Prognostic Implications of Serum C3 Levels in Primary Membranous Nephropathy: A Retrospective Cohort Analysis

Abstract

Background: The complement system plays a crucial role in the pathogenesis of membranous nephropathy (MN). Serum complement 3 (C3) levels may be a prognostic marker. This study investigates the prognostic significance of serum C3 levels in patients with primary MN. Methods: This study aims to evaluate the prognostic value of serum C3 levels in primary MN by analyzing their associations with demographic, clinical, and histopathological features, as well as treatment outcomes. We used data from the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) Working Group, a nationwide registry. Results: A total of 1,259 biopsy-proven primary MN patients were included. Serum C3 levels were low in 45 (3.6%) patients. Patients with low serum C3 levels demonstrated higher baseline serum creatinine (1.3 +/- 1.1mg/dL vs. 0.9 +/- 0.8mg/ dL, p=0.006) and proteinuria (9714 +/- 6329 mg/24h vs. 7052 +/- 4463mg/24h, p=0.002), and lower albumin levels (2.3 +/- 0.8g/dL vs. 2.7 +/- 0.8g/ dL, p=0.007) compared to those with normal serum C3. At one-year follow-up, both groups showed significant decreases in proteinuria and increases in albumin levels. In repeated-measures analyses, creatinine and proteinuria showed significant differences over time between the C3 groups; albumin did not (p: 0.029, 0.013, and 0.705, respectively). The remission rates were not different between C3 groups, 10 cases (62.5%) in the Low group, and 432 cases (76.1%) in the Normal group, p: 0.237. Relapse rates were notably higher in patients with low serum C3 levels compared to those with normal serum C3 (62.5% vs. 38.0%, p=0.049). Multivariate analysis showed that age (HR: 1.017, 95% CI: 1.002-1.032, p=0.025) and serum albumin levels (HR: 0.759, 95% CI: 0.568-1.015, p=0.063) were significant predictors of remission, while serum C3 levels were not. Conclusion: Low serum C3 levels in primary MN are associated with worse baseline clinical and histopathological parameters and higher relapse rates, but are not independently predictive of remission. Serum C3 may be a useful prognostic marker for relapse risk.