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1.
The classification of glomerulonephritis in systemic lupus erythematosus revisited 总被引:34,自引:0,他引:34
Weening JJ D'Agati VD Schwartz MM Seshan SV Alpers CE Appel GB Balow JE Bruijn JA Cook T Ferrario F Fogo AB Ginzler EM Hebert L Hill G Hill P Jennette JC Kong NC Lesavre P Lockshin M Looi LM Makino H Moura LA Nagata M;International Society of Nephrology Working Group on the Classification of Lupus Nephritis;Renal Pathology Society Working Group on the Classification of Lupus Nephritis 《Kidney international》2004,65(2):521-530
2.
Glomerulonephritis associated with hepatitis B surface antigenemia. Report of a case with features of both membranous and IgA nephropathy 总被引:1,自引:0,他引:1
A 40-year-old man with hepatitis B surface (HBs) antigenemia developed the nephrotic syndrome. Renal biopsy revealed a glomerulonephritis with features of both membranous glomerulonephropathy and IgA nephropathy. Histologically some glomeruli showed mesangial expansion and hypercellularity only, while others contained sclerotic segments. Direct immunofluorescence demonstrated granular IgG-bearing deposits along the peripheral glomerular capillaries and IgA-containing ones in the mesangium. HBs antigen was detected by indirect immunofluorescence both along the glomerular capillary walls and within the mesangium. Granular epimembranous and mesangial deposits were observed by electron microscopy. A few mesangial deposits consisted of spherical particles, 35-100 nm in diameter. Although 3 cases of mixed membranous and IgA nephropathy have been previously reported, this appears to be the first one to be associated with HBs antigenemia. 相似文献
3.
The 2003 International Society of Nephrology (ISN)/Renal Pathology Society (RPS) Classification of lupus nephritis (LN) was designed to eliminate ambiguities and standardize definitions. Major changes from the 1982 Modified WHO Classification include the elimination of the normal biopsy category and the subcategories of membranous Class V, the introduction of sharper distinctions between the classes, and the addition of subcategories within diffuse LN (class IV) for predominantly segmental (LN IV-S) and global (LN IV-G) lesions. It stipulates that sclerotic glomeruli owing to scarred LN should be taken into account when assessing the percentage of glomeruli affected by LN. Since its publication, the ISN/RPS classification has been used successfully in a number of clinical-pathologic studies. Several studies addressing the relationship between LN IV-S and LN IV-G have failed to identify a significantly worse outcome in IV-S than IV-G, although there were some differences in presenting clinical and pathologic features. Importantly, the ISN/RPS classification has achieved its goal of improved interobserver reproducibility. Its use has increased the percentage of LN biopsies meeting criteria for class IV. As it gains widespread acceptance, the ISN/RPS classification is already providing a standardized approach to renal biopsy interpretation needed to compare outcome data across centers. 相似文献
4.
K Ohta N Takano A Seno A Yachie T Miyawaki H Yokoyama N Tomosugi E Kato N Taniguchi 《Clinical nephrology》1992,38(4):185-189
Interleukin-6 (IL-6) plays a key role in inflammatory and immune responses in the host. In the present study, the IL-6 activity in urine from patients with various renal diseases was examined to elucidate the pathological and clinical significance of urinary IL-6. In patients with mesangial proliferative glomerulonephritis (mes-PGN) including, IgA nephropathy, the urinary IL-6 activity tended to increase with the progression of mesangial hypercellularity. In four patients with IgA nephropathy, urinary IL-6 activity increased markedly but transiently during episodes of acute exacerbation associated with upper respiratory tract infection. In addition, it was demonstrated that urine from patients with other types of PGN such as poststreptococcal acute glomerulonephritis and membrano-proliferative glomerulonephritis contained large quantities of IL-6. However, the levels of urinary IL-6 activity were almost within the normal range in non-proliferative glomerular diseases such as membranous nephropathy, minimal change nephrotic syndrome and lupus nephritis (WHO class I and V), non-glomerular bleeding and orthostatic proteinuria. It should be noted that a marked increase in urinary IL-6 was often observed in the patients with urinary tract infection. These results indicated that IL-6 in urine might be derived from various types of cells participating in inflammatory reactions not only in the renal parenchyma but also in the urinary tract. 相似文献
5.
BACKGROUND: The present study was undertaken to demonstrate the deposition of immunoglobulins or complements in formaldehyde-fixed and paraffin-embedded renal biopsy tissues through the unmasking of antigens with microwave treatment plus protease digestion or trypsin digestion. METHODS: Biopsy samples from patients with IgA nephritis (n = 7), lupus nephritis (7), membranous nephropathy (7) and mesangiocapillary glomerulonephritis (3) were used. Antigen unmasking was performed with (i) microwave treatment plus protease digestion for 10, 30 or 60 min, or (ii) digestion with 0.25% trypsin for 60 or 120 min. RESULTS: Microwave treatment plus protease digestion for 30 or 60 min and trypsin digestion for 120 min provided good results for the unmasking of immunoglobulins in glomeruli with structural preservation. The IgA deposits in IgA nephritis and IgG deposits in lupus nephritis and membranous nephropathy were clearly revealed in more than 80% of cases by both pretreatments. Microwave treatment plus protease digestion for 30 min revealed the deposition of C3 in all cases of mesangiocapillary glomerulonephritis and lupus nephritis and was superior to trypsin digestion. Characteristic patterns of C3 deposition were observed for these forms of glomerulonephritis, although C3 deposits in membranous nephropathy were detected in only 50% of cases. It was not possible to unmask all of the antigens in the glomeruli, especially those with weak immunofluorescence. CONCLUSION: Microwave treatment plus protease digestion is effective for the unmasking of antigens in paraffin sections and as useful for the diagnosis of immune-mediated glomerulonephritis as trypsin digestion. 相似文献
6.
BACKGROUND: Mannose-binding lectin (MBL), a member of the collectin family, binds to various oligosaccharides and activates the classical pathway of complement independent from C1q. At present it is unknown whether this so-called lectin pathway of complement activation plays a role in the pathogenesis of human glomerulonephritis. METHODS: Direct immunofluorescence of 84 renal biopsies using an MBL-specific monoclonal antibody and antibodies directed against IgG, IgA, IgM, C1q, C3, and terminal complement complex (TCC) was performed. Serum MBL levels of 50 patients were determined by enzyme-linked immunosorbent assay. RESULTS: MBL was detected in the glomeruli of patients with lupus nephropathy (15 of 16), membranous nephropathy (10/15), membranoproliferative glomerulonephritis type I (5/6) and anti-GBM nephritis (2/4). MBL deposition paralleled that of immunoglobulins, C1q, C3, and TCC but was less intense as compared to C1q. Focal segmental deposits of MBL were present in focal segmental glomerulosclerosis (4/6), IgA nephropathy (3/11), amyloidosis AL (1/4), and advanced renal fibrosis (2/2). Here MBL staining was identical to IgM and C3 and considered an unspecific entrapment of MBL in sclerotic lesions in these cases. No significant difference in MBL serum levels was observed between normal controls and patients with lupus nephritis, membranous nephropathy, membranoproliferative glomerulonephritis, focal segmental sclerosis, minimal change disease or IgA nephropathy. In patients suffering from membranous nephropathy with (n=10) or without (n=5) glomerular MBL deposits serum creatinine, C3, C4, serum protein, and proteinuria were not statistically different. CONCLUSION: MBL is present in the glomeruli of patients with glomerulonephritis involving deposition of IgG and activation of the classical pathway of complement. We propose that MBL binds to agalactosyl oligosaccharides of IgG that terminate in N-acetylglucosamine. The extent to which the lectin pathway of complement contributes to overall complement activation in the glomeruli remains unknown, but is likely to be marginal. 相似文献
7.
Suga N Miura N Uemura Y Nakamura T Morita H Banno S Imai H 《Clinical and experimental nephrology》2011,15(6):970-975
We report an unusual pathological finding, a large-sized bubbling appearance of the glomerular basement membrane (GBM), in
a patient with pulmonary limited AL amyloidosis and a past history of lupus nephritis. The first renal biopsy specimen from
10 years ago, when systemic lupus erythematosus was diagnosed, demonstrated mild mesangial proliferation and subepithelial
deposits (WHO classification: III + V). Light microscopy of the current biopsy using periodic acid methenamine silver (PAMS)
stain demonstrated a large-sized bubbling appearance of the GBM; however, very weak immunoglobulin and complement deposition
was observed in immunofluorescence studies. Routine electron microscopy demonstrated partial subendothelial expansion with
electron-lucent materials, but no electron-dense deposits or amyloid fibrils. Electron microscopy with PAMS stain revealed
electron-lucent endothelial scalloping, including some cellular components and microspheres in the GBM; however, it is not
clear if these materials are derived from endothelial cells. One possibility is that these unique findings represent a recovery
phase of lupus membranous nephritis; another is that these findings correspond to a new disease entity. 相似文献
8.
Korbet SM Schwartz MM Evans J Lewis EJ;Collaborative Study Group 《Journal of the American Society of Nephrology : JASN》2007,18(1):244-254
This study assessed whether certain clinicopathologic variables could explain the impact of race on outcome in 86 patients who had severe lupus nephritis and were available for long-term follow-up after participating in a prospective, controlled, clinical trial. Fifty-four (63%) patients were white, 21 (24%) were black, and 11 (13%) were categorized as other. The proportion of patients with anti-Ro, anti-nRNP, and anti-Sm was significantly greater among black patients. Biopsies with segmental active proliferative and necrotizing lesions that involved >or=50% of glomeruli +/- membranous glomerulonephritis (class III >or=50%+/-V) were significantly more common (white 44%, black 76%, other 36%; P < 0.05) and diffuse proliferative glomerulonephritis +/- membranous glomerulonephritis (class IV+/-V) was less common (white 54%, black 24%, other 64%) among black patients. Attainment of a remission was greatest among white patients (white 52%, black 29%, other 27%; P = 0.09). Features that were predictive of a remission were white race, baseline serum creatinine, and class IV+/-V lesions. Patient survival at 10 yr (white 81%, black 59%, other 73%; P = 0.029) and renal survival at 10 yr (white 68%, black 38%, other 61%; P = 0.015) were significantly poorer in black patients. Predictors of ESRD were serum creatinine, the presence of anti-Ro antibodies, class III >or=50%+/-V lesions, and failure to achieve a remission. In conclusion, racial differences were observed in the serologic and histologic features at presentation, response to treatment, and outcome of patients with severe lupus nephritis. In a population of patients with severe lupus nephritis, black patients were significantly more likely to have a serologic profile and renal lesions that were associated with more aggressive renal disease and resulted in worse outcomes than white patients. 相似文献
9.
Effect of methylprednisolone pulse therapy in patients with lupus nephritis assessed by WHO morphologic classification 总被引:2,自引:0,他引:2
H Makino Y Yamasaki Y Hayashi T Haramoto K Shikata I Kumagai K Taniai K Takahashi Z Ota 《Nihon Jinzo Gakkai shi》1990,32(7):791-799
To determine indications for treatment with high-dose intravenous methylprednisolone pulse therapy in lupus nephritis, we retrospectively assessed the response to pulse therapy over oral prednisolone administration in 120 biopsy proven lupus nephritis patients according to WHO morphologic classification. In the pulse group, 1 g of methylprednisolone was administered on three consecutive days and oral steroid therapy (40-30 mg) was started. In many occasions in treating class III and IV-b, repeated pulse therapy was performed. In control oral prednisolone group, middle-dose steroid therapy (50-30 mg) was started. In patients with minor glomerular abnormalities and mesangial lupus nephritis, rapid improvement of serological activities was observed in pulse group assessed by serum complement level, anti-DNA antibodies, and anti-nuclear antibodies. In patients with focal lupus nephritis, rapid rise in serum complement level and fall in proteinuria was observed in the pulse group. In patients with diffuse proliferative lupus nephritis with active necrotizing lesions, faster rise in serum complement level and proteinuria were observed in the pulse group. In patients with membranous lupus nephritis there was no significant difference between two groups. In comparison with the effect of pulse therapy among each morphologic class, the rise of serum complement level was slowest in class IV-b. Both group of IV-b and V manifested nephrotic syndrome and by pulse therapy the decrease in urinary protein was faster and more significant in class IV-b compared with class V. No significant adverse effect of methylprednisolone was observed during about 150 times of pulse therapy. Bacterial, viral infections such as herpes zoster and fungal infections were observed in pulse group as often as control group. 相似文献
10.
Glomerular localization of fibrinogen reactive antigens (FRA) and fibrinogen degradation products reactive antigens (FDP-E) was investigated in 184 renal biopsy specimens of diseased kidneys by an immunofluorescent method. There was clear dissociation of FRA and neoantigen deposits in the glomeruli in a moderately active stage of acute glomerulonephritis, chronic glomerulonephritis and in all 5 cases of lipoid nephrosis. In lupus nephritis and membranous nephropathy there were almost coincident deposits of these antigens. 相似文献
11.
Michael MENGEL Hans KREIPE Hermann HALLER Anke SCHWARZ 《Nephrology (Carlton, Vic.)》2002,7(5):262-266
SUMMARY: The case of a 48-year-old female patient who underwent renal transplantation because of an end-stage renal disease after membranous glomerulonephritis (WHO class V) in systemic lupus erythematosus (SLE) is presented. the patient lost one cadaveric allograft immediately after transplantation because of renal vein thrombosis, presumably caused by anti-Cardiolipin antibodies. A second cadaveric allograft showed a stable function for several years before slowly deteriorating. an abrupt increase of serum creatinine led to the suspicion of a final episode of acute rejection. A biopsy was performed, which showed an overlap of rejection and recurrent iupus nephritis in an advanced chronically damaged allograft. the lupus nephritis recurred as the same WHO class V as in the native kidney, but without significant predictive clinical or serological signs of SLE activity. the case presented and a review of the literature indicate that the frequency of recurrent lupus nephritis might be underestimated, and earlier surveillance biopsies in transplanted SLE patients should be considered. 相似文献
12.
Severe lupus nephritis: importance of re-evaluating the histologic classification and the approach to patient care 总被引:2,自引:0,他引:2
The histopathology of severe lupus glomerulonephritis comprises distinct patterns of injury which were initially defined by the World Health Organization Classification of 1982 as focal and segmental glomerulonephritis (category III), diffuse proliferative glomerulonephritis (category IV) and complex membranous glomerulonephritis (categories Vc, Vd). It is assumed that the morphologic abnormalities demonstrated in this classification represent distinctive differences in the mediation of the immune response which leads to a specific type of glomerular inflammation. In 1995 the World Health Organizational committee recommended a change in categorization of focal and segmental glomerulonephritis (class III) and diffuse proliferative glomerulonephritis (class IV), which would overlook the morphological differences between these categories and treat them as a continuum, recommending that biopsies classified as focal and segmental glomerulonephritis (category III) with involvement of > or =50% of glomeruli be included into the diffuse proliferative glomerulonephritis category (category IV). Since the classification of severe lupus nephritis has significant impact on prognosis and the therapeutic approach to patients with this disease, it is the purpose of this review to critically re-examine the existing classification based on new insights into differences in morphologic features and long-term outcome. 相似文献
13.
Pathological analysis of renal diseases with mild proteinuria 总被引:1,自引:0,他引:1
Ikee R Hemmi N Saigusa T Namikoshi T Yamada M Imakiire T Kikuchi Y Suzuki S Moriya H Kobayashi S Miura S 《Nihon Jinzo Gakkai shi》2002,44(8):786-791
Proteinuria is an important predictor of renal outcome in a variety of renal diseases. Proteinuria exceeding 0.5 g/day is often considered to be a major indication of renal biopsy. In this study, we analyzed the clinical and histopathological data of 58 patients with mild proteinuria of less than or equal to 0.5 g/day. The histopathological diagnosis included 45 cases(77.6%) of mesangial proliferative glomerulonephritis, 4 cases(6.9%) of lupus nephritis, one case of membranoproliferative glomerulonephritis and only 6 cases(10.3%) of minor glomerular abnormality. The percent sclerotic glomeruli exceeded 10% in 17 cases(29.3%) and reached 71.4% in 2 cases. There were no significant differences in histopathological parameters(percent sclerotic glomeruli, tubulointerstitial change, arterio-arterio sclerotic change) between the groups with or without microhematuria. There was a positive correlation between age and percent sclerotic glomeruli. Percent sclerotic glomeruli in our cases were higher than in the healthy population reported by Kaplan et al. and the influence of glomerulonephropathy was obvious. During the follow-up period(mean 19.7 months), one patient progressed to chronic renal failure and 2 patients had increased urinary protein excretion, but the others did not. These results suggest the importance of clarifying the prognosis by renal biopsy even in cases with mild proteinuria. 相似文献
14.
BACKGROUND: A recently proposed reclassification of lupus nephritis divides class IV (diffuse proliferative) lupus nephritis into those cases with predominantly segmental proliferative lesions (class IV-S) and those with predominantly global proliferative lesions (class IV-G). This report explores the validity of this distinction and possible differences in pathogenesis between the 2 types of lesions. METHODS: Patients from a previously reported series of severe lupus nephritis, with initial biopsies (Bx1) and control biopsies (Bx2) at 6 months after induction therapy were reclassified according to the newly proposed classification. From the original series of 65 patients, 15 patients were reclassified as having class IV-S lesions and 31 patients class IV-G lesions. Clinical data at both biopsies and follow-up were available on all patients selected. RESULTS: Patients with IV-G lesions had worse proteinuria, lower serum hemoglobins, lower CH50s, and likely higher SCrs (P = .06) and lower C3s (P = .08) than class IV-S patients. Serum CH50 and C3 correlated negatively with severity of class IV-G lesions, but not at all with class IV-S lesions. Patients with class IV-G lesions had greater overall immune deposits and subendothelial deposits on IF and greater hyaline deposits on light microscopy. By contrast, class IV-S showed predominant mesangial deposits and a much higher rate of glomerular fibrinoid necroses (13.3 +/- 15.3% vs. 5.6 +/- 8.0% of viable glomeruli, P = .03). Other distinctions included the fact that membranoproliferative features were found only in class IV-G lesions, and glomerular monocyte/macrophages were much more frequent in this group than in class IV-S lesions (1.77 +/- 0.92 vs. 0.86 +/- 0.77, P = .008). Finally, class IV-G frequently involved all viable glomeruli (74.2% of cases), whereas segmental proliferative lesions never did (P < .0001). Survivals from doubling of SCr at 10 years did not differ between the 2 types at Bx1: 72.5% segmental versus 60.4% global, P= .53. However, among those with persistent lesions at Bx 2 (11 IV-S and 9 IV-G), there was a dramatic difference in 10-year survivals between IV-S lesions (63.6%) and IV-G lesions (0%), P = .08. CONCLUSION: There are definite clinical and morphologic differences between class IV-S and IV-G lesions. Data suggest that class IV-G lesions behave as an immune complex disease, having positive correlations with extent of immune deposits and negative correlations with serum complement levels, the model traditionally assumed for lupus nephritis as a whole. However, in class IV-S lesions, the presence of proportionally greater glomerular fibrinoid necroses and lack of correlation with extent of immune deposits suggest that these lesions may have a different pathogenesis. 相似文献
15.
Lupus nephritis comprises a spectrum of glomerular, vascular, and tubulointerstitial lesions, which has significant racial
variation in severity and manifestations. The current classification (ISN/RPS 2003) has been improved successfully for the
categorization of lupus glomerulonephritis (LGN). On the basis of this classification, 480 Japanese cases revealed the following
distribution: class I 3%, class II 16%, class III 13%, class IV-S 11%, class IV-G 41%, class V 16%, and class VI 1%. Class
IV-G with chronicity tended to have the worst renal outcome. Nephrotic syndrome was a more frequent complication in class
IV-S (50%), class IV-G (72%), and class V (56%), with poor renal and actuarial outcomes. With regard to therapy, treatment
options including glucocorticoids alone or combined with antimetabolites (azathioprine, mizoribine, mycophenolate mofetil),
calcineurin inhibitors (cyclosporine A, tacrolimus), or alkylating agents (intravenous cyclophosphamide injection) improved
the outcome of LGN; however, there is no high-grade clinical evidence from Japan. Further studies are needed to resolve the
clinicopathological problems of LGN, especially IV-S, IV-G, and pure membranous lupus nephritis in Japanese patients. 相似文献
16.
A 15-year-old boy developed a nephrotic syndrome. At that time, autoantibodies related to systemic lupus erythematosus (SLE) had been persistently negative, even on repeated evaluation. C1q was normal, but C4, C3 and CH50 were low. Renal biopsy revealed membranous lupus nephritis (LN) based on the new classification of glomerulonephritis in SLE [Weenig et al. 2004]. We did not establish our diagnosis of SLE on the criteria of the American Rheumatism Association (ARA). The patient showed complete remission ofnephrotic syndrome treated with prednisolone and cyclophosphamide. Thereafter, he had no proteinuria and clinical evidence of SLE for 22 years. At the age of 37, however, he developed facial discoid eruption, proteinuria in the nephrotic range, hypocomplementemia and positive reaction to autoantibodies of SLE. Light microscopic findings of renal biopsy indicated mesangial LN, which showed "full-house" immunofluorescence and mesangial dense deposits associated with diffuse epithelial cell foot process effacement in electron microscopy. Steroid therapy was very effective. This case initially showed autoantibody-negative and hypocomplementemic LN with membranous type, and transformed to SLE with mesangial LN after a long interval. 相似文献
17.
P Bygren B Cederholm D Heineg?rd J Wieslander 《Nephrology, dialysis, transplantation》1989,4(4):254-261
The sera of 206 consecutive patients with biopsy-proven glomerulonephritis were tested by ELISA for the presence of Goodpasture and non-Goodpasture anti-GBM antibodies. Antigens were solubilised from human GBM with purified bacterial collagenase and with 6 mol/l guanidine-HCl respectively. Only 12 sera reacted when collagenase-resistant GBM proteins were used as antigens in ELISA. Sera from two of these patients also reacted with the Goodpasture antigen, that is the globular domain of collagen IV, purified from collagenase extracts of GBM. These two patients had classical Goodpasture syndrome with linear crescentic nephritis. The other ten sera did not react with the Goodpasture antigen and immunofluorescence microscopy showed granular glomerular immune deposits. Antibodies against antigens present in 6 mol/l guanidine-HCl extracts of human GBM were much more frequent, particularly in lupus nephritis and IgA nephropathy, but relatively common also in patients with glomerulonephritis associated with systemic connective tissue and systemic vasculitic disorders. In contrast, these non-Goodpasture antibodies were only sporadic in primary forms of glomerulonephritis such as minimal-change nephropathy, membranous glomerulopathy, or acute post-infectious glomerulonephritis. The presence of circulating IgG, IgA or IgM antibodies against 6 mol/l guanidine-HCl extractable GBM antigens correlated with granular deposits of corresponding immunoglobulins in both mesangial and capillary loop regions of glomeruli, indicating a possible pathogenic role for non-Goodpasture anti-GBM antibodies in several forms of glomerulonephritis. 相似文献
18.
Ultrastructural 'fingerprint' in cryoprecipitates and glomerular deposits: a clinicopathologic analysis of fingerprint deposits. 总被引:3,自引:0,他引:3
Cheng-Fang Su Han-Hsiang Chen Jui-Chi Yeh Shiu-Ching Chen Chuan-Chuan Liu Chin-Yuan Tzen 《Nephron》2002,90(1):37-42
Organized glomerular electron-dense deposits with a fingerprint pattern are well known in some patients of lupus nephritis or cryoglobulinemia. In general, these two diseases are always discussed separately as the causes of such deposits. However, 3 of our 5 lupus patients with glomerular fingerprint deposits also had cryoglobulinemia. One of the remaining 2 patients died and the other was lost to follow-up. The purpose of our study was to seek an appropriate clinicopathologic assessment of fingerprint deposits. All these patients showed overt proteinuria, active urinary sediment, a high degree of activity of lupus nephritis, and diffuse proliferative glomerulonephritis (WHO class IV). Their cryoprecipitates and renal biopsy specimens were investigated by means of immunochemistry, immunofluorescence and electron microscopy. The ultrastructural 'fingerprint' structures were exactly the same in the cryoprecipitates and in the glomerular deposits in 2 of 3 lupus patients with cryoglobulinemia, as were IgG, IgM and IgA. Therefore, these observations furnish emerging morphologic evidence for the glomerular deposition of immune complexes of circulating cryoglobulins in lupus nephritis. In addition, electron microscopic fingerprint deposits on renal biopsy or cryoprecipitate can be regarded as a very sensible marker of concomitant or subsequent development of diffuse lupus nephritis. If the patient is accompanied by nephritic syndrome, an early trial of immunosuppressive therapy may be warranted. 相似文献
19.
Glomerular distribution and gelatinolytic activity of matrix metalloproteinases in human glomerulonephritis. 总被引:20,自引:2,他引:18
Maki Urushihara Shoji Kagami Takashi Kuhara Toshiaki Tamaki Yasuhiro Kuroda 《Nephrology, dialysis, transplantation》2002,17(7):1189-1196
BACKGROUND: Matrix metalloproteinases (MMPs) have been implicated in the development of glomerular injury in rat experimental glomerulonephritis (GN). However, the significance of MMPs in human GN remains obscure. In order to evaluate the role of MMPs in human GN, we examined the glomerular distribution and gelatinolytic activities of MMP-2 and MMP-9 in human GN. METHODS: We performed immunohistochemistry with polyclonal anti-MMP-2 and MMP-9 antibodies, and analysed gelatin zymograms of five isolated glomeruli from various types of human renal disease. The renal specimens investigated were from normal kidneys (n=5), IgA nephritis (n=20), Henoch-Sch?nlein nephritis (n=4), non-IgA mesangial proliferative GN (n=9), lupus nephritis (n=6), acute poststreptococcal GN (APSGN) (n=4) and diabetic nephropathy (DN) (n=4). RESULTS: MMP-2 immunoreactivity was not detected in normal controls or in any type of GN. MMP-9 staining, which was almost negative in normal glomeruli, was increased mainly in the mesangial region and corresponded to the level of glomerular cell proliferative changes in mesangial proliferative GN (IgA nephritis, Henoch-Sch?nlein nephritis, non-IgA mesangial proliferative GN and lupus nephritis). Positive but weak staining for MMP-9 was observed in mesangial areas in DN. In addition, double immunostaining showed that MMP-9 is colocalized in scattered neutrophils within diseased glomeruli in APSGN. MMP-9 gelatinolytic activity in five normal glomeruli was weakly detected. Consistent with the levels of immunostaining, MMP-9 glomerular activity was dramatically increased in nephritic glomeruli with IgA nephritis, lupus nephritis and DN. The gelatinolytic activity of MMP-2 was occasionally detectable in nephritic glomeruli. CONCLUSION: These results strongly suggest that MMP-9 plays an important role in abnormal mesangial proliferative changes in human GN. 相似文献
20.
The interrelationships between tubulointerstitial immune deposits (TID), interstitial inflammation, glomerular changes, renal function, and prognosis were assessed in the renal biopsies from 93 patients with lupus nephritis. The prevalence of TID was 33% by immunofluorescence and 23% by electron microscopy. Although predominantly detected along and within tubular basement membranes, extraglomerular immune deposits were also present in the wall of renal interstitial capillaries and small arteries as well as in Bowman's capsule. The prevalence of TID correlated with the activity of glomerular lesions and, to a lesser extent, with the severity of proliferative lupus nephritis (WHO classes II-IV). TID were much less common in the membranous form (WHO class V). The severity of interstitial inflammation correlated with the degree of renal insufficiency and was an accurate prognostic indicator of progressive deterioration of renal function. However, there was no correlation between prevalence of TID and prevalence and severity of interstitial inflammation, suggesting that the latter is not necessarily secondary to the presence of immune complexes and that other pathogenetic mechanisms may be involved. 相似文献