Glomerulonephritis for USMLE Step 2

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Glomerulonephritis for the USMLE Step 2 Exam

Glomerulonephritis (GN) is an inflammatory condition affecting the glomeruli of the kidneys, often causing hematuria, proteinuria, hypertension, and renal impairment. It can be classified as primary (originating in the kidney) or secondary (due to systemic diseases).

Primary Glomerulonephritis:
IgA Nephropathy (Berger’s Disease): The most common primary GN, especially in younger adults. It often presents with episodic gross hematuria following respiratory or gastrointestinal infections. Pathology shows IgA deposition in the mesangium.
Membranoproliferative Glomerulonephritis (MPGN): Immune complex deposition thickens the glomerular basement membrane, giving a “tram-track” appearance on microscopy. It can be idiopathic or associated with chronic infections (e.g., hepatitis C).
Secondary Glomerulonephritis:
Post-Streptococcal Glomerulonephritis (PSGN): Occurs after group A Streptococcal infections, typically in children. Presents with cola-colored urine, edema, and hypertension 1-3 weeks after infection.
Lupus Nephritis: A severe form of GN associated with systemic lupus erythematosus (SLE). Immune complexes deposit in the glomeruli, leading to various patterns of glomerular injury. Diffuse proliferative lupus nephritis (Class IV) is the most severe.
Goodpasture Syndrome: Caused by anti-glomerular basement membrane (anti-GBM) antibodies, which attack the glomerular and alveolar basement membranes, causing GN and pulmonary hemorrhage.
Granulomatosis with Polyangiitis (Wegener’s): ANCA-associated vasculitis that affects the kidneys and respiratory tract. Crescentic GN is common, along with systemic symptoms like sinusitis and hemoptysis.

Immune Complex Deposition: Immune complexes deposit in the glomeruli, causing inflammation and complement activation, as seen in PSGN, lupus nephritis, and IgA nephropathy.
Anti-GBM Antibodies: In Goodpasture syndrome, antibodies attack the glomerular basement membrane, causing severe glomerular damage.
ANCA-Associated Vasculitis: Minimal immune deposits are found on biopsy, but ANCA antibodies activate neutrophils, leading to small vessel vasculitis and glomerular injury.

Hematuria: Commonly presents as gross hematuria (cola-colored urine) or microscopic hematuria with dysmorphic red blood cells and red cell casts.
Proteinuria: Usually sub-nephrotic (<3.5 g/day) but can occasionally reach nephrotic levels.
Hypertension: Caused by sodium and water retention, commonly seen in PSGN and lupus nephritis.
Edema: Periorbital and dependent edema are typical, resulting from fluid retention.
Oliguria: Reduced urine output in severe cases, indicating acute kidney injury (AKI).
Systemic Symptoms: Fever, malaise, and joint pain are common in lupus nephritis, while respiratory symptoms like hemoptysis may accompany Goodpasture syndrome and ANCA vasculitis.

Urinalysis: Reveals hematuria, dysmorphic red blood cells, red cell casts, and proteinuria.
Blood Tests:
Serum Creatinine: Elevated in cases of 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: Critical for diagnosing the underlying cause and severity of GN. Biopsy findings may include immune complex deposits, crescent formation (RPGN), or linear anti-GBM antibody staining.

Supportive Care: Includes blood pressure control with ACE inhibitors or ARBs, diuretics to manage fluid overload, and dietary sodium restriction.
Immunosuppressive Therapy: Corticosteroids are the cornerstone of treatment for immune-mediated GN. Cytotoxic agents (e.g., cyclophosphamide) or biologics (e.g., rituximab) may be required for severe cases such as lupus nephritis or ANCA-associated vasculitis.
Plasmapheresis: Used in Goodpasture syndrome and some cases of ANCA vasculitis to remove circulating pathogenic antibodies.
Dialysis: May be necessary in cases of severe AKI or end-stage renal disease (ESRD).

Key Points

Glomerulonephritis presents with hematuria, proteinuria, hypertension, and edema.
Primary causes include IgA nephropathy and MPGN; secondary causes include PSGN, lupus nephritis, and ANCA vasculitis.
Diagnosis involves urinalysis, serologic markers (ASO, ANA, ANCA, anti-GBM), and renal biopsy.
Management includes blood pressure control, immunosuppressive therapy, plasmapheresis in autoimmune cases, and dialysis if severe renal impairment occurs.