In a child with acute glomerulonephritis, when does the complement component C3 level typically return to normal?

C3 Complement Normalization in Acute Post-Streptococcal Glomerulonephritis

In children with acute post-streptococcal glomerulonephritis, C3 complement levels typically return to normal within 6 to 8 weeks (answer C), though normalization may extend to 8–12 weeks in uncomplicated cases. 1

Expected Timeline for C3 Normalization

• C3 levels normalize by 8–12 weeks in the vast majority of uncomplicated PSGN cases, with complete normalization typically occurring within this window 1, 2
• The decrease in C3 is found in more than 90% of PSGN cases and represents a cardinal diagnostic feature 3
• C3 depression typically appears earlier than the rise in anti-streptolysin O (ASO) titers, making it a valuable early diagnostic marker 3

Clinical Significance of Prolonged Hypocomplementemia

Persistently low C3 beyond 12 weeks warrants kidney biopsy to exclude alternative diagnoses, particularly C3 glomerulopathy or other complement-mediated diseases 1, 2

• Approximately 26% of PSGN patients may demonstrate hypocomplementemia persisting beyond 8 weeks, yet still have biopsy-confirmed PSGN with eventual complete recovery 4
• Prolonged hypocomplementemia (>8 weeks) with resolving clinical features does not automatically exclude PSGN, and biopsy may be deferred if clinical improvement is evident 4
• However, if C3 remains low beyond 12 weeks, proceed to kidney biopsy to distinguish PSGN from primary C3 glomerulopathy, which requires different management 1, 2

Complement Activation Patterns in PSGN

• Both classical and alternative complement pathways are activated in the early disease phase, with low C1q and/or C4 levels suggesting classical pathway involvement 5
• Alternative pathway activation predominates in sustaining C3 depression beyond the initial phase 5
• Transient C3 nephritic factor (C3NeF) IgG autoantibody activity mediates early hypocomplementemia and disappears within 1–4 months as C3 normalizes 6
• Complement activation through the alternative pathway may precede clinical onset of nephritis by days 7

Monitoring Algorithm

Follow this structured approach for C3 monitoring:

• Measure C3 at diagnosis and every 2–4 weeks until normalization 1
• Monitor concurrent clinical parameters: serum creatinine, urinalysis with microscopy, and urine protein-to-creatinine ratio 2
• At 8 weeks: If C3 remains low but clinical improvement continues, continue observation with repeat testing 4
• At 12 weeks: If C3 has not normalized, perform kidney biopsy and comprehensive complement workup (C3 nephritic factor, factor H/I/B) to exclude C3 glomerulopathy 1, 2

Common Pitfalls to Avoid

• Do not assume alternative diagnosis prematurely if C3 remains low at 8 weeks but clinical features are improving—up to one-quarter of PSGN patients show prolonged hypocomplementemia 4
• Do not delay biopsy beyond 12 weeks of persistent hypocomplementemia, as this threshold distinguishes self-limited PSGN from chronic complement-mediated disease requiring immunosuppression 1, 2
• Measure both C3 and C4 levels, as isolated low C3 with normal C4 supports alternative pathway activation typical of PSGN, whereas combined low C3 and C4 suggests lupus or cryoglobulinemia 2