Journal of Pathology and Translational Medicine

Original Articles

Urinary Decoy Cell Grading and Its Clinical Implications: Myoung Ju Koh, Beom Jin Lim, Songmi Noh, Yon Hee Kim, Hyeon Joo Jeong; Korean J Pathol. 2012;46(3):233-236. Published online June 22, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.233

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Background

Examination of urine for decoy cells (DCs) is a useful screening test for polyomavirus (PV) activation. We explored the significance of the amount of DCs in persistent shedding, PV nephropathy and acute rejection.

Methods

A case-controlled study was performed in 88 renal allograft patients who had DCs detected at least once in four or more urine samples.

Results

Fifty one patients were classified into the high-grade shedding group (HG) and 37 patients into the low-grade shedding group (LG) according to DC shedding (≥10 or <10 DCs/10 high power field [HPF]). DC shedding of more than three consecutive months was significantly more prevalent in the HG as compared with their LG counterparts (p<0.0001). Urinary DCs were present for more than one year in 29.4% of the HG and 8.1% of the LG. Real-time polymerase chain reaction for PV was higher in both urine (51.4% vs. 11.1%) and plasma (9.1% vs. 0%) of the HG than the LG. The prevalence of PV nephropathy was higher in the HG than the LG (p=0.019). However, there was no significant difference in the prevalence of acute rejection.

Conclusions

Shedding of ≥10 DCs/10 HPF is associated with sustained shedding, polymerase chain reaction positivity and PV nephropathy, but not a predictor of acute rejection.

Citations

Citations to this article as recorded by

Polyomavirus nephropathy: diagnosis, histologic features, and differentiation from acute rejection
Cynthia C. Nast
Clinical Transplantation and Research.2024; 38(2): 71. CrossRef
Challenges and opportunities in research on BK virus infection after renal transplantation
Yukun Tang, Zipei Wang, Dunfeng Du
International Immunopharmacology.2024; 141: 112793. CrossRef
BK Virus-Associated Nephropathy after Renal Transplantation
Yasuhito Funahashi
Pathogens.2021; 10(2): 150. CrossRef
Diagnostic utility of urine cytology in detection of decoy cells in renal transplant patients: Report of five cases and review of literature
Santosh Tummidi, Kanchan Kothari, Mona Agnihotri, Leena Naik, Amey Rojekar
Diagnostic Cytopathology.2020; 48(3): 222. CrossRef
Association of Pretransplant BK Polyomavirus Antibody Status with BK Polyomavirus Infection After Kidney Transplantation: A Prospective Cohort Pilot Study of 47 Transplant Recipients
Yu Hisadome, Hiroshi Noguchi, Yuki Nakafusa, Kukiko Sakihama, Takanori Mei, Keizo Kaku, Yasuhiro Okabe, Kosuke Masutani, Yuki Ohara, Kazuyuki Ikeda, Yoshinao Oda, Masafumi Nakamura
Transplantation Proceedings.2020; 52(6): 1762. CrossRef
Association Between the Polyomaviruses Titers and Decoy Cell Positivity Rates After Renal Transplantation
Y. Funahashi, M. Kato, T. Fujita, S. Ishida, A. Mori, M. Gotoh
Transplantation Proceedings.2016; 48(3): 921. CrossRef

Comparison of Detecting Methods of BK Virus Infection in Patients with Renal Allograft Recipients.: Sung Hak Lee, Youn Jun Park, Chul Woo Yang, Yong Soo Kim, In Sung Moon, Chang Suk Kang, Yeong Jin Choi; Korean J Pathol. 2010;44(6):636-641.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.6.636

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Abstract PDF

BACKGROUND
BK virus nephropathy (BKVN) is an emerging problem as a consequence of the use of potent immunosuppressive agents. Because optimal detection methods for the diagnosis of BKVN are required clinically, we compared the results of renal allograft biopsy, urine cytology, and urine and blood viral loads.
METHODS
Four hundred sixty two case notes from 2004 to 2009 at Seoul St. Mary's Hospital were reviewed. During that period, 286 cases of urine cytology for decoy cells, 938 cases of urine BKV reverse transcription-polymerase chain reaction (RT-PCR), and 1,029 cases of blood BKV RT-PCR were performed. All diagnostic methods were performed in 85 cases.
RESULTS
A histological diagnosis of BKVN was made in 2.4% of cases (11/462). Urine cytology for decoy cells was positive in 26.2% (75/286). BKV RT-PCR revealed viruria in positivity of 22.1% (207/938) and viremia in 5.2% (54/1,029). In cases of BKVN, the sensitivities of urine and blood BKV RT-PCR were all 100% and the specificities were 69% and 94.5%, respectively. In cases with positive urine decoy cells, the sensitivities of urine and blood BKV RT-PCR were 50% and 27.7%, with specificities of 77.7% and 100%, respectively.
CONCLUSIONS
BKV screening by RT-PCR assays may be a clinically useful noninvasive test to identify renal recipients with concurrent BKVN.

Citations

Citations to this article as recorded by

Prevalence of BK Virus among Iranian Renal Transplant Recipients: A Systematic Review and Meta-Analysis
Mohsen Ebrahimi, Alireza Mohebbi, Mohammad Mostakhdem Hashemi, Mobina Ashrafi Shahmirzadi
Journal of Clinical and Basic Research.2020; 4(4): 50. CrossRef
Asymptomatic hematuria associated with urinary polyomavirus infection in immunocompetent patients
Sung Hak Lee, Sung Hoo Hong, Ji Youl Lee, Tae Kon Hwang, Kyoung Suk Kim, Hyoungnam Lee, Yeong Jin Choi
Journal of Medical Virology.2014; 86(2): 347. CrossRef

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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Abstract PDF

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

The Morphologic Patterns of Diabetic Nephropathy in Koreans.: Si Hyong Jang, Moon Hyang Park; Korean J Pathol. 2009;43(1):36-42.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.1.36

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Abstract PDF

BACKGROUND
Diabetic nephropathy is the most common cause of end-stage renal disease and it has various pathologic features. We investigated the clinicopathologic differences between the histologic classes of diabetic nephropathy.
METHODS
A total of 46 patients with diabetic nephropathy were evaluated. Morphologically, the renal lesions were divided into three categories: class 1, diffuse or nodular glomerulosclerosis: class 2, vascular change without evidence of glomerulosclerosis: and class 3, non-diabetic renal disease superimposed on diabetic glomerulosclerosis. We evaluated the laboratory findings and the histologic findings, including mesangial expansion, interstitial fibrosis and inflammation, arteriolar hyalinosis and tubular atrophy.
RESULTS
The proportion of each class was 32 cases (70%), 4 cases (9%) and 10 cases (21%), respectively. The clinical and laboratory data showed no significant difference among the classes. For the groups of class 1, the group with nodular sclerosis showed a higher serum creatinine level than did the diffuse group (p=0.003). IgA nephropathy was the most common non-diabetic renal disease superimposed on diabetic glomerulosclerosis in our study.
CONCLUSIONS
The patients with nodular glomerulosclerosis presented with a more progressed clinicopathological features than did the patients with class 1 diffuse glomerulosclerosis. We also found 21% of all the patients with diabetic nephropathy had superimposed non-diabetic renal disease in a Korean population.

Citations

Citations to this article as recorded by

Renal biopsy pattern in diabetes mellitus patients and their correlation with clinical parameters
G. Singh, B. Naik, U. Singh, A. Modi, R. Dave
Nephrology (Saint-Petersburg).2023; 27(3): 53. CrossRef
Non-diabetic renal disease in Croatian patients with type 2 diabetes mellitus
Ivica Horvatic, Miroslav Tisljar, Patricia Kacinari, Ivana Matesic, Stela Bulimbasic, Danica Galesic Ljubanovic, Tina Katic, Darko Kristovic, Kresimir Galesic
Diabetes Research and Clinical Practice.2014; 104(3): 443. CrossRef
Clinical versus histological diagnosis of diabetic nephropathy--is renal biopsy required in type 2 diabetic patients with renal disease?
G. Biesenbach, G. Bodlaj, H. Pieringer, M. Sedlak
QJM.2011; 104(9): 771. 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 Localization of Extracellular Matrix Components in Diabetic Nephropathy.: Seung Sam Paik, Moon Hyang Park; Korean J Pathol. 1997;31(5):427-435.

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Abstract PDF: Normal human glomerular basement membrane (GBM) and mesangial matrix (MM) contain several different basement membrane components in varying degrees. The characteristic morphological and ultrastructural changes in patients with diabetic nephropathy are the thickening of the GBM and the expansion of the MM. In order to investigate the changes of extracellular matrix components in diabetes, the immunohistochemical localization was performed in 17 cases with different degrees using antisera to human collagen types I, III, IV, VI, fibronectin, and laminin. The following results were obtained: 1. The reactivity for collagen IV was increased in expanded MM in the diffuse glomerulosclerosis (GS). With the progression to the nodule formation, collagen IV was prominently decreased in the peripheral area of the nodules. 2. Collagen VI was increased in GBM and MM in the diffuse GS, it was especially prominent in the expanded MM. With the progression to nodule formation, collagen VI was prominently increased in the periphery of the nodules. 3. Interstitial collagen I and III were not stained in many of the cases with the diffuse GS. With the progression to nodule formation, these were slightly expressed. A lamellar pattern of positive reaction was noted at the periphery of the late nodular lesions. 4. Fibronectin was increased in GBM & MM in the diffuse GS, it was especially intense in the MM. With the progression to the nodule formation, the reactivity of antibody to the fibronectin was decreased. 5. Laminin was weakly stained along the GBM & trace in the MM, but was not changed in the nodular GS. In summary, the expanded mesangial matrix in the diffuse GS showed a markedly increased staining for collagen IV, fibronectin and collagen VI. Less intense linear staining for collagen VI, fibronectin, laminin, collagen IV and collagen III was noted along the GBM. In the nodular GS, the composition of the early nodules resembled that of the diffuse GS. However, the late nodular lesion of the nodular GS revealed decreased reactivity for collagen IV and fibronectin at the periphery of the nodule, where collagen VI and interstitial collagen I and III were increased in laminated pattern.

Histopathologic Analysis of the Repeated Renal Biopsies in the Course of Lupus Nephropathy.: Chong Woo Yoo, Hyun Soon Lee; Korean J Pathol. 1997;31(5):436-445.

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Abstract PDF: Lupus nephropathy shows a variable clinical course including remission, relapse and progression to renal failure. To examine the clinical or morphological parameters which might be related to the progression of lupus nephropathy, we have analyzed renal biopsies of 19 patients (M : F=5 : 14), who underwent repeated renal biopsies by morphology and morphometry. The average age of the patients was 22.8+/-9.0 years. The mean interval between two biopsies was 34.5+/-13.3 months. The first renal biopsies of these patients were diagnosed with WHO class IV (74%), class II (11%), class I (5%), class III (5%), and class V (5%). According to the clinical data the patients were divided into 3 groups, static, relapsing and progressive. At the time of the first biopsies, the amount of proteinuria in both the static and relapsing groups was significantly higher than that in the progressive group (P<0.05). The volume density of the renal cortical interstitium of the first biopsies in the progressive group was significantly greater than that in the static and relapsing groups (0.14+/-0.07 micrometer3/micrometer3 vs. 0.05+/-0.02 micrometer3/micrometer3, P<0.05; 0.14+/-0.07 micrometer3/micrometer3 vs. 0.05+/-0.04 micrometer3/micrometer3, P<0.05). The activity index of the second biopsies in the relapsing group was significantly higher than that in the static group (2.7+/-0.6 vs 1.2+/-1.0, P<0.05). In the progressive group, the percentage of glomeruli with global sclerosis and the volume density of the renal cortical interstitium in the second biopsies was elevated over the first biopsies (P<0.05). Half of the patients in the static and relapsing groups underwent a morphologic transformation on the second biopsy. However, of the 7 patients in the progressive group, only one showed a transformation from WHO class IV to class III, suggesting that the transformation is not related to the progression of lupus nephropathy. These results suggest that interstitial expansion and heavy proteinuria at the time of the first renal biopsy may bode for poor prognosis in lupus nephropathy. Furthermore, they suggest that an increased histologic activity index could be related to the relapse of the disease.

Alteration in Extracellular Matrix Components in Preeclamptic Nephropathy.: Moon Hyang Park, Seung Sam Paik; Korean J Pathol. 1998;32(3):186-192.

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Abstract PDF: The preeclamptic nephropathy is characterized by swelling of endothelial cells, interposition of mesangial cells and matrix, subendothelial deposits of incompletely defined material, and thickening of the capillary walls. To determine the distribution of extracellular matrix (ECM) components in preeclamptic nephropathy, the immunohistochemical study was performed in ten renal biopsy cases using antisera to human type I, III, IV, and VI collagens, fibronectin, and laminin. In preeclamptic nephropathy, the accumulation of type IV and VI collagens, fibronectin was observed in moderate amount in the mesangium and, to some extent, in the thickened capillary walls, particularly in the subendothelial layer. In segmentally sclerotic lesions seen in six cases, the amount of type IV collagen was partly decreased, whereas those of type VI collagen and fibronectin were slightly increased. Type I collagen was expressed to a mild degree in the expanded mesangium and segmentally sclerotic lesions. The results suggest that the expression of ECM in the mesangium is increased in preeclamptic nephropathy, and the deposition of ECM components may be involved in the development and the reparative process of the characteristic glomerular lesions. The formation of sclerotic lesions may be linked to the alternative accumulation of ECM components.

Clinicopathologic Analysis of Membranous Glomerulonephropathy.: Seok Hoon Jeon, Moon Hyang Park; Korean J Pathol. 1998;32(6):420-430.

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Abstract: Membranous glomerulonephropathy (MGN) is the most common primary cause of the nephrotic syndrome in adults, accounting for about 20% of the cases in most series. MGN is idiopathic in the majority of cases, however approximately 25% of adults have identifiable causes (secondary MGN). To evaluate the clinical and pathologic characteristics of MGN, we reviewed the clinical data and renal biopsies from 141 cases of MGN. The mean age of the patients at biopsy was 43 years old, but patients of all age were seen (range from 3 to 76 years of age). There were 88 males and 53 females. There were 99 idiopathic MGN cases and 42 secondary MGN cases. The associated causes of secondary MGN included hepatitis B infection (18 cases), SLE (10 cases), drugs (4 cases), post-transplantation MGN (5 cases), diabetes mellitus (4 cases), syphilis (1 case) and hepatitis B infection associated with rheumatoid arthritis. The prevalence of histologic stages by Ehrenreich and Churg was as follows. Stage I was 24 cases, stage II was 72 cases, stage III was 35 cases, and stage IV was 9 cases. All patients had proteinuria. Nephrotic syndrome was observed in 39%, edema in 73%, microscopic hematuria in 49%, gross hematuria in 28%, hypertension in 13%, and the serum creatinine level above 1.5 mg/dl was in 13%. Cases with glomerulosclerosis was observed in 45 cases with an increased percentage of glomerulosclerosis in the higher grade. Immunofluorescence (IF) examination showed predominantly granular IgG (118 cases) and C3 (84 cases) stainings along the glomerular capillary wall. In idiopathic MGN, sparse mesangial IF staining was noted up to 10% of the cases. However, mesangial IF staining in SLE was observed in 33%, hepatitis B infection in 28% and diabetes mellitus in 50%. An electron microscopic examination revealed subepithelial electron dense deposits of immune complex in all cases. The prevalence of mesangial and subendothelial electron dense deposit in idiopathic MGN was present in 19% and 6%, respectively. In SLE cases, mesangial and subendothelial deposits were observed in 78% and 56%, respectively. In hepatitis B infection, mesangial and subendothelial deposits were observed in 54% and 69%, respectively. In conclusion, immune deposits in the mesangium are scanty in idiopathic MGN, and if pronounced this should increase suspicion of underlying systemic diseases, such as SLE or other infectious diseases.

Case Report

Emphysematous Pyelonephritis in Diabetic Nephropathy A report of two cases.: Jae Ho Han, Lucia Kim, Sung Eun Kim, Soon Won Hong, Hyeon Joo Jeong; Korean J Pathol. 1999;33(5):367-370.

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Abstract PDF: Diabetic nephropathy is characterized by one or a combination of the following lesions: (1) glomerular involvement with three distinctive patterns: diffuse glomerulosclerosis, nodular glomerulosclerosis, and exudative lesions; (2) arteriolo sclerosis; (3) urinary tract bacterial infection with pyelonephritis and sometimes emphysematous pyelonephritis. Emphysematous pyelonephritis is an uncommon life-threatening and acute suppurative infection of the kidney, and usually occurs in diabetic female patients. It is characterized by the production of intraparenchymal gas. Glucose fermentation has been considered the main cause of the gas formation. We presented two illustrative nephrectomy cases of emphysematous pyelonephritis in addition to the typical pathologic features of diabetic nephropathy.

Original Articles

Type IV Collagen mRNA Expression in Human Membranous Nephropathy.: Tae Sook Kim, Jung Yeon Kim, Hye Kyoung Hong, Hyun Soon Lee; Korean J Pathol. 1999;33(11):1047-1054.

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Abstract PDF: Human membranous nephropathy (MN) is morphologically characterized by subepithelial immune complex deposits and progressive thickening of glomerular basement membranes (GBM). Studies have suggested that the enhanced secretion of classical and novel type IV collagen chains in MN contributes to spike formation and the novel type IV collagen chain is particularly related to thickening of GBM. It is unclear whether the increased accumulation of extracellular matrix (ECM) proteins in GBM is due to the increased mRNA expression for type IV collagen in glomerular visceral epithelial cells (GECs). To answer this question, we analyzed seven renal biopsies of patients with idiopathic MN using in situ hybridization. In MN, the number of GECs expressing mRNA for alpha1(IV) collagen was 2.82+/-1.80/glomerular cross section (gcs), and the number expressing mRNA for alpha4(IV) collagen was 8.42+/-2.85/gcs. The number of GECs expressing mRNA for alpha4(IV) collagen was significantly larger than that of alpha1(IV) collagen mRNA. The expression of mRNA for these ECM proteins in normal controls was negligible. These results suggest that subepithelial immune complexes stimulate the gene expression of alpha1(IV) collagen and alpha4(IV) collagen in glomerular GECs which, in turn, increase the secretion of ECM proteins and contribute to the thickening of GBM in MN.

Ultrastructural Changes in Glomerular Anionic Sites in Puromycin Aminonucleoside Nephropathy.: Hyun Chul Kim, Chan Oh Choi, Young Ho Kim, Kwan Kyu Park; Korean J Pathol. 2000;34(1):56-67.

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Abstract PDF: An ultrastructural study was done on puromycin aminonucleoside (PAN) nephropathy which was induced in a group of Sprague-Dawley rats by a single intraperitoneally injected dose. To study the ultrastructural alteration of glomerular anionic sites renal tissue was stained with polyethyleneimine (PEI) as a cationic probe. The PEI method seemed to selectively stain heparan sulfate proteoglycan in the basement membrane and has been widely used to evaluate the changes of the basement membrane in human diseases as well as in experimental work. The experimental rats developed proteinuria three days after the PAN injection. Electron microscopic studies of glomeruli showed the loss of epithelial foot processes, formation of cytoplasmic vacuoles, microvillous formation, and increased numbers of lysosomes in the cytoplasm of podocytes. The anionic sites on the basement membrane with foot process fusion were mostly indistinguishable from those seen in control rats, but focal areas of loss or disarray of anionic sites were noted. The anionic sites were not seen on the basement membrane where the overlying epithelium was detached. The results suggest that proteinuria in PAN nephrosis may be primarily due to a glomerular epithelial lesion, leading to focal disarray of anionic sites or focal defects in the epithelial covering of the basement membrane. The loss of anionic sites in the basement membrane may result partially from the foot process fusion, but mostly from the epithelial detachment.

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.

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