Immunoglobulin-Negative DNAJB9-Associated Fibrillary Glomerulonephritis: A Report of 9 Cases

Am J Kidney Dis. 2021 Mar;77(3):454-458. doi: 10.1053/j.ajkd.2020.04.015. Epub 2020 Jul 23.

Abstract

Fibrillary glomerulonephritis (FGN) was previously defined by glomerular deposition of haphazardly oriented fibrils that stain with antisera to immunoglobulins but do not stain with Congo red. We report what is to our knowledge the first series of immunoglobulin-negative FGN, consisting of 9 adults (7 women and 2 men) with a mean age at diagnosis of 66 years. Patients presented with proteinuria (100%; mean protein excretion, 3g/d), hematuria (100%), and elevated serum creatinine level (100%). Comorbid conditions included carcinoma in 3 and hepatitis C virus infection in 2; no patient had hypocomplementemia or monoclonal gammopathy. Histologically, glomeruli were positive for DNAJB9, showed mostly mild mesangial hypercellularity and/or sclerosis, and were negative for immunoglobulins by immunofluorescence on frozen and paraffin tissue. Ultrastructurally, randomly oriented fibrils measuring 13 to 20nm in diameter were seen intermingling with mesangial matrix in all and infiltrating glomerular basement membranes in 5. On follow-up (mean duration, 21 months), 2 had disease remission, 4 had persistently elevated serum creatinine levels and proteinuria, and 3 required kidney replacement therapy. Thus, rare cases of FGN are not associated with glomerular immunoglobulin deposition, and the diagnosis of FGN in these cases can be confirmed by DNAJB9 immunostaining. Pathogenesis remains to be elucidated.

Keywords: DnaJ homolog subfamily B member 9 (DNAJB9); Fibrillary glomerulonephritis (FGN); IgG-negative fibrillary GN; case report; electron microscopy; fibrillary deposits; kidney biopsy; light microscopy; mesangial sclerosis; negative immunofluorescence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Comorbidity
  • Creatinine / metabolism
  • Female
  • Glomerular Basement Membrane / ultrastructure
  • Glomerular Mesangium / ultrastructure
  • Glomerulonephritis / epidemiology
  • Glomerulonephritis / metabolism*
  • Glomerulonephritis / pathology
  • Glomerulonephritis / therapy
  • HSP40 Heat-Shock Proteins / metabolism*
  • Hematuria / metabolism
  • Humans
  • Immunoglobulin G / metabolism*
  • Immunosuppressive Agents / therapeutic use
  • Liver Cirrhosis / epidemiology
  • Male
  • Membrane Proteins / metabolism*
  • Microscopy, Electron
  • Middle Aged
  • Molecular Chaperones / metabolism*
  • Neoplasms / epidemiology
  • Proteinuria / metabolism
  • Pulmonary Disease, Chronic Obstructive / epidemiology
  • Renal Replacement Therapy
  • Sclerosis

Substances

  • DNAJB9 protein, human
  • HSP40 Heat-Shock Proteins
  • Immunoglobulin G
  • Immunosuppressive Agents
  • Membrane Proteins
  • Molecular Chaperones
  • Creatinine