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

Clin Exp Nephrol. 2015 Jun;19(3):427-35. doi: 10.1007/s10157-014-1008-8. Epub 2014 Jul 24.

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.

Conclusion: 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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Capillaries / chemistry
  • Capillaries / injuries
  • Capillaries / ultrastructure
  • Collagen Type IV / analysis*
  • Female
  • Glomerular Basement Membrane / chemistry*
  • Glomerular Basement Membrane / injuries
  • Glomerular Basement Membrane / pathology
  • Glomerular Basement Membrane / ultrastructure*
  • Glomerulonephritis, IGA / metabolism
  • Glomerulonephritis, IGA / pathology*
  • Humans
  • Kidney Glomerulus / blood supply
  • Kidney Glomerulus / chemistry
  • Kidney Glomerulus / diagnostic imaging
  • Male
  • Microscopy, Electron, Scanning / methods
  • Microscopy, Electron, Transmission
  • Middle Aged
  • Ultrasonography
  • Young Adult

Substances

  • COL4A2 protein, human
  • COL4A5 protein, human
  • Collagen Type IV