title: Glomerular basement membrane injuries in IgA nephropathy evaluated by double immunostaining for α5(IV) and α2(IV) chains of type IV collagen and low-vacuum scanning electron microscopy.
abstract: BACKGROUND
  The glomerulus contains well-developed capillaries, which are at risk of injury due to high hydrostatic pressure, hyperfiltration, hypertension and inflammation. However, the pathological alterations of the injured glomerular basement membrane (GBM), the main component of the glomerular filtration barrier, are still uncertain in cases of glomerulonephritis.
  
  
  METHODS
  We examined the alterations of the GBM in 50 renal biopsy cases with IgA nephropathy (31.8 ± 17.6 years old) using double immunostaining for the α2(IV) and α5(IV) chains of type IV collagen, and examining the ultrastructural alterations by transmission electron microscopy (TEM) and low-vacuum scanning electron microscopy (LV-SEM).
  
  
  RESULTS
  The GBM of IgA nephropathy cases showed various morphological and qualitative alterations. In the TEM findings, thinning, gaps, rupture, thickening with a lamellar and reticular structure and double contours were detected in the GBM. Double immunostaining for α5(IV) and α2(IV) showed thickening of the GBM with reduced α5(IV) and increased α2(IV), or mosaic images of α5(IV) and α2(IV), and holes, fractures, spiny projections and rupture of α5(IV) in the GBM. In addition, LV-SEM showed an etched image and multiple holes in a widening and wavy GBM. These findings might be associated with the development of a brittle GBM in IgA nephropathy.
  
  
  CONCLUSIONS
  Glomerular basement membrane alterations were frequently noted in IgA nephropathy, and were easily evaluated by double immunostaining for α2(IV) and α5(IV) of type IV collagen and LV-SEM. The application of these analyses to human renal biopsy specimens may enhance our understanding of the alterations of the GBM that occur in human glomerular diseases.
authors: Department of Analytic Human Pathology, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan. y.masuda@nms.ac.jp.
authors: Yukinari
authors: Y
authors: Masuda
authors: Tokyo Kidney Research Institute, Tokyo, Japan.
authors: Nobuaki
authors: N
authors: Yamanaka
authors: Department of Analytic Human Pathology, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan.
authors: Arimi
authors: A
authors: Ishikawa
authors: Department of Analytic Human Pathology, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan.
authors: Mitue
authors: M
authors: Kataoka
authors: Department of Analytic Human Pathology, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan.
authors: Takashi
authors: T
authors: Arai
authors: Department of Analytic Human Pathology, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan.
authors: Kyoko
authors: K
authors: Wakamatsu
authors: Department of Analytic Human Pathology, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan.
authors: Naomi
authors: N
authors: Kuwahara
authors: Department of Analytic Human Pathology, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan.
authors: Kiyotaka
authors: K
authors: Nagahama
authors: Hitachi High-Technologies Corporation, Tokyo, Japan.
authors: Kaori
authors: K
authors: Ichikawa
authors: Department of Analytic Human Pathology, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan.
authors: Akira
authors: A
authors: Shimizu
mesh_terms: D000293:Adolescent; D000328:Adult; D002196:Capillaries / Q000737:chemistry / Q000293:injuries / Q000648:ultrastructure; D024141:Collagen Type IV / Q000032:analysis*; D005260:Female; D050533:Glomerular Basement Membrane / Q000737:chemistry* / Q000293:injuries / Q000473:pathology / Q000648:ultrastructure*; D005922:Glomerulonephritis, IGA / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007678:Kidney Glomerulus / Q000098:blood supply / Q000737:chemistry / Q000000981:diagnostic imaging; D008297:Male; D008855:Microscopy, Electron, Scanning / Q000379:methods; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D014463:Ultrasonography; D055815:Young Adult
chemical_list: C502625:COL4A2 protein, human; C478159:COL4A5 protein, human; D024141:Collagen Type IV
keywords: Glomerular basement membrane; IgA nephropathy; Low-vacuum scanning electron microscopy; α2(IV) chain of type IV collagen; α5(IV) chain of type IV collagen