Detection of serum IL-6 in patients with diabetic nephropathy.
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Diabetes Mellitus, Type 2↗
Biomedical subjects
I Shirato
Publications and source records attributed to I Shirato.
Two adult cases of IgM-associated mesangial proliferative glomerulonephritis.
Two adult patients with mesangial proliferative glomerulonephritis with diffuse IgM deposition in the glomeruli are reported. Case 1 was a 25-year-old female with nephrotic syndrome who showed complete remission after treatment with prednisolone (PSL). Case 2 was a 46-year-old male with asymptomatic proteinuria who showed incomplete remission (0.5-1.0 g/24 hr) of urinary protein without any medication. In light microscopy, these patients revealed minimal or slight proliferation of glomerular mesangial cells without glomerular sclerosis and crescent formation. Deposition of IgM and C3 was observed in the glomerular mesangial areas and capillary walls by immunofluorescence. Electron-dense deposits were observed in the glomerular mesangial areas in these patients. Mesangial proliferative glomerulonephritis associated with diffuse IgM deposition in the glomeruli appears to have a benign clinical course. It has also been suggested that this disease has variant clinical courses since we recently experienced two other patients with mesangial proliferative glomerulonephritis with focal IgM deposits who showed renal tubular dysfunction or chronic renal failure.
Adult↗
A case of thin basement membrane syndrome associated with idiopathic membranous nephropathy.
A 59-year-old woman has had persistent microscopic hematuria for 10 years. A few days after the onset of upper respiratory tract infection, edema and severe proteinuria appeared. In renal biopsy, an electron micrograph revealed electron dense deposits in the subepithelial regions with diffuse thinning of the glomerular basement membrane. These glomerular findings were compatible with thin basement membrane syndrome associated with membranous nephropathy. On the basis of our review of the literature, the association of these two diseases seems to be very rare.
Basement Membrane↗
Endothelin-1 mRNA expression by peripheral blood monocytes in IgA nephropathy.
We investigated endothelin-1 mRNA expression in peripheral blood monocytes from 40 patients with IgA nephropathy, 40 with other glomerulonephritides and 10 with essential hypertension without renal diseases, and from 30 healthy age-matched controls. 95% of patients with IgA nephropathy had increased endothelin-1 mRNA expression in monocytes but little was detected from the other groups. Endothelin-1 mRNA was positively correlated with urinary protein excretion (95% CI 0.835-0.952) and histopathological findings (0.796-0.939). In 15 patients with IgA nephropathy endothelin-1 mRNA values and proteinuria decreased gradually after treatment. Endothelin-1 mRNA-expressing activated monocytes may be associated with the progression of IgA nephropathy.
Adolescent↗
Detection of activated platelets in urinary sediments by immunofluorescence using monoclonal antibody to human platelet GMP-140 in patients with IgA nephropathy.
The presence of activated platelets in the urinary sediments was studied by indirect immunofluorescence using monoclonal antigranular membrane protein (GMP)-140 antibody. GMP-140 is generally expressed on the activated-platelets and -vascular endothelial cells. The purpose of the present study was to determine if the presence of activated platelets in the urinary sediments is correlated with glomerular injuries in patients with IgA nephropathy. Fourteen patients with IgA nephropathy and 11 patients with diffuse mesangial proliferative glomerulonephritis without glomerular IgA deposition (PGN) were examined. The number of activated platelets in the urinary sediments was markedly increased in patients in the advanced stage of IgA nephropathy. The ratio of activated platelets to total platelets in the urinary sediments was also increased in such patients. It appears that the detection of activated platelets in the urinary sediments is useful in determining the degree of histological changes in IgA nephropathy.
Adult↗
Ultrastructural changes in glomerular epithelial cells in acute puromycin aminonucleoside nephrosis: a study by high-resolution scanning electron microscopy.
Ultrastructural changes in the podocytes were studied during the development of, and recovery from, acute puromycin aminonucleoside (PAN) nephrosis using high-resolution scanning electron microscopy (hrSEM) and transmission electron microscopy (TEM). In the process of development of PAN nephrosis, four types of early structural changes were observed before total loss of foot processes: formation of cytoplasmic blebs, masking of filtration clefts, flattening of foot processes, and retraction of foot processes. The masking of filtration clefts visualized by hrSEM corresponded to the multiplication of slit diaphragms and adhesion of foot processes in the TEM findings, and preceded retraction of the foot processes. Changes of podocyte configuration were produced. Recovery from this change of podocyte configuration began as islands of podocyte interdigitation, and was proceeded by expansion of the islands. During recovery, the primary processes were re-established either by retraction or perforation of the thin cytoplasm after the formation of foot processes. We conclude that loss of foot processes begins with the masking of filtration clefts. Recovery from the change in podocyte configuration begins with the formation of new foot processes.
Acute Disease↗
Widening of capillary neck and alteration of extracellular matrix ultrastructure in diabetic rat glomerulus as revealed by computer morphometry and improved tissue processing.
Morphological and morphometric studies of glomeruli were carried out in streptozotocin-induced diabetic rats using improved tissue processing and computerized morphometry. Increased mesangial matrix, occupying the enlarged diabetic mesangium, contained an abundance of dark granular material in addition to the microfibrils which were usually found in the control glomeruli. In the diabetic glomeruli, the lamina densa was thick and heterogeneous showing a dense layer both on its epithelial and endothelial aspects, and the lamina rara externa contained more fibrils than in control rats. Detailed estimation of the absolute values of the various compartments of the diabetic glomeruli by using perfusion-fixed materials and a computer-assisted digitizer revealed that the volume and surface area of the mesangium were increased more extensively than those of the capillary; the enlargement of the mesangial-capillary interface area was the most pronounced among the morphometric changes of the diabetic glomeruli; and that the moderate increase in capillary volume was associated with an increased radius. Our quantitative results showed that capillaries in the diabetic glomeruli had an extensively wider neck which may be the first sign of structural damage to the glomerular tuft.
Animals↗
Diffuse proliferative glomerulonephritis with hepatitis C virus-like particles in paramesangial dense deposits in a patient with chronic hepatitis C virus hepatitis.
A 62-year-old man with hepatitis C virus (HCV) infection developed proliferative glomerulonephritis with IgM and C3 deposits. Electron microscopy showed HCV-like particles in the paramesangial dense deposits, which are similar in shape to HCV previously described. These findings suggest HCV-related proliferative glomerulonephritis.
Chronic Disease↗
Alport syndrome diagnosed by immunofluorescence using a new monoclonal antibody.
A 14-year-old female with microscopic hematuria was admitted for a renal biopsy. She had a family history of renal disease without deafness. The findings of light microscopy and conventional immunofluorescence were normal. Electron microscopy showed a diffuse thinning of the glomerular basement membrane (GBM) with its mild splitting. Irregular thickening of GBM and glomerular small dense particles was not observed. Thin basement membrane syndrome was suspected from these findings. However, it was difficult to differentiate from Alport syndrome. Immunofluorescence analysis using the monoclonal antibody to the 28-kilodalton monomers of the noncollagenous domain of type IV collagen verified the diagnosis of heterozygous Alport syndrome.
Adolescent↗
A case of nephrotic syndrome associated with hepatic glomerulosclerosis and diabetic nephropathy.
We report here an adult case of nephrotic syndrome associated with hepatic glomerulosclerosis with the hepatitis C virus (HCV) antigen and diabetic nephropathy. To clarify the etiology of the nephrotic syndrome, we performed a renal biopsy and obtained the histological findings of hepatic glomerulosclerosis, glomerular mesangial cell proliferation and mesangial expansion. Electron dense deposits and deposits of IgA and C3 were also noted in the glomerular mesangial areas. Histological findings of diabetic nephropathy included thickening of the glomerular basement membrane and aneurysmal change of glomerular capillary walls in light microscopy. In immunofluorescence, linear staining of IgG was observed in the glomerular capillary walls, Bowman's capsules and tubular basement membranes. HCV was also detected focally in the glomerular capillary walls by immunofluorescence. Association of these two diseases has not been reported in any of the previous manuscripts that we reviewed. Thus, this patient seems to be a case of very rare association of the two diseases.
Adult↗
Immunofluorescent analysis of extracellular matrix (ECM) components in glomeruli of the hepatic glomerulosclerosis.
An immunofluorescence study was carried out to evaluate alterations in the distribution and/or intensity of extracellular matrix (ECM) components, immunoglobulins and complement (C3) in the glomeruli of 7 autopsy patients with hepatic glomerulosclerosis. As compared with the findings in normal renal tissues, an increase in type IV collagen, laminin and fibronectin was observed in expanded glomerular mesangial areas and along glomerular capillary walls. Depositions of IgA, mainly IgA1, and C3 in glomeruli were in parallel with those of the ECM components. These ECM components were markedly decreased in glomeruli showing global sclerosis. In contrast, type I collagen was observed at central portions of the sclerotic glomeruli. There was an increase in the type I collagen along Bowman's capsules, especially at the sites of capsular adhesion and crescent formation. It appears that hyperproduction and/or infiltration of glomerular ECM components and interstitial collagen is closely linked to the progression of glomerular sclerosis in patients with liver diseases.
Adult↗
ECM gene expression and its modulation by insulin in diabetic rats.
The steady-state levels of mRNA encoding for the alpha 1(IV) collagen chain, laminin B1 and B2 chains, basement membrane HSPG, and alpha 1(I) and alpha 1(III) collagen chains were examined in rat glomeruli at 4, 12, and 24 wk after injection of STZ. The mRNA levels for the alpha 1(IV) collagen chain, laminin B1 and B2 chains, and alpha 1(I) and alpha 1(III) collagen chains increased significantly with age in the STZ-induced diabetic rats before morphological thickening of basement membrane occurred. In contrast, the mRNA levels for HSPG decreased markedly 4 wk after STZ injection and then increased with age compared with those for control rats. The mRNA levels for these ECM components showed a continuous decline with age in controls. Treating the diabetic rats with insulin for 4 wk ameliorated the abnormally regulated ECM gene expression in the glomeruli. These data suggest that the abnormal regulation of ECM gene expression in the glomeruli may contribute to the expansion of mesangial matrix and basement membrane thickening in diabetic rats, and that hyperglycemia may play a role in the abnormal ECM gene expression.
Analysis of Variance↗
[Detection of glycosylated protein of renal tissues using NBT reaction in STZ-induced diabetic rats].
We are carried out to determine the detection of glycosylated protein of renal tissues using nitroblue tetrazolium (NBT) reaction in streptozotocin (STZ)-induced diabetic rats. The levels of glomerular non-enzymatic glycosylation were measured by thiobarbituric acid (TBA) method. There was no significant difference in the intensity of NBT in renal tissues between the 4-week diabetic rats and the same age control rats. The intensity of NBT in the glomerular mesangial areas and capillary walls was marked in 12-week diabetic rats. The staining of NBT was also observed in the tubular epithelial cells in 4- and 12-week diabetic rats. The levels of glomerular non-enzymatic glycosylated protein in 4- or 12-week diabetic rats were significantly greater than those in the same age control rats. It appears that the non-enzymatic glycosylation of renal tissues increased in the early stage of diabetic nephropathy, i.e. 4- or 12-week diabetic rats. It is concluded that the non-enzymatic glycosylation may play an important role in the initiation of renal injuries in diabetic nephropathy.
Animals↗
Increased remission of early stage membranous nephropathy on long-term treatment with corticosteroid.
Sixty-five patients with primary membranous nephropathy were examined in order to assess the effects of long-term treatment with corticosteroid. The observation period varied from 8 to 279 months (average, 95 months). The patients were treated with corticosteroid alone or with combinations of corticosteroid and immunosuppressants, nonsteroidal anti-inflammatory drugs (NSAID) and/or dipyridamole. At 6 months after treatment, only 14% of the patients had achieved complete remission. At 24 months after treatment, 46% of the patients showed complete remission. The rate of clinical remission, i.e. complete and incomplete remission, was markedly increased in stage I and II patients with membranous nephropathy by Ehrenreich and Churg's classification but not in stage III patients. The actuarial survival curve indicated that 84% of the patients were alive at 10 years after onset. These data suggest that active treatment with corticosteroid is beneficial for patients with primary membranous nephropathy.
Adolescent↗
Altered steady-state levels of mRNA coding for extracellular matrices in renal tissues of ddY mice, an animal model for IgA nephropathy.
Correlations between the steady-state mRNA levels of extracellular matrices using specific cDNA probes for the alpha 1 chain of type IV collagen (alpha 1 (IV) chain); laminin A, B1, and B2 chains; and heparan sulfate proteoglycan (HSPG); and glomerular injuries in ddY mice were evaluated. Eight-, sixteen- and forty-week-old ddY mice were used in this study. ICR mice of the same age served as control. Extracted total RNA of pooled kidneys was fixed on a filter and then hybridized with the cDNA probes. Renal cryostat sections were incubated with rabbit anti-mouse type IV collagen, laminin, and HSPG antisera and then stained with FITC-labeled goat anti-rabbit IgG antiserum. The sections were also stained with FITC-labeled goat anti-mouse IgA, IgM, IgG, and C3 antisera. In light microscopy, the average number of glomerular cells was calculated at each age. Increased expression of extracellular matrices genes for the alpha 1(IV) chain; laminin A, B1, and B2 chains; and HSPG was found in renal tissues of ddY mice. Staining of type IV collagen, laminin, and HSPG was observed in renal tissues of ddY mice at each age. Increased proteinuria in 40-week-old ddY mice might be related to the decrease in glomerular basement membrane HSPG which acts as the anionic sites in such areas. Marked proliferation and or expansion of glomerular cells and mesangial matrices were observed in 40 week-old-ddY mice. The intensity of IgA and C3 deposits in the glomeruli was parallel to the levels of mRNA for such components.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Fine structure of the glomerular basement membrane of the rat kidney visualized by high-resolution scanning electron microscopy.
The fine structure of the glomerular basement membrane (GBM) of the rat kidney was studied by means of high resolution scanning electron microscopy. Specimens were taken from kidneys perfused with paraformaldehyde, freeze-fractured and then processed with conductive staining. The fractured surface of glomerular tufts exhibited the inner and outer surface of the GBM uncovered by endothelial and epithelial cells. The lamina densa was composed of densely packed granular material together with scattered fibrils. The laminae rarae interna and externa were composed of a meshwork that showed some structural heterogeneities. The meshwork composing the lamina rara interna contained 5- to 9-nm-thick fibrils, had pores 11-30 nm wide, and was associated with granular material except in those places that corresponded with endothelial fenestrae. The meshwork of the lamina rara externa was made up of 6- to 11-nm-thick fibrils, and had smaller pores under the foot processes (10-24 nm wide) than those near the filtration slits (16-32 nm wide). In addition to the meshwork, the lamina rara interna contained microfibrils that were arranged differently depending on the topography of the capillary wall: scattered fibrils had no predominant orientation at the convex side, circumferential bundles lay at the concave side of the peripheral capillary wall, and had a circumferential arrangement in the paramesangial wall.
Animals↗
Computer imaging analysis of the correlation between intensities of glomerular immune-deposits and histopathology in patients with IgA nephropathy.
The relationship between the intensities of IgA, C3c, and C9 deposition in renal glomeruli and the severity of histopathologic injuries in patients with IgA nephropathy was examined using Microscope-Photometer 01K and a computer. Percentages of glomerular adhesion to Bowman's capsules, crescent formation, and glomerular sclerosis were calculated in the renal specimens. There was a significant correlation between the intensity of each C3c and C9 deposition in glomeruli and the degree of glomerular adhesion to Bowman's capsules and crescent formation in patients with IgA nephropathy. There was no significant correlation between the intensity of C3c or C9 deposition in glomeruli and the degree of glomerular sclerosis. No relationship was found between the intensity of IgA deposition in glomeruli and the degree of histopathologic injuries. The patients with negative or trace amounts of glomerular C3c deposits showed less severe glomerular injuries. Thus, the intensity of C3c and C9 deposition in glomeruli appears to be one of the critical factors responsible for the active progression of glomerular inflammatory process in patients with IgA nephropathy.
Complement C3c↗
Urinary levels of interleukin-6 and disease activity in patients with IgA nephropathy.
We studied, using ELISA, 27 patients with IgA nephropathy to determine if levels of urinary interleukin-6 (IL-6) might reflect the disease activity. The levels of urinary IL-6 in patients with the advanced stage were significantly higher than those in patients with the mild stage of the disease or in healthy adults. The results showed a significant correlation between the levels of urinary IL-6 and the disease activity, i.e., levels of urinary cast and urinary protein. It was thus suggested that the measurement of urinary IL-6 is useful in evaluating the degree of glomerular injuries and/or prognosis in patients with IgA nephropathy.
Adult↗