Mesangial C4d Deposition is Independently Associated with Poor Renal Survival in Patients with Primary Focal Segmental Glomerulosclerosis

Background: C4d deposition is defined as the footprint of immune injury and it is associated with unfavorable renal outcomes in patients with IgA nephropathy. We searched whether mesangial C4d deposition is associated with poor renal survival in patients with primary focal segmental glomerulosclerosis (FSGS).

Methods: Biopsy specimens were stained with anti-C4d antibody. Patients were classified based on mesangial C4d deposition as C4d-negative and C4d-positive. Groups were compared according to baseline and follow-up clinical variables. Factors that predict renal progression and treatment failure were determined using Cox-regression and multivariate logistic regression models, respectively.

Results: Forty-one FSGS patients were followed for a mean of 67.7 ± 40.8 months. C4d-positive group included 18 patients while remaining 23 patients were C4d-negative. Urinary protein excretion and serum creatinine levels at baseline were comparable between groups. Fifteen patients reached the composite primary endpoint which included serum creatinine increasing > 30% from the baseline and reaching > 1.5 mg/dl, and/or evolution to end-stage renal disease (36.6%). In multivariate regression analysis, baseline eGFR (OR 0.71, 95% CI 0.53-0.94; p = 0.016) and mesangial C4d deposition (OR 10.5, 95% CI 1.51-73.18; p = 0.018) were independently associated with treatment failure rates. Mesangial C4d deposition was independently associated with the progression to the primary endpoint (HR 6.54, 95% CI 1.49-28.7, p = 0.013).

Conclusion: We showed for the first time that mesangial C4d deposition is an independent predictor of disease progression and treatment failure in patients with primary FSGS.