Journal of Pathology and Translational Medicine

Original Articles

IgA Nephropathy: Correlation of WHO Classification and Morphologic Semi-quantitative Scoring System.: Kyung Jin Seo, Tae Jung Kim, Kyo Young Lee, Sang In Shim, Yeong Jin Choi; Korean J Pathol. 2009;43(3):244-249.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.3.244

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BACKGROUND
IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide, and the clinical course of IgAN shows marked variability. Many efforts have made to histologically predict the clinical outcome. There are two methods to classify IgAN. One is mainly based on the glomerular changes, such as the WHO and the Lee and Haas classification systems. The other is a morphologic semi-quantitative scoring system, which counts the changes of the glomerular, tubulointerstitial and vascular structures, respectively. The purpose of this study is to determine whether the WHO classification properly reflects the various morphologic findings of IgAN.
METHODS
We analyzed 354 cases of IgAN by both the WHO classification system and the semiquantitative scoring system and evaluated the correlations of these two methods.
RESULTS
The severity of the glomerular lesions (glomerulosclerosis, capsular adhesion and mesangial matrix expansion) and the tubulointerstitial lesions (interstitial fibrosis, tubular atrophy and interstitial lymphocytic infiltration) are strongly correlated with the increase of the WHO classes of IgAN (Spearman's rho [R] > or =0.5, p<0.05). There is a weak correlation between crescent formation and the increase of the WHO classes (R=0.3, p<0.05).
CONCLUSIONS
This study shows that the WHO classification well reflects the severity of various morphologic findings and this suggests a complementary role for the semi-quantitative scoring system in classifying IgAN.

Citations

Citations to this article as recorded by

The Oxford classification as a predictor of prognosis in patients with IgA nephropathy
S. H. Kang, S. R. Choi, H. S. Park, J. Y. Lee, I. O. Sun, H. S. Hwang, B. H. Chung, C. W. Park, C. W. Yang, Y. S. Kim, Y. J. Choi, B. S. Choi
Nephrology Dialysis Transplantation.2012; 27(1): 252. CrossRef

Significance of Ultrastructural Electron Dense Deposits on Glomerular Capillary Loops in IgA Nephropathy.: Sun Hee Sung, Ok Kyung Kim, Woon Sup Han; Korean J Pathol. 1996;30(1):32-39.

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Abstract PDF: To evaluate the clinical and histopathological significance of electron dense deposits on capillary in IgA nephropathy, we reviewed and compared the clinical, laboratory, and pathological features of the patients with IgA nephropathy without loop extension of electron dense deposits(Group I, 91 cases) and IgA nephropathy with loop extension(Group II, 17cases) by ultrastructural examination using transmission electron microscope. IgA nephropathy associated with liver disease, Henoch-Schonlein purpura, systemic lupus erythematosus and the other IgA nephropathies associated with systemic diseases were excluded. The results were as follows; 1) There was no significant difference in age distribution. 2) Generalized edema was more common in group II. 3) Nephrotic ranged proteinuria(>3 g/24hr urine) was more prominent in Group II(52.9%) than Group I(8.8%). 4) Among the groups, segmental or mild deposits on the loops were noted in 13 cases, and severe and generalized deposits in 4 cases. Subendothelial deposits were noted in 6 cases, subepithelial deposits in 3 cases, subendothelial with intramembranous deposits in 1 case, subendothelial with subepithelial deposits in 1 case, intramembranous with subepithelial deposits in 2 cases, and subendothelial, subepithelial and intramembranous deposits in 4 cases. 5) The other associated ultrastructural changes of group II were diffuse effacement of foot processes with microvillous transformation, swelling or vacuolar degeneration of podocytes and glomerular endothelium. 6) According to the WHO morphologic criteria, the grade of Group II was significantly higher than Group I. From the above results, it can be concluded that the extension of electron dense deposits along the capillary loops in the cases of IgA nephropathy is highly correlated with proteinuria in the nephrotic ranged. It seems to be a poor prognostic indicator in view of the facts that it correlats with high histopathologic grading.

Immunohistochemical Study on Tenascin Expression in IgA Nephropathy.: Ho Jung Kim, Hye Jin Park, Ok Kyung Kim, Sun Hee Sung; Korean J Pathol. 2000;34(1):68-76.

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Abstract PDF: Glomerulosclerosis is a common outcome in various progressive glomerular diseases, and results from accumulation of extracellular matrices. Depending on the disease progression the extracellular matrices show quantitative and qualitative alterations. Tenascin is a significant extracellular matrix glycoprotein that expresses in normal and pathologic tissue of varying organs including kidney. We performed immunohistochemical staining for tenascin using 30 cases of renal biopsy specimens diagnosed as IgA nephropathy to study the alteration of tenascin expression in IgA nephropathy according to the histologic grading. The results were as follows; 1. The more high histologic grade, the more increase of tenascin was found in the glomerulus. 2. Tenascin was increased in proportion to the mesangial matrix. 3. The staining of tenascin was more intense in glomerular sclerotic area and was increased in proportion to the progression of sclerosis. 4. Cellular crescents showed strong positivity for tenascin. 5. Tenascin was increased in proportion to the degree of interstitial fibrosis in renal cortex. In conclusion, tenascin is an important extracellular matrix component which is significantly increased in both glomerulus and cortical interstitium according to the progress of the disease in IgA nephropathy.

Expression of Adhesion Molecules in IgA Nephropathy, Diffuse Crescentic Glomerulonephritis, and Minimal Change Disease.: Kyoung Cheol Moon, So Yeon Park, Hwal Woong Kim, Hyun Soon Lee; Korean J Pathol. 2000;34(5):331-340.

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Abstract PDF: Accumulation of leukocytes within the glomerulus is a key event in the pathogenesis of glomerulonephritis. This process is mediated by pairs of adhesion molecules. We have examined the expression pattern of selectins (E and P), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in 30 renal biopsies with IgA nephropathy, diffuse crescentic glomerulonephritis, and minimal change disease. Normal controls were obtained from four nephrectomy specimens with renal cell carcinoma. ICAM-1 expression was significantly increased in the glomerular endothelial and mesangial cells in cases with IgA nephropathy compared with normal controls. VCAM-1 was expressed in glomerular mesangial cells in all cases with IgA nephropathy and diffuse crescentic glomerulonephritis, but faintly expressed in 3 cases with minimal change disease and not expressed in normal controls. P-selectin was faintly expressed in the glomeruli in cases with IgA nephropathy and diffuse crescentic glomerulonephritis. E-selectin was only expressed in the vascular endothelium in one case with IgA nephropathy and in the other with diffuse crescentic glomerulonephritis. ICAM-1 and VCAM-1 were strongly expressed in the crescents. However, selectin was not expressed in the crescent. These results suggest that adhesion molecules, particularly ICAM-1 and VCAM-1, play an important role in the pathogenesis of glomerular damage and crescent formation in primary glomerular diseases.

Expression of Platelet-Derived Growth Factor and Extracellular Matrix in IgA Nephropathy.: Hwal Woong Kim, Kyoung Cheol Moon, So Yeon Park, Hyun Soon Lee; Korean J Pathol. 2000;34(6):446-455.

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Abstract PDF: Glomerulosclerosis represents a pathological hallmark of progressive glomerular injury. Mesangial cell proliferation and accumulation of extracellular matrix (ECM) proteins in the mesangial area frequently precede the formation of glomerulosclerosis. To understand the role of platelet-derived growth factor (PDGF) and ECM in the development of glomerulosclerosis, we examined the expression of type IV collagen, laminin, fibronectin, and PDGF in 45 renal biopsies diagnosed with IgA nephropathy (IgAN) using a standard peroxidase antiperoxidase (PAP) technique. Normal control specimens were obtained from four nephrectomy specimens diagnosed with renal cell carcinoma. As compared with normal controls, type IV collagen increased in 68%, fibronectin in 73%, laminin in 51%, and PDGF in 36% of patients with IgA nephropathy. The staining intensity of PDGF, type IV collagen, and fibronectin increased significantly in cases with moderate to severe mesangial cell proliferation than cases without. In the areas of glomerulosclerosis, the staining intensity of type IV collagen, laminin, and PDGF decreased, whereas that of fibronectin increased. These results suggest that mesangial cell proliferation in relation to increased PDGF expression in IgAN could stimulate the expression of type IV collagen, laminin and fibronectin leading to mesangial expansion. They also suggest that ECM decreased in advanced glomerulosclerosis. Deposition of fibronectin, which originates mainly from the blood stream, increases during the course of progressive glomerulosclerosis, whereas other ECM components decrease in advanced glomeruloslresosis.

Case Report

Combined IgA Nephropathy and Membranous Glomerulonephritis : A Report of Six Cases.: Ji Han Jung, Yeong Jin Choi, Yong Soo Kim, Yoon Sik Chang, Byung Kee Bang, Sang In Shim, Chang Suk Kang; Korean J Pathol. 2005;39(4):278-283.

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Abstract PDF: IgA nephropathy (IgAN) and membranous glomerulonephritis (MGN) are common in adults. However, it is unlikely that these two distinct glomerulonephrites coexist in a renal biopsy. Here, we report clinical and pathological data of six patients with concomitant existence of IgAN and MGN in renal biopsy specimens from 1990 to 2004. Five patients were male and one was female, and their ages ranged from 29 to 71 years. Four patients had microscopic hematuria, five had nephrotic range proteinuria, three had hepatitis B virus infections, three had rheumatoid factors, one had antinuclear antibodies. Two cases were developed after kidney transplant. Immunofluorescence microscopy showed characteristic findings of mesangial IgA deposits and granular IgG deposits on the capillary walls. These were confirmed by electron microscopic findings of immune-type electron-dense deposits in the mesangium and subepithelial capillary basement membranes. The pathogenesis and prognosis of the patients are discussed in this report.

Original Articles

Interstitial Mononuclear Cell Infiltration and its Phenotypes in IgA Nephropathy.: Hyeon Joo Jeong, Hyunee Yim, Sun Hee Sung, In Joon Choi; Korean J Pathol. 1994;28(5):506-510.

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Abstract PDF: To know the correlation between glomerular and tubulointerstitial lesion and to define the characteristics of interstitial inflammatory cell in IgA nephropathy and classified according to WHO classification and graded tubulointerstitial lesion as mild, moderate and severe. Paraffin-embedded 5u sections were stained with UCHL-l, L26 and CD68 antibodies. More than 20 fields were examined in each case under the high power microscopy and the number of positive cells were counted. There was positive correlation between the severity of glomerular and that of tubulointerstitial lesion. The mostcommoninflammatory cells in the interstitiuin were UCHL-l positive cells followed by CD68 and L26 positive cells. As the WHO grade or tubulointerstitial lesion increased, the numbers of positive cells were increased in all three groups. The proportion of UCHL-1 Positive cells were increased in cases with high WHO grade whereas that of L26 positive cells incases with severe tubulointerstitial lesion Proteinuria was correlated with the degree of inflammatory cell infiltration, especially with that of L26 positive cells.

IgA Nephropathy Associated with Pulmonary Tuberculosis.: Mi Kyung Kim, Hyun Soon Lee; Korean J Pathol. 1990;24(3):215-226.

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Abstract PDF: There have been a few reports suggesting that the imune response to pulmonary tuberculosis provides the appropriate setting for the development of IgA nephropathy (IgAN). To define better the relation between pulmonary tuberculosis and IgAN, we evaluated the prevalence of pulmonary tuberculosis among 386 Korean patients with IgAN. Seventeen cases (4.4%) showed abnormal chest X-ray findings suggestive of pulmonary tuberculosis. Ten patients were male and seven were female. Only one case was a child. Urinary abnormalities were detected during the course of antituberculous medication in 11 patients, and after completion of chemotherapy in 2. Chest abnormalities were noted in the remaining 4 patient after IgAN had been diagnosed. Clinical diagnosis of tuberculosis was made mainly based on the chest X-ray findings, but sputum Acid-Fast Bacilli were detected in one patient and pulmonary granulomo was noted in 2. The patients presented various clinical manifestations such as gross hematuris (5 cases), nephrotic syndrome (5 cases), asymptomatic urinary abnormalities (4 cases) and pyuris (1 case) at time of biopsy. Histologic grading of the glomerular lesions was made with modified Meadow classification (1972): one had grade I lesion, 8 grade II, 5 GRADE III and 3 showed grade IV. Follow-up studies were made in 7 patients. Six showed resolution of urinary abnormalities after completion f antituberculous medication, while one pursued chronic renal failure 20 days after the onset. The above clinical and morphologic features suggest that pulmonary tuberculosis may be partly related to the occurrence of IgAN in some Korean patients.

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