Glomerulonephritis for the ABIM
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Glomerulonephritis for the American Board of Internal Medicine Exam
- Definition:
- Glomerulonephritis (GN) refers to a group of kidney disorders characterized by inflammation of the glomeruli. It can present as an acute, subacute, or chronic disease, with manifestations ranging from asymptomatic hematuria to rapidly progressive renal failure. GN often involves immune-mediated injury to the glomerular capillary walls, resulting in compromised filtration.
- Etiology:
- Primary Glomerulonephritis: Diseases that primarily affect the kidneys.
- IgA Nephropathy (Berger's Disease): The most common cause of primary glomerulonephritis worldwide, characterized by mesangial IgA deposits. It typically presents with gross hematuria following an upper respiratory tract infection.
- Membranoproliferative Glomerulonephritis (MPGN): Can be idiopathic or secondary to infections (e.g., hepatitis C), with thickened capillary walls and a “tram-track” appearance on light microscopy due to immune complex deposition.
- Focal Segmental Glomerulosclerosis (FSGS): A common cause of nephrotic syndrome but can present with GN features, particularly in advanced stages.
- Secondary Glomerulonephritis: Diseases where GN is secondary to systemic conditions.
- Post-Streptococcal Glomerulonephritis (PSGN): Follows a group A Streptococcal infection (e.g., pharyngitis or impetigo). It presents with cola-colored urine, edema, and hypertension.
- Lupus Nephritis: Occurs as part of systemic lupus erythematosus (SLE) and classified into six classes, with proliferative types (class III and IV) leading to nephritic syndrome and renal impairment.
- Goodpasture Syndrome: A rare autoimmune disorder characterized by anti-glomerular basement membrane (anti-GBM) antibodies, causing pulmonary-renal syndrome (GN and hemoptysis).
- Granulomatosis with Polyangiitis (Wegener’s): An ANCA-associated vasculitis that affects small vessels in the kidney and respiratory tract. It presents with crescentic GN and respiratory symptoms (e.g., sinusitis, hemoptysis).
- Rapidly Progressive Glomerulonephritis (RPGN): A clinical syndrome associated with rapid decline in renal function (e.g., days to weeks) with histologic evidence of crescent formation in Bowman's space. RPGN can be caused by various underlying conditions, including ANCA vasculitis, Goodpasture syndrome, and lupus nephritis.
- Pathophysiology:
- Immune Complex Deposition: Immune complexes deposit in the glomeruli, triggering inflammation and complement activation. This is seen in diseases like post-infectious GN and lupus nephritis.
- Anti-GBM Antibodies: In Goodpasture syndrome, antibodies target the alpha-3 chain of type IV collagen in the glomerular and alveolar basement membranes, leading to renal and pulmonary damage.
- Pauci-Immune Mechanism: In ANCA-associated vasculitis, there are minimal or no immune deposits seen on immunofluorescence. ANCA antibodies activate neutrophils, causing small vessel vasculitis and glomerular inflammation.
- Complement-Mediated Damage: Overactivation of the complement system, as seen in diseases like MPGN, leads to glomerular injury due to membrane attack complex formation.
- Clinical Features:
- Nephritic Syndrome: The classic presentation of glomerulonephritis, characterized by hematuria, proteinuria, hypertension, and renal impairment.
- Hematuria: Typically gross (cola-colored or tea-colored urine) or microscopic hematuria with dysmorphic red blood cells and red cell casts in the urine.
- Proteinuria: Usually in the sub-nephrotic range (<3.5 g/day), though nephrotic range proteinuria can occur in severe cases or in advanced stages (e.g., FSGS).
- Hypertension: Due to fluid retention and activation of the renin-angiotensin system (RAS).
- Edema: Typically presents in the periorbital and dependent areas, resulting from salt and water retention.
- Oliguria: Reduced urine output is common in acute GN, indicating impaired renal function.
- Systemic Symptoms: Depending on the cause, systemic signs like fever, malaise, joint pains (as in lupus), or respiratory symptoms (as in Goodpasture syndrome or ANCA vasculitis) may be present.
- Diagnosis:
- Urinalysis: Shows hematuria with dysmorphic red blood cells and red cell casts, proteinuria (often sub-nephrotic), and sometimes white cell casts.
- Blood Tests:
- Serum Creatinine: Elevated in cases of renal impairment.
- Serologic Testing:
- Anti-Streptolysin O (ASO) Titers: Elevated in post-streptococcal GN.
- ANA: Positive in lupus nephritis.
- ANCA: Positive in ANCA-associated vasculitis (e.g., granulomatosis with polyangiitis).
- Anti-GBM Antibodies: Positive in Goodpasture syndrome.
- Complement Levels: Decreased in conditions like post-infectious GN, lupus nephritis, and MPGN.
- Renal Biopsy: Essential for definitive diagnosis, particularly in RPGN. Findings may include:
- Crescents: Seen in rapidly progressive GN.
- Immune Complex Deposits: Detected by immunofluorescence in post-infectious GN, lupus nephritis, and IgA nephropathy.
- Anti-GBM Antibodies: Linear staining pattern along the glomerular basement membrane in Goodpasture syndrome.
- Pauci-Immune Glomerulonephritis: Minimal staining on immunofluorescence, typical of ANCA-associated vasculitis.
- Complications:
- Acute Kidney Injury (AKI): Acute glomerular inflammation can lead to rapid decline in renal function, especially in RPGN.
- Chronic Kidney Disease (CKD): Recurrent or untreated GN can lead to glomerular scarring, progressive renal dysfunction, and eventually end-stage renal disease (ESRD).
- Hypertensive Crisis: Severe hypertension, as seen in GN, may lead to hypertensive emergencies if not properly managed.
- Pulmonary Hemorrhage: In Goodpasture syndrome or ANCA-associated vasculitis, life-threatening pulmonary hemorrhage can occur.
- Management:
- General Measures:
- Blood Pressure Control: ACE inhibitors or ARBs are the first-line agents for hypertension and to reduce proteinuria in glomerulonephritis.
- Diuretics: Used to manage fluid overload and edema.
- Immunosuppressive Therapy: For immune-mediated GN, corticosteroids are often the cornerstone of treatment, with additional agents like cyclophosphamide, rituximab, or mycophenolate mofetil depending on the underlying etiology.
- Specific Treatments:
- Post-Streptococcal GN: Supportive care, with management focused on blood pressure control and diuretics. Antibiotics are indicated to treat ongoing infections.
- Lupus Nephritis: Requires immunosuppressive therapy tailored to the class of lupus nephritis, typically involving corticosteroids, cyclophosphamide, or mycophenolate mofetil.
- Goodpasture Syndrome: Requires plasmapheresis to remove circulating anti-GBM antibodies, along with immunosuppression (corticosteroids, cyclophosphamide).
- ANCA-Associated Vasculitis: Treated with corticosteroids and cytotoxic agents (e.g., cyclophosphamide or rituximab). Plasmapheresis may be used in severe cases, such as those with pulmonary hemorrhage.
- Dialysis: May be necessary in patients with severe AKI or ESRD.
- Prognosis:
- The outcome depends on the underlying cause and timeliness of treatment. RPGN, if untreated, has a poor prognosis with progression to ESRD within weeks to months. Lupus nephritis and ANCA-associated vasculitis can lead to CKD if inadequately managed. IgA nephropathy has a more variable course, with some patients progressing to CKD, while others have a relatively benign prognosis.
Key Points
- Glomerulonephritis is characterized by hematuria, proteinuria, hypertension, and renal impairment.
- Primary causes include IgA nephropathy and MPGN, while secondary causes include lupus nephritis, post-streptococcal GN, and ANCA-associated vasculitis.
- Diagnosis relies on urinalysis, blood tests, and renal biopsy.
- Complications include AKI, CKD, and in some cases, life-threatening pulmonary hemorrhage.
- Management includes blood pressure control, immunosuppressive therapy, and plasmapheresis in certain autoimmune forms.
- Prognosis varies depending on the cause, with RPGN being the most rapidly progressive form of GN.