DNAJB9-Associated Fibrillary Glomerulonephritis and Immunoglobulin A Nephropathy – A Rare Combination

Dear Editor,

A 67-year-old gentleman presented to us for evaluation of incidentally detected renal dysfunction. He had systemic hypertension for 10 years and was recently detected to have diabetes. The blood pressure was 150/90 mm of Hg and had no evidence of target organ damage related to diabetes or hypertension.

Urinalysis showed 2+ albuminuria with 10–16 red blood corpuscles/high-power field. The urine spot protein–creatinine ratio was 3.1 and serum creatinine was 1.6 mg/dl. C3 and C4 levels were normal. Serological testing for hepatitis B surface antigen, hepatitis C antibody, antinuclear antibody, antineutrophilic cytoplasmic antibodies, anti-glomerular basement membrane antibodies, serum cryoglobulins, and human immunodeficiency virus antibody were all negative. Serum protein electrophoresis with immunofixation was negative for monoclonal protein.

Renal biopsy showed histopathologic findings consistent with fibrillary glomerulonephritis and immunoglobulin A nephropathy dual glomerulopathy (in light, immunofluorescence, and electron microscopy), and all glomeruli stained positive for DNA-J heat-shock protein family member B9 (DNAJB9) [Figure 1].

Close

Figure 1:

Renal biopsy showing mesangioproliferative pattern of glomerular injury on light microscopy (a–d). Immunofluorescence microscopy showing smudge positivity of IgG along the capillary loops with intensely positive IgA and C3 over mesangium (×400) (e–h). Glomeruli were intensely positive for DNAJB9 immunohistochemical stain (×600) (i and j). Electron microscopy confirmed nonbranching linear fibrils on capillary loops and mesangium, along with electron-dense deposits consistent (arrows) with IgA over mesangium (k and l) DNAJB9 = DNA-J heat-shock protein family member B9.

Export to PPT

His renin-angiotensin-aldosterone system blockade was enhanced to 80 mg daily of telmisartan. At 6 months follow-up, he is asymptomatic, and his blood pressure is well controlled with a serum creatinine of 1.4 mg/dl and urine spot protein–creatinine ratio of 1.6. He is advised to remain on close follow-up.

Coexistent FGN–IgAN glomerulopathy is an extremely rare form of glomerular disease.^1,2 FGN–IgAN has a similar clinical presentation as FGN and is associated with infections (hepatitis C), autoimmune diseases, or malignancy in 30% of cases.³ In our patient, workup for secondary causes of FGN was negative. The discovery of DNAJB9 and immunohistochemical staining for DNAJB9 now make it possible to diagnose FGN even in the absence of ultrastructural evaluation.³ Our report highlights a patient with idiopathic FGN–IgAN dual glomerulopathy, an extremely rare glomerular disease. To our knowledge, this condition has not been reported before from the Indian subcontinent.