Kidney Non Neoplastic: Practice Question

A 55 year old male presents with nephrotic range proteinuria. A renal biopsy is performed and diagnosed as membranous glomerulonephritis. What EM findings and autoantibody will most likely be present?
  1. PLA2R1, sub epithelial electron-dense deposits in a "spike and dome" pattern.
  2. APOL1, diffuse podocyte process effacement
  3. NELL-1, non-branching haphazardly arranged fibrils
  4. TSH7DA, sub epithelial "humps"
  5. None as this entity is not antibody related.
Show Answer and Explanations

PLA2R1, sub epithelial electron-dense deposits in a "spike and dome" pattern. — Correct answer

Correct. Phospholipase A2 receptor 1 (PLA2R1) is positive in 70-80% of cases of membranous glomerulonephritis. Electron microscopy typically shows sub epithelial electron-dense deposits in a "spike and dome" pattern.

APOL1, diffuse podocyte process effacement

Incorrect. APOL1 is associated with focal segmental glomerulosclerosis (FSGS). The podocyte effacement in FSGS is rather partial. Diffuse podocyte effacement is seen in minimal change disease.

NELL-1, non-branching haphazardly arranged fibrils

Incorrect. Neural epidermal growth factor-like 1 protein (NELL-1) is positive in approximately 15% of PLA2R negative membranous glomerulonephritis. Many entities in medical kidney are associated with fibrils. In general, by fibril size: - 7 to 12 nm thick fibrils: amyloid - 15-20 nm thick fibrils: fibrillary glomerulonephritis - >30 nm thick fibrils: immunotactoid glomerulopathy

TSH7DA, sub epithelial "humps"

Incorrect. Thrombospondin type 1 domain-containing 7A (THSD7A) is present in 2.6% of patients with membranous glomerulonephritis. Sub epithelial "humps" without GBM reaction (spikes) are seen in post streptococcal glomerulonephritis.

None as this entity is not antibody related.

Incorrect. Membranous glomerulonephritis is associated with autoantibodies to PLA2R1 (70-80%), NELL-1 (15%) or TSH7DA (2.6%) on podocytes and granular IgG deposition in immunofluorescence. Minimal change disease is not antibody mediated and shows diffuse podocyte effacement on electron microscopy.

Summary

Summary: Membranous glomerulonephritis is an autoimmune glomerular disease characterized by sub epithelial immune complex deposition with nephrotic range proteinuria and sub epithelial electron dense deposits in a "spike and dome" pattern in the GBM. It is associated with autoantibodies to PLA2R1 on podocytes in the majority of cases.
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