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Serum C3 and Renal Outcome in Patients with Primary Focal Segmental Glomerulosclerosis
Jian Liu1,2, Jingyuan Xie3,4, Xiaoyan Zhang1,2
1Institute of Nephrology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Insights
Low serum complement C3 levels in focal segmental glomerulosclerosis (FSGS) patients indicate a higher risk of kidney disease progression. This finding highlights complement C3 as a crucial biomarker for predicting FSGS outcomes.
Area of Science:
- Nephrology
- Immunology
- Pathophysiology
Background:
- The role of complement (C) in focal segmental glomerulosclerosis (FSGS) pathogenesis remains unclear.
- Understanding complement's involvement is crucial for identifying disease progression markers.
Purpose of the Study:
- To assess the relationship between serum C3 levels and FSGS progression.
- To identify clinical implications of serum C3 levels in FSGS patients.
Main Methods:
- Retrospective analysis of FSGS patient cohorts.
- Comparison of baseline characteristics and clinical outcomes based on serum C3 levels (≥85 mg/dL vs. <85 mg/dL).
- Correlation analysis of complement components (MAC, AP) with C3 and tubulointerstitial injury (TI).
Main Results:
- Patients with low serum C3 (<85 mg/dL) showed worse baseline characteristics, including higher creatinine and severe tubulointerstitial injury.
- Low serum C3 was a significant independent risk factor for end-stage renal disease (ESRD) development (p<0.001).
- Complement activation markers (MAC, AP) correlated with serum C3 and disease severity, with higher MAC and lower C3/AP in severe TI.
Conclusions:
- Complement activation in FSGS is linked to clinical and histological severity.
- Low serum C3 is an independent predictor of poor renal outcomes in FSGS patients.
Abstract:
The role of complement (C) in the pathogenesis or progression of focal segmental glomerulosclerosis (FSGS) is uncertain. The present study assessed the relationship between serum C3, the baseline characteristics, and the progression of FSGS in the cohort and identified the clinical implications of serum C3 levels in patients with FSGS. Compared to the patients with C3 ≥ 85 mg/dL (N = 474), those with C3 < 85 mg/dL (N = 117) presented a higher level of serum creatinine, lower levels of eGFR, hemoglobin, proteinuria, triglyceride, cholesterol, IgA, as well as, severe tubulointerstitial injury (TI). Of the 221 patients with a mean follow-up of 53.3 months, the risk of reaching end-stage renal disease (ESRD) was significantly higher in patients with low serum C3 level (p < 0.001). An additional 40 patients with primary FSGS revealed a significant correlation between MAC and AP (p = 0.003), MAC and serum C3 (p = 0.018), and AP and serum C3 (p = 0.028). Compared to patients with none-to-mild TI, those with moderate-to-severe TI exhibited a lower level of serum C3 and AP, and a higher level of serum MAC. In conclusion, complement activation occurring in patients with FSGS is associated with clinical and histological severities. Low serum C3 was an independent risk factor for poor renal outcome in patients with FSGS.
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