Renal · Year 2 · from Renal

Case 2: Membranous Nephropathy with Renal Vein Thrombosis

Patient Presentation

Demographics: 52-year-old male

Chief Complaint: Leg swelling and sudden left flank pain

History of Present Illness: The patient has had progressive lower extremity edema for 2 months. Today he developed sudden onset severe left flank pain radiating to the groin. He also notes foamy urine and a 10-pound weight gain. He has no history of kidney disease. He takes no medications and has no known malignancy.

Physical Examination:

  • Blood pressure: 138/88 mmHg
  • Heart rate: 102 bpm
  • General: Uncomfortable, moderate distress
  • Lungs: Clear
  • Abdomen: Left-sided tenderness, no masses
  • Extremities: 3+ bilateral pitting edema
  • Left flank: Tenderness to palpation

Workup and Results

Laboratory Studies:

  • Creatinine: 1.6 mg/dL
  • Albumin: 1.8 g/dL
  • Total cholesterol: 420 mg/dL
  • 24-hour urine protein: 9.2 g
  • Urinalysis: 4+ protein, trace blood, oval fat bodies
  • C3 and C4: Normal
  • Anti-PLA2R antibody: Positive (185 RU/mL)
  • ANA, hepatitis serologies: Negative

CT Abdomen with Contrast:

  • Left renal vein thrombosis with extension into IVC
  • Enlarged left kidney

Renal Biopsy:

  • Light microscopy: Thickened capillary walls
  • Immunofluorescence: Granular IgG and C3 along GBM
  • Electron microscopy: Subepithelial deposits with spike and dome pattern

Clinical Image

Renal biopsy demonstrating membranous nephropathy with characteristic "spike and dome" pattern on electron microscopy, showing subepithelial electron-dense deposits with intervening basement membrane projections.

Diagnosis

Primary Membranous Nephropathy with Renal Vein Thrombosis

  • Anti-PLA2R positive (present in ~70% of primary MN)
  • Nephrotic syndrome with heavy proteinuria
  • Classic thrombotic complication

Discussion

This case demonstrates membranous nephropathy and its complications:

  • Anti-PLA2R Antibodies: The lecture describes how anti-PLA2R antibodies are found in approximately 70% of primary membranous nephropathy cases. A positive test can obviate biopsy in typical presentations.
  • Spike and Dome Pattern: Characteristic EM finding as subepithelial deposits form and GBM projects around them. Immunofluorescence shows granular IgG staining.
  • Thromboembolism Risk: The lecture emphasizes that membranous nephropathy carries particularly high thrombosis risk, especially renal vein thrombosis. This is due to urinary loss of anticoagulant proteins (antithrombin III) and increased hepatic synthesis of procoagulant factors.
  • Secondary Causes: Always exclude malignancy (especially in older patients), hepatitis B, lupus, and medications (NSAIDs, gold).

Treatment Plan

  1. Immediate Anticoagulation:
  • Heparin transitioning to warfarin
  • Continue until nephrotic syndrome resolves
  • Prophylactic anticoagulation if albumin <2.5 g/dL
  1. RAAS Blockade:
  • ACE inhibitor for proteinuria reduction
  1. Immunosuppression (for high-risk features):
  • Rituximab (increasingly first-line)
  • OR cyclophosphamide plus corticosteroids
  • Monitor anti-PLA2R levels (correlate with disease activity)
  1. Cancer Screening:
  • Age-appropriate malignancy workup
  • CT chest/abdomen/pelvis
  • Colonoscopy if indicated

Teaching Points

  1. Anti-PLA2R antibodies are highly specific for primary membranous nephropathy
  2. Membranous nephropathy has the highest thrombosis risk among glomerular diseases
  3. Albumin <2.5 g/dL warrants consideration of prophylactic anticoagulation
  4. Always exclude secondary causes including malignancy

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