14.2 Glomerulonephritis & Hematuria
Key Takeaways
- Post-streptococcal glomerulonephritis (PSGN) follows strep infection by 1-2 weeks (pharyngitis) or 3-6 weeks (impetigo), with a low C3 that should normalize within 6-8 weeks.
- IgA nephropathy classically causes synpharyngitic gross hematuria within 24-72 hours of an upper respiratory infection, with a normal C3 — the key feature distinguishing it from PSGN.
- Glomerular hematuria produces brown or tea-colored urine, dysmorphic red blood cells, RBC casts, and accompanying proteinuria; non-glomerular hematuria does not.
- Idiopathic hypercalciuria and thin basement membrane nephropathy are the most common causes of isolated asymptomatic microscopic hematuria in children.
- Alport syndrome presents with hematuria, sensorineural hearing loss, and ocular abnormalities, with a family history of male relatives progressing to renal failure.
Glomerulonephritis & Hematuria
The distinction between post-streptococcal glomerulonephritis and IgA nephropathy — by infection-to-hematuria timing and complement level — is a recurring single-best-answer theme on the Arab Board written paper, alongside structured hematuria work-up questions.
Post-Streptococcal Glomerulonephritis (PSGN)
Post-streptococcal glomerulonephritis (PSGN) is an immune-complex-mediated nephritis that follows infection with nephritogenic strains of Group A Streptococcus (Streptococcus pyogenes). Unlike minimal change disease, PSGN is a nephritic, not nephrotic, process — the primary problem is glomerular inflammation causing hematuria and reduced glomerular filtration rate, not primarily a leaky filtration barrier.
Timing is diagnostic. There is a latency period between the streptococcal infection and the onset of renal disease, reflecting the time needed for immune complexes to form and deposit in the glomeruli:
| Preceding infection | Typical latency to PSGN |
|---|---|
| Pharyngitis (throat) | About 1-2 weeks (average around 10 days) |
| Impetigo (skin) | About 3-6 weeks |
Peak incidence is between ages 5 and 12; PSGN is uncommon under age 3. Presentation follows the classic nephritic picture: gross, tea- or cola-colored hematuria, periorbital edema, hypertension from sodium and water retention, and oliguria. Proteinuria is usually present but rarely reaches nephrotic range. Severe hypertension can occasionally cause hypertensive encephalopathy, a genuine emergency.
Key labs: C3 is low because of activation of the alternative complement pathway, while C4 is usually normal. Evidence of the antecedent streptococcal infection is documented with an elevated ASO (anti-streptolysin O) titer, which is more useful after pharyngitis, or an elevated anti-DNase B titer, which is more sensitive after skin infection since the ASO response to impetigo is often blunted. A throat or skin culture is not required for diagnosis. C3 should normalize within 6-8 weeks; a persistently low C3 beyond that window should prompt referral for biopsy to rule out membranoproliferative glomerulonephritis or another chronic complement-mediated disease. Treatment is supportive — sodium and fluid restriction, diuretics, and antihypertensives as needed — and the pediatric prognosis is excellent, with the great majority of children recovering fully.
Exam trap: do not confuse the expected, self-limited course of PSGN with rapidly progressive glomerulonephritis (RPGN). If a child with an apparent nephritic illness instead shows a steadily rising creatinine over days to weeks, oliguria that fails to improve, or crescents on biopsy, think beyond routine PSGN toward a crescentic process (which can rarely complicate severe PSGN, or point to a distinct vasculitic or anti-GBM disease) and escalate the work-up accordingly rather than assuming the benign PSGN trajectory will hold.
IgA Nephropathy vs. PSGN: The Timing Distinction
IgA nephropathy (Berger disease) is the most common cause of chronic glomerulonephritis worldwide, and it is a frequent examiner favorite specifically because of how it is distinguished from PSGN: by timing relative to the preceding infection.
| Feature | PSGN | IgA nephropathy |
|---|---|---|
| Timing of hematuria relative to infection | Delayed: 1-2 weeks after pharyngitis, or 3-6 weeks after skin infection | Synpharyngitic: gross hematuria within 24-72 hours of URI/pharyngitis onset, essentially concurrent |
| Serum C3 | Low | Normal |
| Course | Usually a single self-limited episode | Recurrent episodes of gross hematuria over months to years |
| Long-term risk | Low in children | Can progress to chronic kidney disease |
The distinction worth internalizing: PSGN hematuria appears weeks after the sore throat has resolved, while IgA nephropathy hematuria appears together with the sore throat. Definitive diagnosis of IgA nephropathy requires a renal biopsy showing mesangial IgA deposits, but a normal C3 with synpharyngitic timing should already move it to the top of the differential on a written exam. IgA vasculitis (Henoch-Schönlein purpura) is a related, IgA-mediated systemic small-vessel vasculitis presenting with palpable purpura over the lower extremities and buttocks, arthralgia, abdominal pain, and nephritis; its renal lesion is histologically identical to isolated IgA nephropathy.
Approach to Hematuria: Glomerular vs. Non-Glomerular
Hematuria is generally defined as more than 5 red blood cells per high-power field on microscopy. The first branch point in any hematuria question is whether the bleeding source is glomerular or non-glomerular (lower urinary tract):
| Feature | Glomerular | Non-glomerular |
|---|---|---|
| Urine color | Brown, tea- or cola-colored | Red or pink, may contain clots |
| RBC morphology | Dysmorphic RBCs (acanthocytes) | Normal-shaped RBCs |
| Casts | RBC casts present | Absent |
| Associated proteinuria | Often present | Usually absent |
| Typical causes | PSGN, IgA nephropathy, Alport syndrome | UTI, hypercalciuria, trauma, stones, coagulopathy |
For a child with isolated microscopic hematuria found incidentally, for example on a school physical, with no proteinuria, casts, or hypertension, the two most common benign explanations are idiopathic hypercalciuria, screened with a spot urine calcium:creatinine ratio, and thin basement membrane nephropathy (benign familial hematuria). Initial workup includes urinalysis with microscopy, urine culture, blood pressure, renal function testing, and C3/C4; ASO and anti-DNase B titers are added if PSGN is suspected. A family history of renal failure and deafness in male relatives should raise concern for Alport syndrome, most commonly X-linked (COL4A5), which classically presents with the triad of hematuria, sensorineural hearing loss, and ocular abnormalities such as anterior lenticonus, and can progress to end-stage renal disease.
Worked scenario: A 6-year-old girl develops tea-colored urine and facial swelling about 10 days after recovering from strep pharyngitis. Blood pressure is 130/85 mmHg, C3 is low, and ASO titer is elevated. Supportive care with salt and fluid restriction is appropriate; C3 should be rechecked in 6-8 weeks to confirm normalization.
A 7-year-old develops cola-colored urine, periorbital edema, and hypertension 12 days after a sore throat. Labs show a low C3. Which diagnosis is most likely?
Which laboratory finding best distinguishes IgA nephropathy from post-streptococcal glomerulonephritis?
A 10-year-old develops gross hematuria on the same day he develops a sore throat and low-grade fever. C3 is normal. This timing pattern is most characteristic of which condition?
Which urinary finding is most suggestive of a glomerular source of hematuria?
A previously healthy 8-year-old boy is found to have isolated asymptomatic microscopic hematuria on a routine school physical, with no proteinuria, casts, or hypertension. What is the most appropriate next step?