Journal of Pathology and Translational Medicine

Review

Pathogenesis of Focal Segmental Glomerulosclerosis: Beom Jin Lim, Jae Won Yang, Woo Sung Do, Agnes B. Fogo; J Pathol Transl Med. 2016;50(6):405-410. Published online October 16, 2016; DOI: https://doi.org/10.4132/jptm.2016.09.21

13,220 View
874 Download
48 Web of Science
44 Crossref

Focal segmental glomerulosclerosis (FSGS) is characterized by focal and segmental obliteration of glomerular capillary tufts with increased matrix. FSGS is classified as collapsing, tip, cellular, perihilar and not otherwise specified variants according to the location and character of the sclerotic lesion. Primary or idiopathic FSGS is considered to be related to podocyte injury, and the pathogenesis of podocyte injury has been actively investigated. Several circulating factors affecting podocyte permeability barrier have been proposed, but not proven to cause FSGS. FSGS may also be caused by genetic alterations. These genes are mainly those regulating slit diaphragm structure, actin cytoskeleton of podocytes, and foot process structure. The mode of inheritance and age of onset are different according to the gene involved. Recently, the role of parietal epithelial cells (PECs) has been highlighted. Podocytes and PECs have common mesenchymal progenitors, therefore, PECs could be a source of podocyte repopulation after podocyte injury. Activated PECs migrate along adhesion to the glomerular tuft and may also contribute to the progression of sclerosis. Markers of activated PECs, including CD44, could be used to distinguish FSGS from minimal change disease. The pathogenesis of FSGS is very complex; however, understanding basic mechanisms of podocyte injury is important not only for basic research, but also for daily diagnostic pathology practice.

Citations

Citations to this article as recorded by

Focal segmental glomerulosclerosis associated with undescribed mutation in the LMX1B gene
María Adoración Martín Gómez, Mercedes Caba Molina, Miriam León Fradejas, Juana Alonso Titos, Rafael del Pozo Alvarez
European Journal of Medical Genetics.2024; 72: 104980. CrossRef
MicroRNA-155-5p Aggravates Adriamycin-Induced Focal Segmental Glomerulosclerosis through Targeting Nrf2
Guoyong Liu, Liyu He, Xiaomeng Yang, Lingling Tang, Wei Shi, Jian She, Jiali Wei
Nephron.2023; 147(2): 108. CrossRef
The role of HLA antigens in recurrent primary focal segmental glomerulosclerosis
Ibrahim Batal, Pascale Khairallah, Astrid Weins, Nicole K. Andeen, Michael B. Stokes
Frontiers in Immunology.2023;[Epub] CrossRef
IgM and C3 Deposition in Primary Focal Segmental Glomerulosclerosis (FSGS): A Clinical and Histopathological Spectrum
Faizan Amer, Madiha Syed , Aurangzeb Afzal, Mudassar Hussain , Usman Hassan, Shaarif Bashir, Maryam Hameed, Sheeba Ishtiaq
Cureus.2023;[Epub] CrossRef
Identification of key biomarkers of the glomerulus in focal segmental glomerulosclerosis and their relationship with immune cell infiltration based on WGCNA and the LASSO algorithm
Yun Xia Zhang, Juan Lv, Jun Yuan Bai, XiaoWei Pu, En Lai Dai
Renal Failure.2023;[Epub] CrossRef
Rituximab in the treatment of primary FSGS: time for its use in routine clinical practice?
Adam D Morris, Lauren Floyd, Alexander Woywodt, Ajay Dhaygude
Clinical Kidney Journal.2023; 16(8): 1199. CrossRef
High Rate of Mutations of Adhesion Molecules and Extracellular Matrix Glycoproteins in Patients with Adult-Onset Focal and Segmental Glomerulosclerosis
Sara Marcos González, Emilio Rodrigo Calabia, Ignacio Varela, Michal Červienka, Javier Freire Salinas, José Javier Gómez Román
Biomedicines.2023; 11(6): 1764. CrossRef
Glomerular parietal epithelial expression of CD44 in minimal change nephrotic syndrome and primary focal segmental glomerulosclerosis: A clinico-pathological study
ENithin Paul, Suchitha Satish, KiranKrishnamurthy Kelur, ManjunathSanjeev Shetty
Indian Journal of Pathology and Microbiology.2023; 66(3): 526. CrossRef
Calcineurin inhibitors or cyclophosphamide in the treatment of membranous nephropathy superimposed with FSGS lesions: a retrospective study from China
Hong-Guang He, Yi-Yun Huang, Qin-Qing Liang, Qiu-Rong Ye, An-Dong Li, Kun Ye, Qiu-Xia Wu, Yan-Wu You
Renal Failure.2023;[Epub] CrossRef
CD44-negative parietal–epithelial cell staining in minimal change disease: association with clinical features, response to corticosteroids and kidney outcome
Neus Roca, Elias Jatem, Anabel Abo, Maria Santacana, Alejandro Cruz, Álvaro Madrid, Gloria Fraga, Marisa Martin, Jorge Gonzalez, Cristina Martinez, Anna Balius, Alfons Segarra
Clinical Kidney Journal.2022; 15(3): 545. CrossRef
Monogenic focal segmental glomerulosclerosis: A conceptual framework for identification and management of a heterogeneous disease
Meenakshi Sambharia, Prerna Rastogi, Christie P. Thomas
American Journal of Medical Genetics Part C: Seminars in Medical Genetics.2022; 190(3): 377. CrossRef
Small Nucleolar RNAs in Pseudoexfoliation Glaucoma
Karolina Gasińska, Marcin Czop, Ewa Kosior-Jarecka, Dominika Wróbel-Dudzińska, Janusz Kocki, Tomasz Żarnowski
Cells.2022; 11(17): 2738. CrossRef
Collapsing focal segmental glomerulosclerosis in a patient with oral cavity cancer
Sae Byeol Choi, Kyoung Min Kim, Moon Hyang Park, Kyung Pyo Kang
Medicine.2021; 100(18): e25857. CrossRef
MRTF: Basic Biology and Role in Kidney Disease
Maria Zena Miranda, Zsuzsanna Lichner, Katalin Szászi, András Kapus
International Journal of Molecular Sciences.2021; 22(11): 6040. CrossRef
The Unique Difference Between Serum Level of Soluble Urokinase Plasminogen Activator Receptor (suPAR) in Steroid-Resistant Nephrotic Syndrome Children Treated with an Alkylating Agent and Calcineurin Inhibitors
Ahmedz Widiasta, Kurnia Wahyudi, Husna Nugrahapraja, Yunia Sribudiani, Dedi Rachmadi
Journal of Comprehensive Pediatrics.2021;[Epub] CrossRef
Recessive, gain-of-function toxicity in an APOL1 BAC transgenic mouse model mirrors human APOL1 kidney disease
Gizelle M. McCarthy, Angelo Blasio, Olivia G. Donovan, Lena B. Schaller, Althea Bock-Hughes, Jose M. Magraner, Jung Hee Suh, Calum F. Tattersfield, Isaac E. Stillman, Shrijal S. Shah, Zsuzsanna K. Zsengeller, Balajikarthick Subramanian, David J. Friedman,
Disease Models & Mechanisms.2021;[Epub] CrossRef
CLEC14A protects against podocyte injury in mice with adriamycin nephropathy
Zeyu Su, Yujia Li, Hang Lv, Xiaoyang Cui, Min Liu, Ziying Wang, Yan Zhang, Junhui Zhen, Wei Tang, Xiaojie Wang, Fan Yi
The FASEB Journal.2021;[Epub] CrossRef
Interplay between extracellular matrix components and cellular and molecular mechanisms in kidney fibrosis
Sandra Rayego-Mateos, Sofia Campillo, Raúl R. Rodrigues-Diez, Antonio Tejera-Muñoz, Laura Marquez-Exposito, Roel Goldschmeding, Diego Rodríguez-Puyol, Laura Calleros, Marta Ruiz-Ortega
Clinical Science.2021; 135(16): 1999. CrossRef
The recruitment mechanisms and potential therapeutic targets of podocytes from parietal epithelial cells
Lihua Ni, Cheng Yuan, Xiaoyan Wu
Journal of Translational Medicine.2021;[Epub] CrossRef
miR-150 inhibitor ameliorates adriamycin-induced focal segmental glomerulosclerosis
Huimeng Qi, Jingqi Fu, Junjun Luan, Congcong Jiao, Xiangfei Cui, Xiangyan Cao, Yixiao Zhang, Yanqiu Wang, Jeffrey B. Kopp, Jingbo Pi, Hua Zhou
Biochemical and Biophysical Research Communications.2020; 522(3): 618. CrossRef
From protein uptake to Dent disease: An overview of the CLCN5 gene
Lisa Gianesello, Dorella Del Prete, Monica Ceol, Giovanna Priante, Lorenzo Arcangelo Calò, Franca Anglani
Gene.2020; 747: 144662. CrossRef
Non-ischemic cardiomyopathy with focal segmental glomerulosclerosis
Parminder Kaur, Balraj Singh, Prem Patel, Rahul Vasudev, Upamanyu Rampal, Fayez Shamoon
Journal of Community Hospital Internal Medicine Perspectives.2020; 10(2): 154. CrossRef
Glomerular Endothelial Cells as Instigators of Glomerular Sclerotic Diseases
Marloes Sol, Jan A. A. M. Kamps, Jacob van den Born, Marius C. van den Heuvel, Johan van der Vlag, Guido Krenning, Jan-Luuk Hillebrands
Frontiers in Pharmacology.2020;[Epub] CrossRef
A novel heterozygous variant of the COL4A4 gene in a Chinese family with hematuria and proteinuria leads to focal segmental glomerulosclerosis and chronic kidney disease
Liang‐Liang Fan, Lv Liu, Fang‐Mei Luo, Ran Du, Chen‐Yu Wang, Yi Dong, Ji‐Shi Liu
Molecular Genetics & Genomic Medicine.2020;[Epub] CrossRef
Cellular and molecular mechanisms of kidney fibrosis
Sonja Djudjaj, Peter Boor
Molecular Aspects of Medicine.2019; 65: 16. CrossRef
Albumin induces CD44 expression in glomerular parietal epithelial cells by activating extracellular signal‐regulated kinase 1/2 pathway
Xueying Zhao, Xiaoming Chen, Ashmeer Chima, Yuanyuan Zhang, Jasmine George, Alyssa Cobbs, Nerimiah Emmett
Journal of Cellular Physiology.2019; 234(5): 7224. CrossRef
Analysis of the genomic architecture of a complex trait locus in hypertensive rat models links Tmem63c to kidney damage
Angela Schulz, Nicola Victoria Müller, Nina Anne van de Lest, Andreas Eisenreich, Martina Schmidbauer, Andrei Barysenka, Bettina Purfürst, Anje Sporbert, Theodor Lorenzen, Alexander M Meyer, Laura Herlan, Anika Witten, Frank Rühle, Weibin Zhou, Emile de H
eLife.2019;[Epub] CrossRef
Podocyte-Specific Sialylation-Deficient Mice Serve as a Model for Human FSGS
Kristina M. Niculovic, Linda Blume, Henri Wedekind, Elina Kats, Iris Albers, Stephanie Groos, Markus Abeln, Jessica Schmitz, Esther Beuke, Jan H. Bräsen, Anette Melk, Mario Schiffer, Birgit Weinhold, Anja K. Münster-Kühnel
Journal of the American Society of Nephrology.2019; 30(6): 1021. CrossRef
Inhibition of the ERK1/2-mTORC1 axis ameliorates proteinuria and the fibrogenic action of transforming growth factor-β in Adriamycin-induced glomerulosclerosis
Ranjan Das, Soo-Jin Kim, Nhung Thi Nguyen, Hyeong Ju Kwon, Seung-Kuy Cha, Kyu-Sang Park
Kidney International.2019; 96(4): 927. CrossRef
Mechanisms of Scarring in Focal Segmental Glomerulosclerosis
Jianyong Zhong, Jacob B. Whitman, Hai-Chun Yang, Agnes B. Fogo
Journal of Histochemistry & Cytochemistry.2019; 67(9): 623. CrossRef
A bigenic mouse model of FSGS reveals perturbed pathways in podocytes, mesangial cells and endothelial cells
Andrew S. Potter, Keri Drake, Eric W. Brunskill, S. Steven Potter, Peter Hohenstein
PLOS ONE.2019; 14(8): e0216261. CrossRef
Chronic kidney disease: a review of proteomic and metabolomic approaches to membranous glomerulonephritis, focal segmental glomerulosclerosis, and IgA nephropathy biomarkers
Amir Taherkhani, Reyhaneh Farrokhi Yekta, Maede Mohseni, Massoud Saidijam, Afsaneh Arefi Oskouie
Proteome Science.2019;[Epub] CrossRef
Sphingolipid signaling in renal fibrosis
Andrea Huwiler, Josef Pfeilschifter
Matrix Biology.2018; 68-69: 230. CrossRef
A novel assay provides sensitive measurement of physiologically relevant changes in albumin permeability in isolated human and rodent glomeruli
Sara Desideri, Karen L. Onions, Yan Qiu, Raina D. Ramnath, Matthew J. Butler, Christopher R. Neal, Matthew L.R. King, Andrew E. Salmon, Moin A. Saleem, Gavin I. Welsh, C. Charles Michel, Simon C. Satchell, Andrew H.J. Salmon, Rebecca R. Foster
Kidney International.2018; 93(5): 1086. CrossRef
Recent advances of animal model of focal segmental glomerulosclerosis
Jae Won Yang, Anne Katrin Dettmar, Andreas Kronbichler, Heon Yung Gee, Moin Saleem, Seong Heon Kim, Jae Il Shin
Clinical and Experimental Nephrology.2018; 22(4): 752. CrossRef
Urinary podocyte-associated molecules and albuminuria in hypertension
Javier Perez-Hernandez, Maria D. Olivares, Elena Solaz, Fernando Martinez, Sergio Martínez-Hervas, Gernot Pichler, Felipe J. Chaves, Josep Redon, Raquel Cortes
Journal of Hypertension.2018; 36(8): 1712. CrossRef
Segmental Sclerosis and Extracapillary Hypercellularity Predict Diabetic ESRD
Amy K. Mottl, Adil Gasim, Fernanda Payan Schober, Yichun Hu, Askia K. Dunnon, Susan L. Hogan, J. Charles Jennette
Journal of the American Society of Nephrology.2018; 29(2): 694. CrossRef
Chlormethine Hydrochloride is Not Inferior to Tacrolimus in Treating Steroid-Resistant Nephrotic Syndrome
Yuan Yang, Li Zhao, Li Xiao, Yumei Liang, Chang Wang, Xiao Fu, Xuejing Zhu, Shuguang Yuan, Jianling Zhu, Xiaoping Zhu, Yinghong Liu, Jun Li, Jian Luo, Fuyou Liu, Lin Sun
Kidney and Blood Pressure Research.2018; 43(1): 68. CrossRef
Can podocytes be regenerated in adults?
Stuart J. Shankland, Benjamin S. Freedman, Jeffrey W. Pippin
Current Opinion in Nephrology and Hypertension.2017; 26(3): 154. CrossRef
Plasma exchange in kidney transplantation: Still a valuable option for nephrotic syndrome recurrence
Licia Peruzzi, Roberto Albiani, Karol Giancaspero
Transfusion and Apheresis Science.2017; 56(4): 525. CrossRef
Is CD44 in glomerular parietal epithelial cells a pathological marker of renal function deterioration in primary focal segmental glomerulosclerosis?
Brunna Pinto Froes, Stanley de Almeida Araújo, Eduardo Alves Bambirra, Eduardo Araújo Oliveira, Ana Cristina Simões e Silva, Sérgio Veloso Brant Pinheiro
Pediatric Nephrology.2017; 32(11): 2165. CrossRef
Injury-induced actin cytoskeleton reorganization in podocytes revealed by super-resolution microscopy
Hani Y. Suleiman, Robyn Roth, Sanjay Jain, John E. Heuser, Andrey S. Shaw, Jeffrey H. Miner
JCI Insight.2017;[Epub] CrossRef
Resveratrol Attenuates Adriamycin-Induced Focal Segmental Glomerulosclerosis through C3aR/C5aR- Sphingosine Kinase 1 Pathway
Guoyong Liu, Qiang Wang, Yan Shi, Xiaofei Peng, Hong Liu, Youming Peng, Liyu He
Pharmacology.2017; 100(5-6): 253. CrossRef
The Multifaceted Role of the Lysosomal Protease Cathepsins in Kidney Disease
Pasquale Cocchiaro, Valeria De Pasquale, Rossella Della Morte, Simona Tafuri, Luigi Avallone, Anne Pizard, Anna Moles, Luigi Michele Pavone
Frontiers in Cell and Developmental Biology.2017;[Epub] CrossRef

Original Articles

C1q Nephropathy: A Distinct Pathologic Entity.: Jung Ha Shin, Tae Eun Kim, Kyo Young Lee, Sang In Shim, Yeong Jin Choi; Korean J Pathol. 2009;43(4):335-341.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.4.335

2,875 View
41 Download

Abstract PDF: BACKGROUND
C1q nephropathy (C1qN) is a controversial diagnostic entity defined by Jennette and Hipp in 1985. The prevalence is very low and a few large scale studies have been reported. Application of the criteria for clinical diagnostics of C1qN may cause confusion with other glomerulonephropathies, such as minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS). In order to clarify the confusion with glomerulonephropathies, we did this study to identify the clinicopathological characteristics and the exact disease entity of C1qN.
METHODS
A total of 5,258 kidney biopsies at Kangnam St Mary's Hospital were reviewed. Twenty three cases (0.44%) met the criteria of C1qN. Twenty eight cases showing dominant C1q deposits without electron dense depostis (EDD) grouped as C1q+EDD-, and previously diagnosed typical cases of MCD and FSGS were selected for this study. Four groups were compared to each other with regard to the clinical and pathological aspects of the disease. RESULTS: C1qN patients had an average age of 30.4 years. Eighteen were males and 5 were females. Eighty seven percent had proteinuria and 18% had hematuria. By electron microscopy analysis, 100% had mesangial EDD and 47.8% showed foot process effacement. C1qN had some significant differences compared with C1q+EDD-, MCD and FSGS. CONCLUSIONS: C1qN is clinically and morphologically different from MCD and FSGS. However, additional long term studies are needed to fully define C1qN from other glomerulonephritis with C1q deposits.

Glomerular Hypertrophy in Focal Segmental Glomerulosclerosis.: So Dug Lim, Tae Sook Kim, Hyun Soon Lee; Korean J Pathol. 1995;29(4):423-430.

1,840 View
19 Download

Abstract PDF: It is not clear whether glomerular hypertrophy is related to the pathogenesis of focal segmental glomerulosclerosis (FSGS). We analyzed renal biopsies from 20 adults with FSGS by morphometry, and the data were compared with those from age- and sex-matched patients with minimal lesion. Mean glomerular volume in the FSGS group was significantly larger than that in the minimal lesion group[(3.4 + 1.1 vs 2.5 0.5)x10(6) micrometer3, P<0.01]. The percentage of glomeruli with global and segmental sclerosis in FSGS group was significantly correlated with the mean glomerular volume (r=+0.66, P<0.001). Relative interstitial volume of renal cortex in the FSGS group was correlated with the serum creatinine concentration(r=+0.5, P<0.05). These results suggest that glomerular hypertrophy observed in our patients with FSGS was related to nephron loss caused by glomerulosclerosis. The interstitial fibrosis may lead to obliteration of postglomerular interstitial capillary network with secondary elevation of glomerular capillary pressure resulting in progressive loss of renal function.

Morphometric Analysis of Preeciamptic Nephropathy with Focal Segmental Glomerulosclerosis.: Tae Sook Kim, Hyun Soon Lee; Korean J Pathol. 1995;29(5):624-633.

1,692 View
10 Download

Abstract: To evaluate the structural characteristics that might be related to the clinical features noted in preeclamptic patients with focal segmental glomerulosclerosis(FSGS), we analyzed post-partum renal biopsies of 8 preeclamptic patients with FSGS (group 1) by morphometry and glomerular studied the structural-functional relationships. These findings were also compared with those from three postpartum cases with minimal change lesion(group 2) and normal age-matched women(group 3). Mean glomerular volume (MGV) in group 1 and group 2 was (2.64 +/- 0.49) x 10(6) micrometer3 and (2.56+/-0.25)x 10(6) micrometer3, respectively. MGV in both groups was significantly increased compared with that of the control group [(1.11+/-0.22)x10(6) micrometer3](p<0.0005). The volume density of the mesangium/glomerulus [Vv(mes/glom)] in the group 1 patients was significantly increased (p<0.0001) when compared with that of the group 2 and the control group patients. The increment of Vv(mes/glom) was related to both the mesangial cell proliferation and expansion of mesangial matrix. The volume density of the capillary lumen/glomerulus [Vv(cap/glom)] in group I was significantly decreased(p<0.0001) when compared with that of group 2 and the control group. Vv(cap/glom) was directly related to Ccr in group l(r=0.70, p=0.05). These results suggest that reduced capillary luminal area caused by mesangial interposition is related to the decreased glomerular filtration rate in preeclamptic FSGS.

Comparison of Glomerular Size between Focal Segmental Glomerulosclerosis and Minimal Lesion in Children.: Jung Yeon Kim, Hyun Soon Lee; Korean J Pathol. 1996;30(10):903-911.

1,726 View
22 Download

Abstract PDF: The pathogenetic mechanism of focal segmental glomerulosclerosis (FSGS) is not known. Some authors suggest glomerular hypertrophy may precede the development of FSGS in patients with minimal lesion. It was recently reported that the size of nonsclerotic glomeruli in adults with FSGS is significantly larger than that of cases with minimal lesion. It is not clear whether glomerular hypertrophy observed in adults with FSGS is also seen in children with FSGS. Thus, we have analyzed 37 renal biopsies from children with FSGS by morphometry and the data were compared with 37 renal biopsies from age- and sex-matched patients with minimal lesion. The number of glomeruli submitted for morphometric analysis was 22.6+/-14.2 in cases with FSGS and 30.9+/-11.4 in cases with minimal lesion. Mean glomerular volume (MGV) in FSGS group was significantly larger than that of minimal lesion [(13.1+/-3.9) x10(5) microm3 vs. (10.1+/-1.9) x10(5) microm3, p<0.001]. The relative interstitial volume of renal cortex in patients with FSGS was significantly larger than that of minimal lesion [(0.106+/-0.051) microm3/microm3 vs. (0.029+/-0.012) microm3/microm3, p<0.0001]. In FSGS, the percentage of glomeruli with FSGS was significantly correlated with relative interstitial volume of renal cortex (r=0.79, p<0.0001). As is the case for adult FSGS, MGV of children with FSGS is significantly larger than that of minimal lesion. Thus, the presence of glomerular hypertrophy observed in biopsies with minimal lesion nephropathy seems to be an indication that the coexistent FSGS lesions are undetected due to sampling problems.

The Effects of Cyclosporine A on Minimal Change Nephrosis and Focal Segmental Glomerulosclerosis Induced by Administration of Puromycin Aminonucleoside in Rats.: Sun Hee Sung; Korean J Pathol. 1996;30(11):981-997.

1,699 View
19 Download

Abstract PDF: Cyclosporine A(CsA) is known as a potent immunosupressive agent, and recently its supressive effects of proteinuria in minimal change nephrotic syndrome, and other glomerular diseases have been demonstrated. But the mechanism of supression of proteinuria is not clear. This study aimed to investigate the mechanism of supression of proteinuria in puromycin aminonucleoside (PAN) induced minimal change nephrosis(MCN), by a single dose of PAN, and focal segmental glomerulosclerosis(FSG) by long term repeated administration of PAN with unilateral nephrectomy in Sprague-Dawley rats, using transmission electron microscopy. We also analysed the effects of CsA on the histopathologic changes such as glomerular sclerosis, and subtypes of infiltrated mononuclear cells in glomeruli and renal interstitium. The results are as follows: Marked proteinuria was developed in MCN and FSG groups. It was significantly reduced by administration of CsA. BUN and creatinine were significantly increased in FSG with the administration of CsA, compared with FSG without CsA. On ultrastructural examination, MCN group showed effacement of foot processes, and microvillous transformation. Occasional focal detatchment of podocytes from the GBM, vacuolar degeneration, and electron dense droplets in the podocytes were also seen. The latter findings were remarkably reduced by CsA. The Above ultrastructural findings, seen in the MCN group, were more severe in the FSG groups. On comparison of ultrastructural fingings of FSG with or without CsA groups, severe vacuolar degeneration, abundant electron dense granules, and focal detatchment of foot processes were more frequently seen in FSG groups and they were significantly reduced by CsA. But irregularity and thickening of GBM were deepend in FSG with CsA group. There were no significant differences of glomerular sclerosis, adhesion to the Bowman's capsules in both the MCN and the FSG groups by administration of CsA. Foamy degeneration of endothelial and mesangial cells, epithelial proliferation, hyalinosis and mononuclear infiltration were significantly reduced by CsA in FSG groups. Microcalcification was commonly seen in CsA administrated groups. The main sutype of infiltrated mononuclear cells in glomeruli and interstitium were monocytes in FSG groups. The proportion of T cells were higher in interstitium by disease progression and it was significantly decreased by CsA. On conclusion the most important ultrastructural changes, regarded as the main mechanism of supression of proteinuria is that the CsA stabilize the podocytes, by preventing vacuolar degeneration and focal detatchment. But CsA does not influence the progression of glomerular sclerosis in PAN induced nephrosis.

Experimental Study of the Progressive Glomerulosclerosis Induced by Long-term Administration of Puromycin Aminonucleoside in Rats.: Mi Kyung Kim, Hyun Soon Lee; Korean J Pathol. 1993;27(1):1-10.

1,501 View
14 Download

Abstract PDF: Pathogenetic mechanisms of progressive glomerulosclerosis are not clear. We studied the long-term(10 weeks) effects of puromycin aminonucleoside(PAN) in Sprague-Dawley rats with or without uninephrectomy(UN). Compared to rats with PAN injections only, rats with uninephrectomy and PAN injections showed significantly higher serum levels of urea nitrogen(153 +/- 155 mg/dl vs. 16 +/- 4 mg/dl, p<0.01), ceatinine(2.96 +/- 1.21 mg/dl vs. 0.92 +/- 0.36 mg/dl, p<0.01), cholesterol(466 +/- 125 mg/dl vs. 94 +/- 27 mg/dl, p<0.01), and triglyceride(337 +/- 237 mg/dl vs. 111 +/- 36 mg/dl, p<0.05) as well as increased amounts of proteinuria(428 +/- 90 mg/day vs. 136 +/- 130 mg/day, p<0.01). Lesions of focal segmental glomerulosclerosis(FSGS) were more frequently observed in rats with UN and PAN injections than rats with PAN infections only(39.5 +/- 17.2% vs. 4.3 +/- 4.7%, p<0.01). Ultrastructural examination of the glomeruli from rats with UN and PAN injections revealed severe epithelial cell changes including foot process effacement, vaculoar change or pseudocyst formation and focal detachment of epithelial cells from the underlying basement membrane. The results suggest that chronic nephrosis induced by PAN showed functional and morphologic features similar to those of human FSGS. Cytotoxic effect of PAN on the glomerular epithelial cells may be an initiating factor for the development of FSGS. which may be aggravated by some hemodynamic changes induced by uninephrectomy.

First
Prev
Page of 1
Next
Last

Search