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Updated: Jan 16, 2026

Analyses of Proteinuria, Renal Infiltration of Leukocytes, and Renal Deposition of Proteins in Lupus-prone MRL/lpr Mice
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Analyses of Proteinuria, Renal Infiltration of Leukocytes, and Renal Deposition of Proteins in Lupus-prone MRL/lpr Mice

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Isolated C3 hypocomplementemia as an early predictor of chronic kidney disease in lupus nephritis

Simeone Andrulli1, Lucio Manenti2, Francesco Reggiani3

  • 1Associazione Italiana Ricercare per Curare ODV ETS (AIRpC), Lecco, Italy.

Frontiers in Immunology
|September 29, 2025
PubMed

Insights

Low C3 levels six months after lupus nephritis diagnosis indicate a higher risk of long-term kidney damage and death. Monitoring C3 complement levels can help predict lupus nephritis outcomes.

Area of Science:

  • Nephrology
  • Immunology
  • Rheumatology

Background:

  • The long-term impact of complement system activation on renal survival in lupus nephritis (LN) is not fully understood.
  • Existing research suggests complement plays a role, but long-term data are scarce.

Purpose of the Study:

  • To investigate the influence of complement levels on long-term renal outcomes in lupus nephritis patients.
  • To determine if isolated C3 hypocomplementemia (i-LowC3) at six months post-biopsy predicts risks of chronic kidney disease (CKD), end-stage kidney disease (ESKD), or death.

Main Methods:

  • A multicenter, observational, retrospective study of 445 lupus nephritis patients.
  • Patients were categorized into i-LowC3 (low C3, normal C4) and control groups at six months post-kidney biopsy.
  • Median follow-up was 4.9 years, analyzing renal outcomes including CKD, ESKD, and mortality.

Main Results:

  • Isolated C3 hypocomplementemia (i-LowC3) was associated with a twofold increased risk of poor renal outcomes (CKD, ESKD, death) compared to controls (P < 0.001).
  • Patients with i-LowC3 exhibited lower survival rates for all analyzed outcomes.
  • Increasing C3 levels within the first six months correlated with a reduced risk of CKD and death.

Conclusions:

  • Serum C3 level trajectory in the first six months post-diagnosis is a significant predictor of long-term renal prognosis in lupus nephritis.
  • Isolated C3 hypocomplementemia serves as a valuable, cost-effective biomarker for guiding early treatment strategies in LN patients.
Abstract

Keywords:
CKDESKDcomplementimmunosuppressionlupusproteinuria

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