Diagnose This (August 3, 2020)

What is your leading diagnosis when seeing this interesting IgG staining pattern by IF?

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The immunofluorescence shows a glomerulus with a very characteristic “smudgy” pattern of staining with IgG within the mesangium and along the capillary loops characteristic of Fibrillary Glomerulopathy. Fibrillary GN is an extremely rare disease, seen in <1% of native kidney biopsies and is caused by the deposition of fibrillar deposits of immunoglobulin within the mesangium with extension into the glomerular capillary loops. By electron microscopy, the fibrils are characterized as non-branching, randomly arranged, and have an average diameter of approximately 20 nm (range: 10-30 nm). In addition to identifying fibrils by electron microscopy, an immunohistochemical stain described by Nasr et al., DNAJB9, is typically positive as it shows a 98% sensitivity and greater than 99% specificity in these cases. Regarding outcome, approximately 40-50% of all patients will progress to ESRD within four years. Unfortunately, the disease also carries a high recurrence rate within renal allografts (up to 50%). Nasr et al. also found in their case series that approximately 17% of patients with Fibrillary GN had a concomitant positive SPEP/UPEP, necessitating the need to further rule out a dysproteinemia in these patients. For additional information on this fascinating disease, see references below.

References:

Nasr et al. DNAJB9 Is a Specific Immunohistochemical Marker for Fibrillary Glomerulonephritis. Kidney Int Rep (2018) 3, 56-64.

Nasr et al. Fibrillary Glomerulonephritis: A Report of 66 Cases from a Single Institution. Clin J Am Soc Nephrol (2011) 6, 775-784.