Serum IgA/C3 ratio as a diagnostic and prognostic biomarker for IgA nephropathy

IgA nephropathy (IgAN) is a common glomerular disease in adults with a smoldering course and high risk of progression to end-stage kidney disease (ESKD) in South Asians. We investigated serum IgA/C3 ratio as a potential biomarker for IgAN. We measured serum levels of IgA and C3 in 258 patients with IgAN and 90 controls with non-IgAN primary glomerular disease and examined if serum IgA/C3 ratio differentiates IgAN from other glomerular diseases and if it predicts renal survival in IgAN. The primary outcome was lack of renal survival, defined as irreversible decline in eGFR > 50% from baseline or progression to ESKD. Median serum IgA/C3 ratio was higher in IgAN patients compared to controls (2.4, IQR: 1.9-3.0 vs. 1.8, IQR: 1.3-2.5, p < 0.001). The AUC for the receiver operating curve of IgA/C3 ratio was 0.6760 (95% CI: 0.6074-0.7446). The sensitivity and specificity of IgA/C3 ratio > 2.0 were 70.5% and 62.2% respectively, for differentiating IgAN from other non-IgAN glomerular diseases. With a median duration of follow-up of 35.0(IQR 16-56.8) months, 26.7% patients reached the primary outcome. Compared to patients with a low IgA/C3 ratio(≤ 2.0), those with a high ratio(> 2.0) were significantly older [median age 34 vs. 29 years, p = 0.003], more likely to have hypertension (70.6% vs. 50.5%, p = 0.001), had lower median eGFR [47.7 mL/min/1.73 m² vs. 77.7 mL/min/1.73 m², p < 0.001], lower urine protein creatinine ratio [2.0 g/g vs. 2.5 g/g, p = 0.015] and a significantly higher proportion of segmental glomerulosclerosis (S1 lesions) (80.4% vs. 62.1%, p = 0.005). Renal disease progression was comparable (26.3% vs. 27.0%, p = 0.906) between the low and high IgA/C3 ratio groups respectively. High IgA/C3 ratio (> 2.0) was not a significant predictor of primary outcome (HR = 1.32 95% CI: 0.80-2.2, p = 0.278). Serum IgA/C3 ratio is elevated in IgAN compared to other glomerular diseases but has limited diagnostic and prognostic utility in our patients.