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

Samar M. Said, Alejandro Best Rocha, Virginie Royal, Anthony M. Valeri, Christopher P. Larsen, Jason D. Theis, Julie A. Vrana, Ellen D. McPhail, Lalitha Bandi, Saied Safabakhsh, Chadwick Barnes, Lynn D. Cornell, Mary E. Fidler, Mariam Priya Alexander, Nelson Leung, Samih H. Nasr

Research output: Contribution to journalArticlepeer-review

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, 3 g/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 20 nm 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.

Original languageEnglish (US)
Pages (from-to)454-458
Number of pages5
JournalAmerican Journal of Kidney Diseases
Volume77
Issue number3
DOIs
StatePublished - Mar 2021

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

ASJC Scopus subject areas

  • Nephrology

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