimmunoglobulinemia (especially IgG, IgA), anemia and renal dysfunction. Microscopic observation of hematoxylin-eosin staining in the axillary lymph node showed increased mature plasma cells without evidence of malignant growth. Immunoperoxidase staining showed intracytoplasmatic polyclonal immunoglobulins. IPL is known as invasing other organs besides lymph node, for example skin, lung or kidney. This patient showed renal dysfunction (Cr clearance 11 ml/min, severe proteinuria). Nine cases of IPL and multicentric plasma cell type Giant Lymphnode Hyperplasia (GLH) concurrent with renal dysfunction were reported. Only in two of them chronic renal failure were reported. Twice a week hemodialysis improved his condition and laboratory findings.

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Four cases of urothelial tumors diagnosed during hemodialysis were reported. Patients' ages ranged from 43 to 74 years old. One case was female and others were male. Durations of dialysis at the time of diagnosis were 13 to 24 months. Chief complaints of these four cases were gross hematuria. One case with bladder tumor underwent emergency operation because of repeated bladder tamponade. Partial cystectomy was performed on this case. Other two cases with bladder tumor were treated with endoscopic method. Simple nephrectomy was done in the case with renal pelvic tumor. Post operative course in all four cases were uneventful without major complications.

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