✅ Model Answer:
• Diagnosis: Membranoproliferative glomerulonephritis (MPGN) type I – secondary to hepatitis C.
• Evidence: Nephrotic-range proteinuria (P/C 2.8), hypoalbuminemia (2.5), edema, low C3 (classic pathway), normal C4, positive hepatitis C serology.
• Next step: Treat hepatitis C with direct-acting antivirals (sofosbuvir, ledipasvir). Start ACE inhibitor/ARB for proteinuria. Renal biopsy for confirmation (subendothelial immune deposits, mesangial proliferation). Monitor renal function and proteinuria.

✅ Model Answer:
• Definition: MPGN is a glomerular disease characterized by mesangial proliferation and capillary wall thickening ("split" basement membrane).
• Type I MPGN: Subendothelial immune deposits, classic complement pathway activation (low C3, normal C4).
• Pathophysiology in hepatitis C: Chronic hepatitis C infection leads to the formation of cryoglobulins (type II mixed cryoglobulinemia) – immune complexes deposit in the glomerular mesangium and subendothelial space → complement activation → glomerular injury.
• Other causes: Hepatitis B, lupus, chronic infections, monoclonal gammopathies.
• Renal biopsy: Light microscopy: mesangial proliferation, "tram-track" appearance (due to GBM duplication). Immunofluorescence: IgG, IgM, C3 along capillary loops.

✅ Model Answer:
• Classic features:
- Nephrotic syndrome: Edema, proteinuria (P/C >2.0), hypoalbuminemia.
- Low C3 (classic pathway – usually with normal C4 in type I).
- Hematuria: Microscopic or gross (RBCs, RBC casts).
- Hypertension.
- Renal insufficiency (elevated creatinine).
- Secondary causes: Hepatitis C (cryoglobulinemia), hepatitis B, lupus, chronic infections.
• Other: May present with nephritic-nephrotic picture (hematuria + proteinuria + HTN + renal insufficiency).
• Age: Can occur at any age; often presents in children with both nephrotic and nephritic features.

✅ Model Answer:
• Urine P/C ratio: Nephrotic-range or subnephrotic.
• Serum complement: Low C3, normal C4 (type I). Low C3 and C4 (type II – dense deposit disease).
• Serum creatinine/eGFR: Assess renal function.
• Hepatitis B/C serology, HIV: To rule out secondary causes.
• ANA, dsDNA: To rule out lupus.
• Cryoglobulins: Positive in hepatitis C-associated MPGN.
• Renal biopsy: Gold standard – shows mesangial proliferation, GBM duplication ("tram-track"), subendothelial deposits. Immunofluorescence: IgG, IgM, C3 deposition.
• Electron microscopy: Subendothelial deposits, mesangial interposition.

✅ Model Answer:
• Treat the underlying cause:
- Hepatitis C: Direct-acting antivirals (sofosbuvir, ledipasvir, glecaprevir/pibrentasvir) – cure HCV, leading to resolution of MPGN in many cases.
- Hepatitis B: Antiviral therapy (entecavir, tenofovir).
- Lupus: Immunosuppression.
• Renal supportive therapy:
- ACE inhibitor/ARB: To reduce proteinuria and BP.
- Diuretics: For edema.
- Sodium restriction.
- Statins: For hyperlipidemia.
• Immunosuppression (if severe or refractory):
- Corticosteroids: May be used for severe nephrotic syndrome (in addition to antiviral therapy).
- Rituximab: For refractory cryoglobulinemic MPGN.
• Monitor: Proteinuria, BP, creatinine, HCV RNA (to assess response).

✅ Model Answer:
• Chronic kidney disease (CKD): Progressive renal impairment (30-50% progress to ESKD within 10 years).
• Nephrotic syndrome: Edema, infections, thromboembolism.
• Hypertension.
• Thromboembolism: Due to nephrotic syndrome (renal vein thrombosis).
• Infections: Pneumococcal peritonitis (if nephrotic syndrome is severe).
• Recurrence: Can recur after kidney transplantation (especially in type II).
• Cirrhosis: If hepatitis C progresses to liver disease.

✅ Model Answer:
• Prognosis:
- Improved with direct-acting antivirals (HCV cure → MPGN resolution).
- If HCV is cured: Proteinuria and renal function often improve.
- If untreated: 30-50% progress to ESKD within 10 years.
- Children: May have a better prognosis than adults.
- Renal transplantation: Disease can recur (less common in HCV-associated MPGN if cured).
• Long-term follow-up:
- Monitor proteinuria, BP, creatinine.
- Monitor HCV RNA (to confirm cure).
- Monitor for liver disease.
- Vaccinations: Pneumococcal, varicella (if nephrotic syndrome).
- Genetic counseling if familial MPGN (rare).

✅ Model Answer:
• MPGN type I:
- Complement: Low C3, normal C4 (classic pathway).
- Pathology: Subendothelial immune deposits.
- Causes: Hepatitis C, hepatitis B, lupus, chronic infections.
- Treatment: Treat underlying cause + ACE inhibitor/ARB.
- Prognosis: Variable; better with treatment of underlying cause.
• MPGN type II (Dense deposit disease):
- Complement: Low C3, low C4 (alternative pathway – C3 nephritic factor).
- Pathology: Intramembranous dense deposits (on EM).
- Causes: C3 nephritic factor (autoantibody), genetic complement abnormalities.
- Treatment: Immunosuppression (corticosteroids, mycophenolate, eculizumab).
- Prognosis: Worse; high risk of ESKD and recurrence post-transplant.