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http://dx.doi.org/10.3339/jkspn.2013.17.1.13

Podocytopathy and Morphologic Changes in Focal Segmental Glomerulosclerosis  

Jeong, Hyeon Joo (Department of Pathology, Yonsei University College of Medicine)
Publication Information
Childhood Kidney Diseases / v.17, no.1, 2013 , pp. 13-18 More about this Journal
Abstract
Podocytopathy is glomerular lesions characterized by podocyte injury. It is observed in various glomerular diseases, but minimal change disease and focal segmental glomerulosclerosis (FSGS) are the prototypes. In this review, morphologic features of podocyte injury and subtypes of FSGS will be reviewed briefly. Effacement of podocyte foot processes is the most common feature of podocyte injury. As podocytic injury progresses, intracytoplasmic vacuoles, subpodocytic cyst, detachment of podocytes from the glomerular basement membrane and apoptosis develop. Glomerular capillary loops in epithelium-denuded area undergo capillary collapse. Synechia and hyalinosis may accompany this lesion. To manifest segmental sclerosis, podocyte loss above a threshold level may be required. Injured podocytes can injure neighboring intact podocytes, and thereby spread injury within the same lobule. FSGS can be categorized into five subtypes by morphologic characteristics; not otherwise specified (NOS), perihilar, cellular, tip, and collapsing types. Each subtype has been reported to show different clinical courses and associated conditions, but there are controversies on its significance. With recent progress in the discovery of genetic abnormalities causing FSGS and plasma permeability factors, we expect to unravel pathophysiology of FSGS and to understand histological sequences leading to FSGS in near future.
Keywords
Focal segmental glomerulosclerosis; Morphology; Subtypes;
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1 Kambham N, Markowitz GS, Valeri AM, Lin J, D'Agati VD. Obesity-related glomerulopathy: an emerging epidemic. Kidney Int 2001;59:1498-509.   DOI   ScienceOn
2 D'Agati VD, Fogo AB, Bruijn JA, Jennette JC. Pathologic classification of focal segmental glomerulosclerosis: a working proposal. Am J Kidney Dis 2004;43:368-82.   DOI   ScienceOn
3 Thomas DB, Franceschini N, Hogan SL, Ten Holder S, Jennette CE, Falk RJ, et al. Clinical and pathologic characteristics of focal segmental glomerulosclerosis pathologic variants. Kidney Int 2006;69:920-6.   DOI   ScienceOn
4 Stokes MB, Valeri AM, Markowitz GS, D'Agati VD. Cellular focal segmental glomerulosclerosis: Clinical and pathologic features. Kidney Int 2006;70:1783-92.   DOI   ScienceOn
5 Deegens JK, Steenbergen EJ, Borm GF, Wetzels JF. Pathological variants of focal segmental glomerulosclerosis in an adult Dutch population--epidemiology and outcome. Nephrol Dial Transplant 2008;23:186-92.
6 Kim MJ, Kim D, Lim BJ, Jeong HJ. An analysis of focal segmental glomerulosclerosis according to morphologic subtypes. Korean J Pathol 2010;44:589-96.   DOI
7 D'Agati VD. The spectrum of focal segmental glomerulosclerosis: new insights. Curr Opin Nephrol Hypertens 2008;17: 271-81.   DOI   ScienceOn
8 Barisoni L, Kriz W, Mundel P, D'Agati V. The dysregulated podocyte phenotype: a novel concept in the pathogenesis of collapsing idiopathic focal segmental glomerulosclerosis and HIV-associated nephropathy. J Am Soc Nephrol 1999;10:51-61.
9 Bariety J, Nochy D, Mandet C, Jacquot C, Glotz D, Meyrier A. Podocytes undergo phenotypic changes and express macrophagic-associated markers in idiopathic collapsing glomerulopathy. Kidney Int 1998;53:918-28.   DOI   ScienceOn
10 Nagata M, Nakayama K-I, Terada Y, Hoshi S, Watanabe T. Cell cycle regulation and differentiation in the huma podocyte lineage. Am J Pathol 1998;153:1511-20.   DOI   ScienceOn
11 Dijkman H, Smeets B, van der Laak J, Steenbergen E, Wetzels J. The parietal epithelial cell is crucially involved in human idiopathic focal segmental glomerulosclerosis. Kidney Int 2005;68:1562-72.   DOI   ScienceOn
12 Howie AJ, Pankhurst T, Sarioglu S, Turhan N, Adu D. Evolution of nephrotic-associated focal segmental glomerulosclerosis and relation to the glomerular tip lesion. Kidney Int 2005;67: 987-1001.   DOI   ScienceOn
13 Canaud G, Dion D, Zuber J, Gubler M-C, Sberro R, Thervet E, et al. Recurrence of nephrotic syndrome after transplantation in a mixed population of children and adults: course of glomerular lesions and value of the Columbia classification of histological variants of focal and segmental glomerulosclerosis (FSGS). Nephrol Dial Transplant 2010;25:1321-8.   DOI   ScienceOn
14 Santin S, Bullich G, Tazon-Vega B, Garcia-Maset R, Gimenez I, Silva I, et al. Clinical utility of genetic testing in children and adults with steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol 2011;6:1139-48.   DOI   ScienceOn
15 Wei C, Hindi SE, Li J, Fornoni A, Goes N, Sageshima J, et al. Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis. Nature Med 2011;17:952-60.   DOI   ScienceOn
16 Wharram BL, Goyal M, Wiggins JE, Sanden SK, Hussain S, Filipiak WE, et al. Podocyte depletion causes glomerulosclerosis: diphtheria toxin-induced podocyte depletion in rats expressing human diphtheria toxin receptor transgene. J Am Soc Nephrol 2005;16:2941-52.   DOI   ScienceOn
17 Neal CR, Crook H, Bell E, Harper SJ, Bates DO. Threedimensional reconstruction of glomeruli by electron microscopy reveals a distinct restrictive urinary subpodocyte space. J Am Soc Nephrol 2005;16:1223-35.   DOI   ScienceOn
18 Cohen AH, Mampaso F, Zamboni L. Glomerular podocyte degeneration in human renal disease: an ultrastructural study. Lab Invest 1977;37:30-42.
19 Grishman E, Churg J. Focal glomerular sclerosis in nephrotic patients: an electron microscopic study of glomerular podocytes. Kidney Int 1975;7:111-22.   DOI   ScienceOn
20 Matsusaka T, Sandgren E, Shintani A, Kon V, Pastan I, Fogo AB, et al. Podocyte injury damages other podocytes. J Am Soc Nephrol 2011;22:1275-85.   DOI   ScienceOn
21 Howie AJ, Brewer DB. The glomerular tip lesion: a previously undescribed type of segmental glomerular abnormality. J Pathol 1984;142:205-20.   DOI
22 Beaman M, Howie AJ, Hardwicke J, Michael J, Adu D. The glomerular tip lesion: a steroid responsive nephrotic syndrome. Clin Nephrol 1987;27:217-21.
23 Schwartz MM, Lewis EJ. Focal segmental glomerular sclerosis: the cellular lesion. Kidney Int 1985;28:968-74.   DOI   ScienceOn
24 Weiss MA, Daquioag E, Margolin EG, Pollak VE. Nephrotic syndrome, progressive irreversible renal failure, and glomerular "collapse": a new clinicopathologic entity? Am J Kidney Dis 1986;7:20-8.   DOI
25 Detwiler RK, Falk RJ, Hogan SL, Jennette JC. Collapsing glomerulopathy: a clinically and pathologically distinct variant of focal segmental glomerulosclerosis. Kidney Int 1994;45:1416-24.   DOI   ScienceOn
26 Ito H, Yoshikawa N, Aozai F, Hazikano H, Sakaguchi H, Akamatsu R, et al. Twenty-seven children with focal segmental glomerulosclerosis: correlation between the segmental location of the glomerular lesions and prognosis. Clin Nephrol 1984;22: 9-14.
27 Morita M, White RH, Coad NA, Raafat F. The clinical significance of the glomerular location of segmental lesions in focal segmental glomerulosclerosis. Clin Nephrol 1990;33:211-9.
28 Meyrier AY. Collapsing glomerulopathy: expanding interest in a shrinking tuft. Am J Kidney Dis 1999;33:801-3.   DOI   ScienceOn
29 Shimamura T, Walker J. A collapsing form of glomerulopathy. Pathol Int 1995;45:520-3.   DOI   ScienceOn
30 Valeri A, Barisoni L, Appel GB, Seigle R, D'Agati V. Idiopathic collapsing focal segmental glomerulosclerosis: a clinicopathologic study. Kidney Int 1996;50:1734-46.   DOI   ScienceOn
31 Grcevska L, Polenakovik M. Collapsing glomerulopathy: clinical characteristics and follow-up. Am J Kidney Dis 1999; 33:652-7.   DOI   ScienceOn
32 Schwartz MM, Korbet SM, Rydell J, Borok R, Genchi R. Primary focal segmental glomerular sclerosis in adults: prognostic value of histologic variants. Am J Kidney Dis 1995;25:845-52.   DOI   ScienceOn