What is the most likely diagnosis for a patient with heavy proteinuria, hypoalbuminemia, and edema, who has membranous glomerulonephritis (thickening of the glomerular basement membrane) following hepatitis B infection?

Nephrotic Syndrome in a Patient with Membranous Glomerulonephritis Following Hepatitis B Infection

The urinalysis results showing 4+ protein, oval fat bodies, fatty casts, and fat droplets are diagnostic of nephrotic syndrome, specifically membranous nephropathy (MN) secondary to hepatitis B infection, which is causing thickening of the glomerular basement membrane due to immune complex deposition.

Diagnosis Explanation

A. Most Probable Disorder

The urinalysis findings represent classic nephrotic syndrome with the following key features:

• Heavy proteinuria (4+)
• Lipiduria (oval fat bodies, fatty casts, moderate fat droplets)
• RBC presence (20-30 RBCs/hpf)

These findings, particularly the combination of heavy proteinuria and lipiduria, are pathognomonic for nephrotic syndrome in a patient with membranous glomerulonephritis following hepatitis B infection 1, 2.

B. Primary Structures Causing Glomerular Basement Membrane Thickening

In membranous glomerulonephritis, the thickening of the glomerular basement membrane occurs due to:

• Subepithelial immune complex deposits between the podocyte foot processes and the glomerular basement membrane
• Complement activation following immune complex formation
• Basement membrane matrix expansion in response to injury

In hepatitis B-associated membranous nephropathy specifically, the thickening results from deposition of immune complexes containing hepatitis B antigens (particularly HBeAg) and their corresponding antibodies 3.

C. Three Abnormal Blood Chemistry Tests

The three markedly abnormal blood chemistry tests in nephrotic syndrome are:

1. Hypoalbuminemia (serum albumin <3.0 g/dL)
2. Hyperlipidemia (elevated total cholesterol, LDL, and triglycerides)
3. Elevated urinary protein-to-creatinine ratio (>3.5 g/g)

Clinical Management

Risk Assessment

According to KDIGO guidelines, this patient should be evaluated for risk of progressive kidney disease 3. Risk factors include:

• Heavy proteinuria (4+ on urinalysis)
• Presence of edema
• Secondary cause (hepatitis B infection)

Treatment Approach

1. Treat underlying hepatitis B infection:

   • Antiviral therapy is the first-line treatment for hepatitis B-associated membranous nephropathy

2. Immunosuppressive therapy:

   • For patients with persistent nephrotic syndrome despite antiviral therapy, immunosuppressive options include:
     • Rituximab
     • Cyclophosphamide with alternate month glucocorticoids for 6 months
     • Calcineurin inhibitor (CNI)-based therapy for ≥6 months 3

3. Supportive therapy:

   • Prednisone for edema management and proteinuria reduction 4
   • ACE inhibitors or ARBs to reduce proteinuria
   • Diuretics for edema control
   • Dietary sodium restriction (<2g/day)

Complications to Monitor

1. Thromboembolism: Patients with membranous nephropathy have a particularly high risk of venous thrombosis due to:

   • Loss of anticoagulant proteins in urine
   • Increased procoagulant factors
   • Hypoalbuminemia 5

2. Infections: Due to urinary loss of immunoglobulins and complement factors

3. Acute kidney injury: Can occur from severe hypovolemia or interstitial nephritis

Important Considerations

• Serological testing: Anti-PLA2R antibody testing should be considered, as its presence or absence can help distinguish primary from secondary MN 3

• Kidney biopsy findings: In hepatitis B-associated MN, immunofluorescence typically shows granular deposits of IgG, C3, and hepatitis B antigens along the glomerular basement membrane

• Treatment monitoring: Serial measurements of proteinuria, serum albumin, and in cases of primary MN, anti-PLA2R antibody titers help assess response to therapy

• Thrombosis prophylaxis: Consider anticoagulation in patients with severe hypoalbuminemia (<2.5 g/dL) and other risk factors for thrombosis 6

The management of membranous nephropathy secondary to hepatitis B requires a coordinated approach targeting both the viral infection and the immune-mediated glomerular injury to prevent progression to chronic kidney disease.