TY - JOUR
T1 - Immunoglobulin-Negative DNAJB9-Associated Fibrillary Glomerulonephritis
T2 - A Report of 9 Cases
AU - Said, Samar M.
AU - Rocha, Alejandro Best
AU - Royal, Virginie
AU - Valeri, Anthony M.
AU - Larsen, Christopher P.
AU - Theis, Jason D.
AU - Vrana, Julie A.
AU - McPhail, Ellen D.
AU - Bandi, Lalitha
AU - Safabakhsh, Saied
AU - Barnes, Chadwick
AU - Cornell, Lynn D.
AU - Fidler, Mary E.
AU - Alexander, Mariam Priya
AU - Leung, Nelson
AU - Nasr, Samih H.
N1 - Publisher Copyright:
© 2020 National Kidney Foundation, Inc.
PY - 2021/3
Y1 - 2021/3
N2 - 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.
AB - 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.
KW - DnaJ homolog subfamily B member 9 (DNAJB9)
KW - Fibrillary glomerulonephritis (FGN)
KW - IgG-negative fibrillary GN
KW - case report
KW - electron microscopy
KW - fibrillary deposits
KW - kidney biopsy
KW - light microscopy
KW - mesangial sclerosis
KW - negative immunofluorescence
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U2 - 10.1053/j.ajkd.2020.04.015
DO - 10.1053/j.ajkd.2020.04.015
M3 - Article
C2 - 32711071
AN - SCOPUS:85090119734
SN - 0272-6386
VL - 77
SP - 454
EP - 458
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 3
ER -