Immunohistochemical expression of podocyte markers in the variants of focal segmental glomerulosclerosis

Abstract

Background. Focal segmental glomerulosclerosis (FSGS) is the most prevalent primary glomerulopathy in Brazil and its incidence is increasing worldwide. Pathogenesis is related to podocyte injury, which may be due to several factors including viruses, drugs, immunology. In 2004, the Columbia classification of FSGS identified five histologic variants of the disease: collapsing (COL), usual (not otherwise specified, NOS), tip lesion (TIP), perihilar (PHI) and cellular variant (CEL). Several studies have demonstrated molecular changes in podocytes of FSGS patients. This study sought to classify a large series of FSGS biopsies according to the Columbia classification and analyze the occurrence of immunohistochemical differences among the five variants.Methods. Approximately 131 cases of renal biopsies with a diagnosis of primary FSGS during the period from 1996-2006 were classified according to the criteria of Columbia and were then submitted to immunohistochemical staining to the following antibodies: CD10, WT-1, Vimentin, Synaptopodin, α-actinin-4, GLEPP-1, cytokeratin (CK) 8-18, CK19 and Ki-67. Results. The FSGS classification resulted in 38.2% of NOS variant, in 36.6% COL, in 14.5% TIP, in 6.9% PHI and in 3.8% CEL. COL variant distinguished themselves among the others for having loss of expression of CD10, WT1 and α-actinin-4 (P < 0.05). Furthermore, COL gained expression of the CK8-18 and CK19 diverging from the other variants (P < 0.05). Conclusions. COL variant of FSGS presented immunohistochemical characteristics that distinguished it from others pointing to additional studies in this area. The distinct immunohistochemical properties of COL might be of help in the comprehension of this aggressive form of FSGS.

Effect of Heme Oxygenase-1 Deficiency on Glomerular Proteomics

“…The increase in keratin type I cytoskeletal protein 13 (4-fold) and type II cytoskeletal 73 (5-fold) protein in Hmox1 -/-rat glomeruli can be explained in the context of the FSGS-like lesions, since increased cytokeratin expression is known to occur in such lesions, particularly in those of the collapsing FSGS variant. Specifically, staining of kidney sections of human patients with various forms of FSGS for cytokeratins 8 and 18 using an antibody, which cross reacts with a number of cytokeratins including cytokeratin 13, revealed increased expression in podocytes of collapsing FSGS lesions [25,26] . The authors interpreted this finding as neoexpression of these cytokeratins due to podocyte de-differentiation, as cytokeratins are expressed in podocytes during embryogenesis but not in mature podocytes [27,28] .…”

Low-dose cadmium activates the JNK signaling pathway in human renal podocytes

“…3B). Specific markers of podocytes include CD2AP and synaptopodin (7). In response to extracellular stimuli, podocytes may undergo a phenotypic alteration, thus resulting in the loss of terminal differentiation markers (20,21).…”

“…Podocyte dysfunction impairs size selectivity of the glomerular filter, thus leading to proteinuria, hypoalbuminuria and edema (5). In addition, podocyte phenotype is determined by the expression of CD2-associated protein (CD2AP) and synaptopodin (7). Podocyte dedifferentiation over the course of collapsing focal segmental glomerulosclerosis results in the loss of synaptopodin and cytoskeleton markers (8,9).…”

Molecular Profiling in IgA Nephropathy and Focal and Segmental Glomerulosclerosis

“…The role of T-cell costimulating molecule B7-1 (CD80) in development of proteinuria in FSGS patients has been described (Kronbichler et al 2016). Higher expression of some molecular markers of podocytes (podoplanin and podocin) were found in FSGS (Koop et al 2003) and recently, it was shown that collapsing variant of FSGS with the worst prognosis had lower immunohistochemical expression of podocyte markers (CD10, α-actinin-4, and WT1) (Testagrossa et al 2013).…”