Ultrastructural Study of Electron Dense Deposits in Renal Tubular Basement Membrane: Prevalence and Relationship to Epithelial Atrophy

Abstract

This study reports the prevalence of immune deposits associated with the proximal and distal tubules in a series of routine renal biopsies received in our department during a single calendar year. From 87 cases, 65 (74%) were found to have glomerular immune deposits by immunofluorescence. Tubular immune deposits were found in 12 cases (18%), 3 of which had no glomerular deposits. By transmission electron microscopy (EM), 58 cases (66%) were found to have deposits of granular or vesicular material associated with the tubular basement membranes (TBM). Finely granular electron dense deposits appeared to correspond to the immune deposits seen by immunofluorescence microscopy (IF) and may be a sensitive marker of immune deposition.

Monoclonal immunoglobulin G deposits on tubular basement membrane in renal allograft: is this significant for chronic allograft injury?

“…In disease conditions there may be alterations of the protein in any of the tubular compartments and these alterations enhance complement activation, endocytic activity and upregulation of genes, leading to the production of mediators that induce inflammation, tubular degeneration and fibrosis [23]. The deposition of immune material in TBM is part of a spectrum of ultrastructural changes that may cause functional changes in the tubular epithelium [24]. Such changes are expected to be associated with progressive tubular atrophy.…”

Tubular basement membrane immune complex deposition is associated with activity and progression of lupus nephritis: a large multicenter Chinese study

“…also found that EM might be a more sensitive method for the detection of immune deposits, because electron-dense granular material was found in the TBMs of 27 cases, including lupus nephritis and other Ig deposition diseases, in which only 12 cases were positive by IF. 13 The IF results are easily influenced by several factors, including specimen handling, immunostaining with antibodies and evaluation of fluorescence. Good preservation of antigens in the fresh unfixed tissue is essential for IF staining, and instant freezing of tissue or storage in an antigen-protective solution such as Zeus’s solution should be performed, especially for specimens transported from a remote location.…”

“…The non-immune electron densities were excluded carefully in our observation; these densities were generally electron pale, possibly contained spherical structures, were located external to the TBM, and could be larger in size than the immune deposits. 13 Electron-dense deposits could exhibit a granular, patchy or strip pattern along the TBM (Supplementary Figure 1). The pattern varies between patients, and the intensity of the TBM deposits can also differ from one another.…”

“…The pattern varies between patients, and the intensity of the TBM deposits can also differ from one another. Thus, the semi-quantitative scores of the different intensities were applied as follows: Grade 0, no TBM deposits; Grade 1, presence of sparse TBM deposits; and Grade 2, presence of intense TBM deposits 13 (Figure 1).

Figure 1Different intensities of TBM deposits detected by electron microscopy in lupus nephritis patients.

…”

“…A previous study also indicated that some TBM deposits could be detected by electron microscopy (EM) but were not found by routine immunofluorescence (IF) assays, which emphasized the importance of EM examinations in the field. 13…”