BACKGROUND AND OBJECTIVES: alpha- and beta-dystroglycan (DG), which link the actin cytoskeleton of the podocyte to the glomerular basement membrane, are maintained in FSGS but decreased in minimal change disease (MCD). Fibrosis has been linked to increased fibroblast-specific protein-1 (FSP1) and epithelial-mesenchymal transition. We studied DG, FSP1, and podocyte differentiation in FSGS variants and cases of suspected FSGS. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We studied renal biopsies with FSGS, not otherwise specified (NOS), tip lesion, or collapsing variants (COLL), versus secondary FSGS or cases without segmental sclerotic lesions where a diagnosis of MCD versus FSGS could not be established (undefined [UNDEF]) and compared the expression of DG, FSP1, and podocyte Wilms' tumor antigen (WT1). RESULTS: WT1 is markedly decreased in NOS versus normal and correlates with the extent of sclerosis. alpha- and beta-DG are maintained in most primary and secondary FSGS cases. In contrast, alpha-DG is significantly decreased in UNDEF, supporting a diagnosis of MCD. Furthermore, follow-up shows remission or decreased proteinuria in four of six of these UNDEF cases in response to therapy. Interstitial FSP1 is numerically highest in COLL but is only rarely found in tubules or podocytes in any other forms of FSGS. CONCLUSIONS: We conclude that increased FSP1 may be a marker of the aggressive course of collapsing FSGS. Furthermore, DG staining is a useful adjunct to assist in distinction of FSGS versus MCD in biopsies without defining lesions.
BACKGROUND AND OBJECTIVES: alpha- and beta-dystroglycan (DG), which link the actin cytoskeleton of the podocyte to the glomerular basement membrane, are maintained in FSGS but decreased in minimal change disease (MCD). Fibrosis has been linked to increased fibroblast-specific protein-1 (FSP1) and epithelial-mesenchymal transition. We studied DG, FSP1, and podocyte differentiation in FSGS variants and cases of suspected FSGS. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We studied renal biopsies with FSGS, not otherwise specified (NOS), tip lesion, or collapsing variants (COLL), versus secondary FSGS or cases without segmental sclerotic lesions where a diagnosis of MCD versus FSGS could not be established (undefined [UNDEF]) and compared the expression of DG, FSP1, and podocyte Wilms' tumor antigen (WT1). RESULTS:WT1 is markedly decreased in NOS versus normal and correlates with the extent of sclerosis. alpha- and beta-DG are maintained in most primary and secondary FSGS cases. In contrast, alpha-DG is significantly decreased in UNDEF, supporting a diagnosis of MCD. Furthermore, follow-up shows remission or decreased proteinuria in four of six of these UNDEF cases in response to therapy. Interstitial FSP1 is numerically highest in COLL but is only rarely found in tubules or podocytes in any other forms of FSGS. CONCLUSIONS: We conclude that increased FSP1 may be a marker of the aggressive course of collapsing FSGS. Furthermore, DG staining is a useful adjunct to assist in distinction of FSGS versus MCD in biopsies without defining lesions.
Authors: D B Thomas; N Franceschini; S L Hogan; S Ten Holder; C E Jennette; R J Falk; J C Jennette Journal: Kidney Int Date: 2006-03 Impact factor: 10.612
Authors: H Yamada; A J Denzer; H Hori; T Tanaka; L V Anderson; S Fujita; H Fukuta-Ohi; T Shimizu; M A Ruegg; K Matsumura Journal: J Biol Chem Date: 1996-09-20 Impact factor: 5.157
Authors: Mariana Murea; Jun-Ki Park; Shuchita Sharma; Hideki Kato; Antje Gruenwald; Thiruvur Niranjan; Han Si; David B Thomas; James M Pullman; Michal L Melamed; Katalin Susztak Journal: Kidney Int Date: 2010-06-09 Impact factor: 10.612
Authors: Huma Fatima; Marcus J Moeller; Bart Smeets; Hai-Chun Yang; Vivette D D'Agati; Charles E Alpers; Agnes B Fogo Journal: Clin J Am Soc Nephrol Date: 2012-08-23 Impact factor: 8.237
Authors: Bart Smeets; Fabien Stucker; Jack Wetzels; Isabelle Brocheriou; Pierre Ronco; Hermann-Josef Gröne; Vivette D'Agati; Agnes B Fogo; Toin H van Kuppevelt; Hans-Peter Fischer; Peter Boor; Jürgen Floege; Tammo Ostendorf; Marcus J Moeller Journal: Am J Pathol Date: 2014-10-07 Impact factor: 4.307