The role of azurocidin in patients with familial Mediterranean fever and AA amyloidosis and its association with cardiovascular risk factors

Familial Mediterranean fever (FMF) is characterized by sporadic, recurrent attacks of fever and serosal inflammation. AA amyloidosis (AAA) is a disorder characterized by the extracellular tissue deposition of serum amyloid A protein (SAA). Azurocidin is a neutrophil-derived granule protein. We aimed to investigate the significance of azurocidin in FMF and AAA and the correlation between azurocidin levels and carotid artery intima media thickness (CA–IMT) and cardiovascular plaque existence.

A sum of 52 FMF patients were enrolled in the study. FMF patients were composed of two groups. Group-1 included 30 patients with non-complicated FMF. Group-2 included 22 patients whom received renal transplantation due to FMF complicated with AAA and being followed up at stable state for at least one year. 24 healthy individuals who matched with FMF patients in terms of age and gender consisted the control group.

We found statistically significant difference between patient and control groups in terms of urea (38.52 ± 19.96 mg/dl vs 29.08 ± 5.83 mg/dl; p = 0.003), creatinine (1.11 ± 0.39 mg/dl vs 0.91 ± 0.16 mg/dl; p = 0.002), serum uric acid (6.2 ± 2 mg/dl vs 4.5 ± 0.9 mg/dl; p < 0.001), serum CRP (8.62 ± 9.5 mg/dl vs 3.91 ± 3.9 mg/dl; p = 0.004), ferritin (151.4 ± 317 ng/ml vs 33.3 ± 34 ng/ml; p = 0.014), white blood cell (WBC) levels (7.97 ± 2.3 × 10^3/µL vs 6.6 ± 1.7 × 10^3/µL; p = 0.018), serum azurocidin levels (137.16 ± 65.62 ng/ml vs 102.35 ± 51.61 ng/ml; p = 0.015) and mean CA–IMT (0.57 ± 0.15 mm vs 0.47 ± 0.07 mm; p = 0.001). Comparison of group 1 and group 2 revealed statistically significant differences in terms of urea (26 ± 8 mg/dl vs 54 ± 19 mg/dl; p < 0.001), creatinine (0.87 ± 0.1 mg/dl vs 1.44 ± 0.3 mg/dl; p < 0.001), estimated glomerular filtration rate (eGFR) (99 ± 21 ml/min/1.73m² vs 53 ± 16 ml/min/1.73m²; p < .001), uric acid (4.9 ± 1.3 mg/dl vs 7.6 ± 1.7 mg/dl; p < 0.001), ferritin (31.7 ± 27 ng/ml vs 292.8 ± 431 ng/ml; p = 0.010) and albumin (4.5 ± 0.3 g/dl vs 4.1 ± 0.3 g/dl; p = 0.001). There was no statistically significant difference between group 1 and group 2 in terms of mean CA–IMT (CA–IMT (M) (mm): 0.54 ± 0.14 vs 0.62 ± 0.17, p = 0.057). Serum azurocidin levels were not significantly different between group 1 and group 2 (121.73 ± 53.24 ng/ml vs 158.19 ± 75.77 ng/ml; p = 0.061). In multivariate linear regression analysis (variables: MBP, urea, creatinine, eGFR, ferritin, uric acid, CA–IMT) azurocidin was independently associated with urea (t:2.658; p = 0.010) and CA–IMT (t:2.464; p = 0.017).

Based on our findings, azurocidin seems to be a good inflammation marker in patients with FMF. Increase in azurocidin levels might be associated with development of amyloidosis. Also, serum azurocidin levels may be used as a predictor of both inflammatory state and cardiovascular risk, especially when used with other markers such as CA–IMT.