Fibrillary Glomerulonephritis: An Update

Abstract

Fibrillary glomerulonephritis (FGN) is a rare proliferative form of glomerular disease characterized by randomly oriented fibrillar deposits with a mean diameter of 20 nm. By immunofluorescence (IF), the deposits stain for IgG, C3, and κ and λ light chains, suggesting that the fibrils may be composed of antigen-antibody immune complexes. A recent major advance in our understanding of the pathogenesis of FGN resulted from the discovery that a major component of the fibrils is DNA-J heat-shock protein family member B9 (DNAJB9), and immunohistochemical staining for DNAJB9 now makes it possible to diagnose FGN in the absence of ultrastructural evaluation. FGN has a poor prognosis, treatment options are currently limited, and transplant recurrence is not uncommon.

Keywords: DNAJB9; fibrillary glomerulonephritis.

Figure 1

Renal biopsy findings in fibrillary glomerulonephritis (FGN). (a) A glomerulus exhibits global mesangial proliferation with expansion of the mesangial matrix by amorphous eosinophil material that corresponds with the fibrillary deposits and also involves and mildly expands the peripheral capillary walls of the glomerular basement membrane (GBM). In addition to mesangial proliferation, there is evidence of endocapillary proliferation with focal infiltrating mononuclear leukocytes (hematoxylin and eosin; original magnification ×400). (b) The Jones methenamine silver stain highlights the eosinophilic deposits that expand the mesangial matrix and GBMs, and also demonstrates segmental GBM duplication with cellular interposition (“membranoproliferative features”; original magnification ×400). (c) Immunofluorescence staining for IgG reveals intense global mesangial and glomerular capillary wall–ill-defined, smudged positivity. Identical staining for C3, κ, and λ was noted (original magnification ×400). (d) Ultrastructural evaluation demonstrates abundant fibrils that permeate and expand the GBM and also are seen in the mesangial matrix. Overlying visceral epithelial cells exhibit complete foot process effacement (original magnification ×12,000). (e) At higher magnification, the fibrils are randomly oriented with a mean diameter of 20 nm (original magnification ×60,000). (f) Immunohistochemical staining for DNA-J heat-shock protein family member B9 is strongly positive in the mesangial matrix and GBMs, which is the same distribution as the randomly oriented fibrils in this biopsy showing FGN (original magnification ×400).