WHEN THE SPIKES ARE NOT MEMBRANOUS: AN UNUSUAL PRESENTATION OF FIBRILLARY GLOMERULONEPHRITIS

Introduction:

Fibrillary glomerulonephritis (FGN) is a rare glomerular disease with a poor prognosis, accounting for approximately 1% of all native kidney biopsies. On kidney biopsy, it is characterized by randomly arranged, non-branching fibrils (10-30 nm in diameter), and is composed of IgG and C3. DNAJB9 is an immunohistochemical stain that is a sensitive and specific marker of FGN. 

Methods:

A 59-year-old female with seizure disorder controlled off anti-epileptics presented to nephrology clinic for evaluation of nephrotic range proteinuria. She reported a two-month history of frothy urine, but denied other symptoms including periorbital edema, facial swelling, or lower extremity edema. She denied use of prescription or over-the-counter medications or supplements.

Results:

Initial workup with her primary care provider revealed normal renal function with a creatinine of 0.55 mg/dL, mild hypoalbuminemia of 3.4 g/dL, 1+ proteinuria on urinalysis, and spot urine albumin-to-creatinine ratio of 2616 mg/g. An extensive autoimmune, infectious, and paraproteinemia workup, including serum electrophoresis, ANCA studies, hepatitis B and C serologies, HIV, and RPR, was negative and C3 and C4 were within normal limits. Total cholesterol was elevated, for which she was started on statin therapy. Kidney ultrasound was unremarkable. Repeat urine studies at our office revealed nephrotic range proteinuria with a spot urine protein-to-creatinine ratio of 5.38 mg/mg and urine albumin-to-creatinine ratio of 4255 mg/g. Kidney biopsy showed spikes along the glomerular capillary basement on light microscopy and randomly arranged subepithelial fibrils consistent with FGN on electron microscopy. Immunohistochemistry for DNAJB9 was positive, confirming the diagnosis. 

Figure 1. Spikes along the glomerular capillary basement membranes are seen on light microscopy, mimicking the pattern of injury most commonly associated with membranous glomerulonephritis.

Figure 2. Randomly arranged fibrils consistent with fibrillary glomerulonephritis. Fibrils are seen in a subepithelial distribution on electron microscopy.

Figure 3. Immunohistochemistry for DNAJB9 is positive within the deposits along glomerular capillary loops, confirming a diagnosis of fibrillary glomerulonephritis.

Conclusions:

The “spikes” on light microscopy are classically seen with membranous glomerulonephritis and serve as a mimicker in this case of FGN. High index of suspicion for rare glomerular diseases must be maintained for consideration of treatment options and prognostication. 

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.