Final Diagnosis -- Fibrillary Glomerulonephritis


FINAL DIAGNOSIS

Fibrillary glomerulonephritis

DISCUSSION

Fibrillary glomerulonephritis (FGN) was first described in 1977 [1] and is a rare form of glomerulonephritis with the incidence of less than 1% in native renal biopsies [2-5]. The signs and symptoms of FGN include hematuria and proteinuria, kidney insufficiency and high blood pressure. Up to 50% of the patients progress to end-stage renal disease within 2-4 years [6]. FGN is known to be associated with hepatitis C virus infection, malignancy and autoimmune disease.

The diagnosis of FGN can be established by renal biopsy, and electron microscopy findings demonstrates randomly arranged nonbranching fibrils with a mean diameter of 18-20 nm (range 10-30 nm) deposited in mesangial areas and along GBM. The fibrils are mostly confined to glomeruli and stain by immunofluorescence for IgG, C3, kappa, and lambda [6].

Histologically, renal biopsies demonstrate diffuse mesangial expansion by eosinophilic material which is negative for Congo red stain. Other histologic patterns include mesangial proliferation, membranoproliferative glomerulonephritis, crescents (~25%), and segmental and/or global glomerular scarring [6]. In 2018, the Mayo Clinic [7] and the University of Washington [8] groups identified DNAJB9, one of the most abundant proteins in the FGN glomerular proteome. DNAJB9 is present in the normal kidney at low levels in podocytes, renal tubular epithelial cells, and endothelial and mesangial cells. The only disease associated with DNAJB9 extracellular deposition is FGN. DNAJB9 is not seen in other forms of glomerulonephritis or amyloidosis. DNAJB9 co-localizes with IgG and components of the classic complement pathway in glomeruli. The sensitivity and specificity of DNAJB9 staining for the diagnosis of FGN are known to be 98% and 99%, respectively [9]. The DNAJB9 stain also helps to establish the diagnosis of FGN when electron microscopy is not readily available.

The differential diagnoses for FGN include amyloidosis and immunotactoid glomerulopathy. The Congo red positivity with apple-green birefringence under polarized light and the thickness of the fibrils (8-12 nm) help to differentiate amyloidosis from FGN (Figure 4). Immunotactoid glomerulopathy can be distinguished by their thicker fibrils (30-50 nm) and the presence of a microtubular appearance with a hollow core [6].

Figure 4. Electron Microscopic Findings of Amyloidosis (UPMC case) showing Non-branching, haphazardly arranged fibrillar material ranging in thickness from 6.32 to 14.9 nm (11.23 +/- 2.58 nm)

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REFERENCES

  1. Nephron. 1977;18:301-308
  2. Clinical and pathologic features of fibrillary glomerulonephritis. Kidney Int. 1992;42:1401-1407.
  3. Morphologic and clinical features of fibrillary glomerulonephritis versus immunotactoid glomerulopathy. Am J Kidney Dis. 1993;22:367-377
  4. Fibrillary and immunotactoid glomerulonephritis: distinct entities with different clinical and pathologic features. Kidney Int. 2003;63:1450-1461.
  5. Fibrillary glomerulonephritis: a report of 66 cases from a single institution. Clin J Am Soc Nephrol. 2011;6:775-784.
  6. Diagnostic Pathology Kidney Diseases, 1st edition, Section 2: Glomerular disease, Idiopathic fibrillary glomerulopathies, Lippincott Williams & Wilkins. 2011:259-263.
  7. DnaJ heat shock protein family B member 9 is a novel biomarker for fibrillary GN. J Am Soc Nephrol. 2018;29:51-56.
  8. DnaJ homolog subfamily B member 9 is a putative autoantigen in fibrillary GN. J Am Soc Nephrol. 2018;29:231-239.
  9. Kidney Int Rep. 2019 Apr 29;4(7):917-922.

Contributed by Yujung Jung, MD and Sheldon Bastacky, MD




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