Renal · Glomerulonephritis
The facts most likely to be tested
IgA nephropathy is the most common cause of glomerulonephritis worldwide and typically presents as synpharyngitic hematuria.
The classic clinical presentation is gross hematuria occurring within 1–3 days of an upper respiratory tract infection.
The pathophysiology involves the deposition of IgA immune complexes in the mesangium of the glomerulus.
Renal biopsy is the gold standard for diagnosis, revealing mesangial hypercellularity and IgA deposits on immunofluorescence.
IgA nephropathy is distinguished from post-streptococcal glomerulonephritis by the timing of hematuria, which occurs weeks after infection in the latter.
Patients with persistent proteinuria, hypertension, or elevated creatinine should be treated with ACE inhibitors or ARBs to slow disease progression.
Henoch-Schönlein purpura (IgA vasculitis) is considered the systemic form of IgA nephropathy, characterized by palpable purpura, abdominal pain, and arthralgias.
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A 22-year-old male presents to the clinic with dark, tea-colored urine. He reports that the symptoms began yesterday, two days after the onset of a sore throat and nasal congestion. He has no history of skin rashes, joint pain, or recent travel. Physical examination reveals a blood pressure of 135/85 mmHg and no peripheral edema. Urinalysis shows dysmorphic red blood cells and red cell casts.
What is the most likely diagnosis?
IgA nephropathy (Berger disease)
The patient's presentation of hematuria occurring 1-3 days after an upper respiratory infection is classic for synpharyngitic hematuria, which is the hallmark of IgA nephropathy.
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Etiology / Epidemiology
Most common glomerulonephritis worldwide; typically affects young males following a URI.
Clinical Manifestations
Synpharyngitic hematuria is the hallmark; gross hematuria occurs within 1-2 days of infection.
Diagnosis
Renal biopsy with immunofluorescence showing IgA deposits in the mesangium is the gold standard.
Treatment
ACE inhibitors or ARBs are first-line; corticosteroids reserved for high-risk patients.
Prognosis
20-40% progress to end-stage renal disease (ESRD) within 20 years.
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Epidemiology & Etiology
Predominantly affects young adult males (2nd-3rd decade). Often triggered by mucosal infections, specifically synpharyngitic (respiratory or GI) episodes. It is the most common cause of primary glomerulonephritis globally.
Pertinent Anatomy
Pathology is localized to the glomerular mesangium. The deposition of immune complexes triggers local inflammation and subsequent glomerular injury.
Pathophysiology
Circulating galactose-deficient IgA1 immune complexes deposit in the mesangium. This activates the alternative complement pathway, leading to mesangial cell proliferation and matrix expansion. Chronic inflammation results in focal segmental glomerulosclerosis.
Clinical Manifestations
Classic presentation is synpharyngitic hematuria, where gross hematuria appears 24-48 hours after a URI. Patients may present with flank pain or asymptomatic microscopic hematuria. Hypertension and edema are common signs of progressive renal decline.
Diagnosis
Renal biopsy is the gold standard, revealing IgA mesangial deposits on immunofluorescence. Urinalysis typically shows dysmorphic RBCs and RBC casts. Serum IgA levels are often elevated but are not diagnostic.
Treatment
Management focuses on blood pressure control using ACE inhibitors or ARBs to reduce proteinuria. Corticosteroids are indicated for patients with persistent proteinuria >1g/day despite maximal supportive care. Immunosuppressants are reserved for rapidly progressive cases.
Prognosis
Long-term monitoring of proteinuria and creatinine is mandatory. 20-40% of patients progress to ESRD over two decades. Risk of progression is highest in patients with persistent proteinuria and hypertension.
Differential Diagnosis
Post-streptococcal GN: occurs 1-3 weeks post-infection with low C3
Alport syndrome: associated with sensorineural hearing loss and family history
Thin basement membrane disease: usually benign, non-progressive hematuria
Henoch-Schönlein purpura: systemic vasculitis with palpable purpura and arthralgias
Minimal change disease: presents with nephrotic syndrome, not hematuria