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Long-Term Renal Survival in Antineutrophil Cytoplasmic Antibody-Associated Glomerulonephritis With Complement C3
Rina Oba1, Go Kanzaki1, Takaya Sasaki1
1Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
Insights
Glomerular C3 deposition in antineutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN) indicates a poorer prognosis. Patients with C3 deposits experienced worse kidney and overall survival rates, highlighting its significance in ANCA-GN progression.
Area of Science:
- Nephrology
- Immunology
- Pathology
Background:
- Complement activation is increasingly recognized as a key factor in the development of antineutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN).
- The prognostic value of glomerular C3 deposition in ANCA-GN requires further investigation.
Purpose of the Study:
- To evaluate the clinicopathologic significance of glomerular C3 deposition in patients with ANCA-GN.
- To determine the prognostic impact of C3 deposition on renal and overall survival in ANCA-GN.
Main Methods:
- Retrospective analysis of 142 ANCA-GN patients from Japanese hospitals (2004-2020).
- Glomerular C3 deposition identified via direct immunofluorescence (IF) (staining ≥1+).
- Composite endpoints: 30% eGFR reduction, ESKD, or death; compared outcomes between C3-positive and C3-negative groups.
Main Results:
- C3 deposition was present in 39.4% of ANCA-GN kidney biopsies.
- Patients with C3 deposition showed lower serum C3 levels and significantly worse 5-year event-free survival (log-rank P=0.002).
- Multivariable analysis confirmed C3 deposition as a significant predictor of adverse outcomes (aHR=2.02, P=0.008), independent of other factors.
Conclusions:
- Glomerular C3 deposition on immunofluorescence is a significant indicator of worse renal outcomes in ANCA-GN.
- ANCA-GN patients with C3 deposition exhibit poorer overall survival.
- C3 deposition is an important prognostic marker in ANCA-GN.
Introduction:
Recent studies have revealed the pivotal role of complement activation in the pathogenesis of antineutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN). This study investigated the clinicopathologic and prognostic significance of glomerular C3 deposition in the renal histopathology of patients with ANCA-GN.
Methods:
We retrospectively identified 142 patients with ANCA-GN from 6 hospitals in Japan (2004-2020). C3 deposition was defined as C3 staining ≥1+ on a scale of 0 to 2+ using direct immunofluorescence (IF). The primary composite end points included a 30% reduction in estimated glomerular filtration rate (eGFR), end-stage kidney disease (ESKD), and death. We compared clinicopathologic features and long-term outcomes between patients with and without C3 deposition.
Results:
C3 deposition was observed in 56 of 142 kidney biopsy samples (39.4%). Patients with C3 deposition had a lower serum C3 level (P = 0.002). During a median follow-up of 2.9 (interquartile range: 0.2-5.7) years, 69 events occurred and the cumulative event-free survival rate at 5 years was significantly lower in the C3-positive group than in the C3-negative group (log-rank: P = 0.002). In multivariable analysis, C3 deposition was significantly associated with the composite end points after adjusting for age, sex, baseline eGFR, serum C3 level, treatment, and the percentage of normal glomerulus, cellular crescents, global sclerosis, and interstitial damage (adjusted hazard ratio [HR] = 2.02, 95% confidence interval: 1.20-3.40, P = 0.008).
Conclusion:
This study revealed that ANCA-GN patients with glomerular C3 deposition on IF had worse renal and overall survival rates.
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