Glomerulonephritis for USMLE Step 3
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Glomerulonephritis for the USMLE Step 3 Exam
- Definition:
- Glomerulonephritis (GN) is an inflammatory disorder affecting the glomeruli, often resulting in hematuria, proteinuria, edema, and renal impairment. GN can be classified as primary (originating within the kidney) or secondary (associated with systemic diseases).
- Etiology:
- Primary Glomerulonephritis:
- IgA Nephropathy (Berger’s Disease): The most common primary GN, presenting with episodic gross hematuria following upper respiratory or gastrointestinal infections. Characterized by IgA deposition in the mesangium on immunofluorescence.
- Membranoproliferative Glomerulonephritis (MPGN): Characterized by immune complex deposition, leading to thickened capillary walls and a “tram-track” appearance on light microscopy. Can be idiopathic or secondary to chronic infections (e.g., hepatitis C).
- Secondary Glomerulonephritis:
- Post-Streptococcal Glomerulonephritis (PSGN): Occurs after group A Streptococcal infection (e.g., pharyngitis, impetigo), with symptoms of cola-colored urine, edema, and hypertension. It commonly affects children 1-3 weeks post-infection.
- Lupus Nephritis: Associated with systemic lupus erythematosus (SLE). Diffuse proliferative lupus nephritis (Class IV) is the most severe form, characterized by extensive immune complex deposition.
- Goodpasture Syndrome: A rare autoimmune disorder where anti-glomerular basement membrane (anti-GBM) antibodies attack both renal and alveolar basement membranes, leading to GN and pulmonary hemorrhage.
- Granulomatosis with Polyangiitis (Wegener’s): ANCA-associated vasculitis that affects the kidneys and respiratory tract, presenting with crescentic GN and systemic symptoms like sinusitis and hemoptysis.
- Pathophysiology:
- Immune Complex Deposition: Seen in PSGN, lupus nephritis, and IgA nephropathy, immune complexes deposit in the glomeruli, triggering complement activation and inflammation.
- Anti-GBM Antibodies: In Goodpasture syndrome, antibodies target the glomerular and alveolar basement membranes, causing damage to both.
- ANCA-Associated Vasculitis: ANCA antibodies activate neutrophils, causing small vessel vasculitis with minimal immune deposits on biopsy.
- Clinical Features:
- Hematuria: Gross (cola- or tea-colored urine) or microscopic hematuria with dysmorphic red blood cells and red cell casts is a hallmark of GN.
- Proteinuria: Typically sub-nephrotic (<3.5 g/day), though nephrotic range proteinuria can be seen in advanced disease.
- Hypertension: Common due to sodium and fluid retention.
- Edema: Periorbital and dependent edema due to fluid overload.
- Oliguria: Reduced urine output, suggesting acute kidney injury (AKI).
- Systemic Symptoms: Lupus nephritis may present with fever, arthralgia, and rash, while Goodpasture syndrome and ANCA vasculitis may involve hemoptysis and respiratory symptoms.
- Diagnosis:
- Urinalysis: Reveals hematuria, dysmorphic red blood cells, red cell casts, and proteinuria.
- Blood Tests:
- Serum Creatinine: Elevated in renal impairment.
- Serologic Markers:
- Anti-Streptolysin O (ASO) Titers: Elevated in PSGN.
- ANA: Positive in lupus nephritis.
- ANCA: Positive in ANCA-associated vasculitis.
- Anti-GBM Antibodies: Positive in Goodpasture syndrome.
- Complement Levels: Low in PSGN, lupus nephritis, and MPGN.
- Renal Biopsy: Crucial for identifying the underlying cause. Findings may include immune complex deposition, crescent formation, or linear staining for anti-GBM antibodies.
- Management:
- Supportive Care: Blood pressure control (ACE inhibitors, ARBs) and diuretics for fluid overload.
- Immunosuppressive Therapy: Corticosteroids are the mainstay, often combined with cyclophosphamide or rituximab in severe forms like lupus nephritis or ANCA vasculitis.
- Plasmapheresis: Used in Goodpasture syndrome and some cases of ANCA-associated vasculitis to remove circulating antibodies.
- Dialysis: May be required in severe cases of AKI or end-stage renal disease (ESRD).
Key Points
- Glomerulonephritis presents with hematuria, proteinuria, hypertension, and renal dysfunction.
- Primary causes include IgA nephropathy and MPGN; secondary causes include PSGN, lupus nephritis, and ANCA vasculitis.
- Diagnosis relies on urinalysis, serologic markers (ASO, ANA, ANCA, anti-GBM), and renal biopsy.
- Management involves blood pressure control, immunosuppressive therapy, plasmapheresis, and dialysis for severe renal impairment.