title: Invagination and infolding of podocytes in glomerular basement membrane in the cases of primary membranous nephropathy.
abstract: BACKGROUND
  The ultrastructural findings of membranous nephropathy (MN) are well described. Recently, podocyte infolding in the glomerular basement membrane (GBM) has been observed to be a unique ultrastructural finding formed from diffuse spherical microparticles and microtubules in the GBM. However, these alterations of glomerular epithelial cells have not been well characterized in MN.
  
  
  METHODS
  We selected 126 renal biopsies of primary MN that were diagnosed by light microscopy and immunofluorescence. In these biopsies, we investigated the ultrastructural alterations of GBM and podocytes, especially the presence of podocyte invagination, podocyte infolding, and spherical microparticles in the GBM.
  
  
  RESULTS
  In 98 cases (77.8%) we ultrastructurally detected occasional invagination of podocytes in the GBM within or around electron-dense or lucent deposits in mainly stage II-III of MN. In 40 cases (31.7%), we found spherical microparticles in addition to the podocyte invaginations in the GBM. In our cases, spherical microparticles were divided into three types; podocyte infolding, cell debris and virus-like particle types. Only one case displayed numerous spherical microparticles (microspheres) that were probably caused by infolding of podocytes. These microspheres, about 80 nm in diameter, were covered by unit membrane, and were accompanied by similar-sized microtubules and protrusions of podocytes. The spherical microparticles in the other cases were associated with cell debris (n = 23) or virus-like particles (n = 16) and were not connected with podocytes.
  
  
  CONCLUSIONS
  Podocyte invagination associated with subepithelial deposits was a common pathological finding of primary MN, especially stage II-III of MN. The spherical microparticles in GBM in the case of MN may be associated with not only podocyte infolding but also cell debris and virus-like particles. The spherical microparticles in GBM due to diffuse podocyte infolding was considered as a new pathology finding of the GBM and may appear to be a new glomerular disease entity termed podocytic infolding glomerulopathy.
authors.affiliation: Department of Analytic Human Pathology, Nippon Medical School, 1-15 Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan.
authors.forename: Yukinari
authors.initials: Y
authors.lastname: Masuda
authors.forename: Akiko
authors.initials: A
authors.lastname: Mii
authors.forename: Akira
authors.initials: A
authors.lastname: Shimizu
authors.forename: Emiko
authors.initials: E
authors.lastname: Fujita
authors.forename: Kaoru
authors.initials: K
authors.lastname: Aki
authors.forename: Kahori
authors.initials: K
authors.lastname: Ishikawa
authors.forename: Masamichi
authors.initials: M
authors.lastname: Ishizaki
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sato
authors.forename: Naoaki
authors.initials: N
authors.lastname: Hayama
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Iino
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Katayama
authors.forename: Yuh
authors.initials: Y
authors.lastname: Fukuda
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D050533:Glomerular Basement Membrane / Q000473:pathology* / Q000648:ultrastructure; D006801:Humans; D007674:Kidney Diseases / Q000473:pathology*; D008297:Male; D008854:Microscopy, Electron; D008863:Microspheres; D008875:Middle Aged; D050199:Podocytes / Q000473:pathology* / Q000648:ultrastructure