Renal · Glomerulonephritis
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IgA nephropathy is the most common primary glomerulonephritis worldwide and classically presents as synpharyngitic hematuria, although asymptomatic microscopic hematuria is also common.
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 reference 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 receive maximally tolerated ACE inhibitors or ARBs plus an SGLT2 inhibitor to slow disease progression.
IgA vasculitis (formerly Henoch-Schönlein purpura) 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 reference standard.
Treatment
First-line is optimized supportive care — maximally tolerated ACE inhibitor or ARB plus an SGLT2 inhibitor; sparsentan may replace the RAS blocker. Per KDIGO 2025, patients at risk of progression (proteinuria ≥0.5 g/day) should start IgAN-directed therapy concurrently rather than after a supportive-care run-in, preferably a 9-month course of targeted-release budesonide (Nefecon) over systemic corticosteroids.
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 and lectin complement pathways, 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 reference 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, with an SGLT2 inhibitor added for patients at risk of progressive kidney function loss. Sparsentan, a dual endothelin–angiotensin receptor antagonist, may be used in place of (not in addition to) the RAS blocker. Per KDIGO 2025, patients at risk of progressive kidney function loss (proteinuria ≥0.5 g/day) should begin IgAN-directed therapy concurrently with supportive care rather than after a 90-day run-in, preferably a 9-month course of targeted-release budesonide (Nefecon); a reduced-dose systemic glucocorticoid regimen with antimicrobial prophylaxis is an alternative where Nefecon is unavailable. The treatment goal is proteinuria <0.5 g/day (ideally <0.3 g/day). Immunosuppressants are reserved for rapidly progressive cases.
Prognosis
Long-term monitoring of proteinuria and creatinine is recommended. 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
IgA vasculitis (formerly Henoch-Schönlein purpura): systemic vasculitis with palpable purpura and arthralgias
Minimal change disease: presents with nephrotic syndrome, not hematuria