Serum IgA/C3 ratio: a useful marker of disease activity in patients with IgA nephropathy

Objective High serum IgA and low serum C3 levels resulting from lectin and alternative pathway activation might be related to IgA nephropathy (IgAN) progression and exacerbation. This study examined whether the serum IgA/C3 ratio can serve as an IgAN progression marker. Methods (1) This nationwide multicenter retrospective study in Japan included 718 patients with biopsy-confirmed IgAN. The patients whose serum creatinine levels at the time of renal biopsy had doubled were defined as having disease progression. (2) Furthermore, to investigate the pathological significance of a reduction in serum IgA/C3 ratio, we reviewed 63 patients whose serum IgA and C3 data at the end of the observation period were obtained. Results (1) A Kaplan–Meier analysis of the patients with IgAN revealed that the group with a high serum IgA/C3 (≥ 3.3) had a significantly worse renal outcome. In a multivariate analysis of eGFR ≥ 60 mL/min per 1.73m 2 at the time of biopsy, poor renal outcome was significantly predicted by a serum IgA/C3 ratio of ≥ 3.3. (2) A 15% reduction in the change of serum IgA/C3 ratio was associated with a significantly higher percentage of complete remission of proteinuria. Among the four groups divided by treatment, both the serum IgA/C3 ratio and proteinuria were reduced only in the tonsillectomy and steroid pulse group. Conclusion The serum IgA/C3 level might reflect the disease activity and be a potent surrogate marker of therapeutic efficacy in patients with IgAN.