Fibrillary Glomerulonephritis and Apolipoprotein A-IV Amyloidosis: A Rare Dual Pathology Diagnosed by Mass Spectrometry and DNAJB9 Immunohistochemistry

Fibrillary glomerulonephritis is a rare cause of proteinuric kidney disease characterized by Congo red-negative fibrillary deposits and typically shows DNAJB9 positivity on immunohistochemistry. Amyloidosis is defined by Congo red positivity and can be typed by laser microdissection-tandem mass spectrometry when routine studies are inconclusive. We report the case of a 64-year-old man with proteinuria and declining kidney function whose kidney biopsy showed DNAJB9-positive fibrillary glomerulonephritis in glomeruli, but Congo red-positive deposits confined to the medulla were DNAJB9 negative. Laser microdissection-tandem mass spectrometry of the medullary deposits identified apolipoprotein A-IV amyloidosis, establishing concurrent fibrillary glomerulonephritis and apolipoprotein A-IV amyloidosis in the same biopsy. Apolipoprotein A-IV amyloidosis is often medullary predominant and, in rare hereditary forms related to autosomal dominant <i>APOA4</i> variants, may have implications for family members. Although apolipoprotein A-IV amyloidosis has been reported in cardiac amyloidosis, transthoracic echocardiography and cardiac magnetic resonance imaging showed no evidence of cardiac amyloid involvement in this patient. This case highlights that discordant staining patterns with DNAJB9-positive fibrillary glomerulonephritis alongside Congo red positivity in DNAJB9-negative areas should prompt consideration of dual pathology and targeted mass spectrometry to accurately type deposits and guide management.