When does serum complement C3 return to normal in a child with acute post‑streptococcal glomerulonephritis?

When Does C3 Return to Normal in Acute Post-Streptococcal Glomerulonephritis?

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

Expected Timeline for C3 Normalization

• C3 levels normalize within 8-12 weeks in the vast majority of uncomplicated PSGN cases, with complete normalization typically occurring by this timeframe 1
• The most commonly cited range in clinical guidelines is 6 to 8 weeks, which represents the expected recovery period for most pediatric patients 1
• C3 complement depression is a hallmark finding at presentation and serves as a key diagnostic criterion for PSGN 1

Clinical Significance of Persistent Hypocomplementemia

If C3 remains low beyond 12 weeks, this is a critical red flag requiring kidney biopsy to exclude C3 glomerulopathy (C3GN) rather than self-resolving PSGN 1, 2

Key monitoring points:

• Persistently low C3 beyond week 12 warrants kidney biopsy according to KDIGO 2021 guidelines to distinguish PSGN from complement C3 glomerulonephritis 1
• Some patients (approximately 26% in one prospective study) may have prolonged hypocomplementemia beyond 8 weeks but still have PSGN with gradual clinical improvement 3
• However, prolonged hypocomplementemia beyond 12 weeks should not be assumed to be benign PSGN without further investigation 1, 2

Important Clinical Pitfalls

Do not dismiss prolonged low C3 as "just slow recovery":

• While research shows that some PSGN patients can have hypocomplementemia lasting beyond 8 weeks with eventual complete recovery 3, clinical guidelines emphasize that C3 remaining low beyond 12 weeks requires biopsy to exclude alternative diagnoses 1
• C3 nephritic factor (C3NeF) autoantibody activity has been documented in PSGN patients and may contribute to transient hypocomplementemia, typically becoming undetectable within 1-4 months after C3 normalization 4
• Genetic complement abnormalities (such as CFHR5 deficiency) can predispose patients to persistent kidney disease after streptococcal infection, manifesting as C3 glomerulopathy rather than typical self-limited PSGN 5

Practical Management Algorithm

At diagnosis:

• Document baseline C3 level (expect it to be low) 1
• Confirm recent streptococcal infection with ASO, anti-DNAse B, or anti-hyaluronidase antibodies 1

At 6-8 weeks:

• Recheck C3 level—most patients will have normalized by this point 1
• If C3 is normalizing and clinical features are improving, continue observation 1

At 12 weeks:

• If C3 remains low, proceed immediately to kidney biopsy and comprehensive complement workup (including C3NeF, factor H/I/B, genetic screening) 1, 2
• This distinguishes chronic C3 glomerulopathy from lingering post-infectious changes 1

The correct answer to the question is C: 6 to 8 weeks (or up to 8-12 weeks), but any child whose C3 has not normalized by 12 weeks requires kidney biopsy to exclude alternative diagnoses.