TY - JOUR
T1 - Characteristics of patients with coexisting DNAJB9-associated fibrillary glomerulonephritis and IgA nephropathy
AU - Said, Samar M.
AU - Rocha, Alejandro Best
AU - Valeri, Anthony M.
AU - Sandid, Mohamad
AU - Ray, Anhisekh Sinha
AU - Fidler, Mary E.
AU - Alexander, Mariam Priya
AU - Larsen, Christopher P.
AU - Nasr, Samih H.
N1 - Publisher Copyright:
© The Author(s) 2020.
PY - 2021/6/1
Y1 - 2021/6/1
N2 - Background. Coexistence of fibrillary glomerulonephritis (FGN) and immunoglobulin A (IgA) nephropathy (IgAN) in the same kidney biopsy (FGN-IgAN) is rare, and the clinicopathologic characteristics and outcome of this dual glomerulopathy are unknown. Methods. In this study, 20 patients with FGN-IgAN were studied and their characteristics were compared with 40 FGN and 40 IgAN control patients. Results. Concurrent IgAN was present in 1.8% of 847 consecutive FGN cases and was the second most common concurrent glomerulopathy after diabetic nephropathy. FGN-IgAN patients were overwhelmingly White (94%) and contrary to FGN patients were predominantly (60%) males. Compared with IgAN patients, FGN-IgAN patients were older, had higher proteinuria, a higher incidence of renal insufficiency, and a lower incidence of microhematuria and gross hematuria at diagnosis. Six (30%) patients had malignancy, autoimmune disease or hepatitis C infection, but none had a secondary cause of IgAN or clinical features of Henoch-Schonlein purpura. Histologically, all cases exhibited smudgy glomerular staining for immunoglobulin G and DnaJ homolog subfamily B member 9 (DNAJB9) with corresponding fibrillary deposits and granular mesangial staining for IgA with corresponding mesangial granular electron-dense deposits. On follow-up (median 27 months), 10 of 18 (56%) FGN-IgAN patients progressed to end-stage kidney disease (ESKD), including 5 who subsequently died. Serum creatinine at diagnosis was a poor predictor of renal survival. The proportion of patients reaching ESKD or died was higher in FGN-IgAN than in IgAN. The median Kaplan-Meier ESKD-free survival time was 44 months for FGN-IgAN, which was shorter than IgAN (unable to compute, P =0.013) and FGN (107 months, P=0.048). Conclusions. FGN-IgAN is very rare, with clinical presentation and demographics closer to FGN than IgAN. Prognosis is guarded with a median renal survival of 3.6 years. The diagnosis of this dual glomerulopathy requires careful evaluation of immunofluorescence findings, and electron microscopy or DNAJB9 immunohistochemistry.
AB - Background. Coexistence of fibrillary glomerulonephritis (FGN) and immunoglobulin A (IgA) nephropathy (IgAN) in the same kidney biopsy (FGN-IgAN) is rare, and the clinicopathologic characteristics and outcome of this dual glomerulopathy are unknown. Methods. In this study, 20 patients with FGN-IgAN were studied and their characteristics were compared with 40 FGN and 40 IgAN control patients. Results. Concurrent IgAN was present in 1.8% of 847 consecutive FGN cases and was the second most common concurrent glomerulopathy after diabetic nephropathy. FGN-IgAN patients were overwhelmingly White (94%) and contrary to FGN patients were predominantly (60%) males. Compared with IgAN patients, FGN-IgAN patients were older, had higher proteinuria, a higher incidence of renal insufficiency, and a lower incidence of microhematuria and gross hematuria at diagnosis. Six (30%) patients had malignancy, autoimmune disease or hepatitis C infection, but none had a secondary cause of IgAN or clinical features of Henoch-Schonlein purpura. Histologically, all cases exhibited smudgy glomerular staining for immunoglobulin G and DnaJ homolog subfamily B member 9 (DNAJB9) with corresponding fibrillary deposits and granular mesangial staining for IgA with corresponding mesangial granular electron-dense deposits. On follow-up (median 27 months), 10 of 18 (56%) FGN-IgAN patients progressed to end-stage kidney disease (ESKD), including 5 who subsequently died. Serum creatinine at diagnosis was a poor predictor of renal survival. The proportion of patients reaching ESKD or died was higher in FGN-IgAN than in IgAN. The median Kaplan-Meier ESKD-free survival time was 44 months for FGN-IgAN, which was shorter than IgAN (unable to compute, P =0.013) and FGN (107 months, P=0.048). Conclusions. FGN-IgAN is very rare, with clinical presentation and demographics closer to FGN than IgAN. Prognosis is guarded with a median renal survival of 3.6 years. The diagnosis of this dual glomerulopathy requires careful evaluation of immunofluorescence findings, and electron microscopy or DNAJB9 immunohistochemistry.
KW - DNAJB9
KW - IgA nephropathy
KW - electron microscopy
KW - fibrillary deposits
KW - fibrillary glomerulonephritis
KW - glomerulonephritis
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U2 - 10.1093/ckj/sfaa205
DO - 10.1093/ckj/sfaa205
M3 - Article
AN - SCOPUS:85138656735
SN - 2048-8505
VL - 14
SP - 1681
EP - 1690
JO - Clinical Kidney Journal
JF - Clinical Kidney Journal
IS - 6
ER -