Serum ferritin is a superior biomarker for evaluating disease activity and kidney injury compared with C-reactive protein in anti-neutrophil cytoplasmic antibody-associated vasculitis.

Background: Elevated C-reactive protein (CRP) is a characteristic of active anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, its relationship with organ involvement severity is ambiguous. Serum ferritin (SF) is a proinflammatory marker elevated in many autoimmune diseases, yet its role in AAV is poorly studied.

Methods: A total of 399 AAV patients were retrospectively selected and divided into four groups based on SF and CRP levels. Clinical, laboratory, and pathological data were compared. Survival analyses were conducted to estimate end-stage renal disease (ESRD) and death.

Results: In this cohort, 256 patients (64.16%) had elevated SF, and 289 (72.43%) had elevated CRP. Patients with elevated SF and normal CRP had the highest BVAS, lowest initial estimated glomerular filtration rate, highest 24-h proteinuria, and worst renal prognosis. SF showed a weak positive correlation with BVAS (R = 0.201, p < 0.001), while CRP showed a weak negative correlation with proteinuria (R = - 0.158, p = 0.002). Univariate Cox regression analysis revealed high SF level was a risk factor for ESRD and death, whereas CRP was not. Pathological tests showed that patients with elevated SF had a higher proportion of glomeruli with cellular crescents compared to those with normal SF. CRP positively correlated serum complement 3 (C3) with SF as a control variable (R = 0.434, p < 0.001), while SF negatively correlated with C3 with CRP as a control variable (R = - 0.201, p < 0.001).

Conclusion: In active AAV, high SF is associated with severe injury and poor kidney prognosis, whereas CRP is not. The underlying mechanism may be related to the different impacts on the complement system. Key Points • Patients with elevated SF and normal CRP had the highest BVAS, lowest initial estimated glomerular filtration rate, highest 24-hour proteinuria, and worst renal prognosis. . • CRP positively correlated serum C3 with SF as a control variable, while SF negatively correlated with C3 with CRP as a control variable. • High SF reflects a high proportion of glomeruli with cellular crescents in renal histopathology.