Glomerulonephritis for USMLE Step 1
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Glomerulonephritis for the USMLE Step 1 Exam
- Definition:
- Glomerulonephritis (GN) refers to a group of disorders causing inflammation of the glomeruli, the small filtering units of the kidney. It often presents with hematuria, proteinuria, hypertension, and varying degrees of renal impairment.
- Etiology:
- Primary Glomerulonephritis:
- IgA Nephropathy (Berger’s Disease): The most common primary GN worldwide. It typically presents with episodes of hematuria following upper respiratory tract infections. Immunofluorescence shows IgA deposits in the mesangium.
- Membranoproliferative Glomerulonephritis (MPGN): Characterized by immune complex deposition leading to glomerular capillary wall thickening and a “tram-track” appearance on light microscopy. It may be primary or secondary to infections (e.g., hepatitis C).
- Focal Segmental Glomerulosclerosis (FSGS): Primarily associated with nephrotic syndrome but can manifest with mixed nephritic-nephrotic features in more advanced disease.
- Secondary Glomerulonephritis:
- Post-Streptococcal Glomerulonephritis (PSGN): Occurs 1-3 weeks after group A Streptococcal infection (e.g., pharyngitis, impetigo). Presents with hematuria (cola-colored urine), edema, and hypertension.
- Lupus Nephritis: Seen in systemic lupus erythematosus (SLE). Immune complex deposition leads to glomerular damage, with diffuse proliferative lupus nephritis (Class IV) being the most severe form of GN in lupus patients.
- Goodpasture Syndrome: An autoimmune disorder characterized by anti-glomerular basement membrane (anti-GBM) antibodies, leading to renal failure and pulmonary hemorrhage (hemoptysis).
- Granulomatosis with Polyangiitis (Wegener’s): ANCA-associated vasculitis affecting the kidneys and respiratory system. Crescentic GN is a hallmark, along with systemic symptoms like sinusitis and hemoptysis.
- Pathophysiology:
- Immune Complex Deposition: Circulating immune complexes deposit in the glomeruli, triggering complement activation and inflammation, seen in PSGN, lupus nephritis, and IgA nephropathy.
- Anti-GBM Antibodies: In Goodpasture syndrome, antibodies attack the glomerular basement membrane, causing glomerular injury.
- ANCA-Associated Vasculitis: Minimal immune deposits, but ANCA antibodies activate neutrophils, leading to small vessel vasculitis and glomerular damage.
- Clinical Features:
- Hematuria: Commonly gross (cola- or tea-colored urine) or microscopic, often with dysmorphic red blood cells and red cell casts in the urine.
- Proteinuria: Usually sub-nephrotic (<3.5 g/day), but can be nephrotic range in diseases like FSGS.
- Hypertension: Results from fluid retention and activation of the renin-angiotensin-aldosterone system (RAAS).
- Edema: Periorbital and dependent edema are common due to sodium and water retention.
- Oliguria: Reduced urine output, indicating significant renal impairment in severe GN cases.
- Systemic Symptoms: Fever, malaise, and joint pains may accompany GN in conditions like lupus or ANCA-associated vasculitis.
- Diagnosis:
- Urinalysis: Reveals hematuria with dysmorphic red blood cells, red cell casts, and proteinuria.
- Blood Tests:
- Serum Creatinine: Elevated in cases of renal impairment.
- Complement Levels: Low in post-infectious GN, lupus nephritis, and MPGN.
- 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.
- Renal Biopsy: Confirms diagnosis, showing immune complex deposits, crescent formation, or linear staining for anti-GBM antibodies.
- Management:
- Supportive Care: Includes blood pressure control (ACE inhibitors or ARBs) and diuretics to manage hypertension and fluid overload.
- Immunosuppressive Therapy: Corticosteroids are the cornerstone of treatment, especially in immune-mediated GN. Cyclophosphamide or rituximab may be used for severe forms like lupus nephritis or ANCA-associated vasculitis.
- Plasmapheresis: Used in Goodpasture syndrome to remove circulating anti-GBM antibodies.
- Dialysis: Necessary in severe cases of acute kidney injury (AKI) or end-stage renal disease (ESRD).
Key Points
- Glomerulonephritis presents with hematuria, proteinuria, hypertension, and varying degrees of renal impairment.
- Causes include primary glomerulonephritis (IgA nephropathy, MPGN) and secondary glomerulonephritis (PSGN, lupus nephritis, ANCA vasculitis).
- Diagnosis is based on urinalysis, serologic markers (e.g., ASO, ANA, ANCA, anti-GBM), and renal biopsy for definitive identification.
- Management focuses on blood pressure control, immunosuppressive therapy, and plasmapheresis in autoimmune forms.