Characteristics of patients

In terms of variables at diagnosis, the median age of the 79 patients was 64.0 years, and 40.5% and 59.5% of the patients were men and women, respectively. Thirty-eight, 24, and 17 patients were diagnosed with MPA, GPA, or EGPA, respectively. MPO-ANCA (or P-ANCA) and PR3-ANCA (or C-ANCA) were positive in 44 (55.7%) and 12 (15.2%) patients, respectively. The median BVAS, FFS, SF-36 PCS and MCS, and VDI were 5.0. 0, 52.5, 54.9, and 3.0, respectively. Among the organ involvements, the most common were lung involvement with 50 cases (63.3%), ear/nose/throat involvement with 41 cases (51.9%), and kidney involvement with 38 cases (48.1%). Of the 79 patients, 17, 25, and 14 had type 2 diabetes mellitus, hypertension, and dyslipidaemia, respectively. The median ESR and CRP were 21.0 mm/h and 3.6 mg/L, and serum syndecan1 was measured at 52.2 ng/mL as a median value. In terms of variables during follow-up, of the 79 patients, six (7.6%) died and 18 (22.8%) experienced progression to ESKD for the median follow-up durations based on each poor outcome of 26.7, and 26.3 months, respectively.

Of the 79 patients, 78 received glucocorticoids, and the most commonly administered immunosuppressive drug was cyclophosphamide, followed by azathioprine (Table 1).

Table 1 Characteristics of patients with AAV at diagnosis and during follow-up (N = 79)

Serum syndecan1 levels for all patients with MPA, GPA, and EGPA are presented in the Supplementary Fig. 1. The range of syndecan1 levels was from 14.97 to 1504 ng/mL.

Correlation of variables with serum syndecan1 at diagnosis

Serum syndecan1 at diagnosis was significantly correlated with BVAS (r = 0.364), FFS (r = 0.400), all-cause mortality (r = 0.291), ESR (r = 0.505), CRP (r = 0.286), white blood cell count (r = 0.353), blood urea nitrogen (r = 0.467), and serum creatinine (r = 0.397). Meanwhile, serum syndecan1 at diagnosis was inversely correlated with SF-36 PCS (r = − 0.373), SF-36 MCS (r = − 0.330), haemoglobin (r = − 0.405), and serum albumin (r = − 0.451) at diagnosis (Table 2).

Table 2 Correlation analysis of continuous variables for serum syndecan1 levels at diagnosis in patients with AAV (N = 79)Relative risks of cut-off of serum syndecan1 for high activity of AAV at diagnosis

Receiver operating tertile of BVAS, ROC) curve analysis revealed that the area under the curve (AUC of serum syndecan1 at diagnosis for the highest tertile of BVAS at diagnosis was statistically significant (0.864, 95% confidence interval 0.775, 0.953). The optimal cut-off of serum syndecan1 at diagnosis was calculated as the maximised summation of the sensitivity (70.4%) and specificity (90.4%) and was set as 76.1 ng/mL. When the patients were divided into two groups according to this cut-off, the highest tertile of BVAS at diagnosis was identified more often in patients with serum syndecan1 ≥ 76.1 ng/mL at diagnosis than those without (79.2% vs. 14.5%, P < 0.001). Furthermore, patients with serum syndecan1 ≥ 76.1 ng/mL at diagnosis showed a significantly higher risk for the highest tertile of BVAS at diagnosis than those without (RR 22.325, 95% CI 6.474, 76.985) (Fig. 1A).

Fig. 1

Optimal cut-off and relative risks of serum syndecan1 for high BVAS. BVAS, Birmingham vasculitis activity score; CI, confidence interval; RR, relative risk

Next, as for the upper half of BVAS, the optimal cut-off of serum syndecan1 was determined as 60.0 ng/mL (sensitivity, 64.4%; specificity, 79.4%) using the ROC curve analysis (AUC 0.752, 95% CI 0.647, 0.858). When the patients were divided into two groups according to this cut-off, patients with serum syndecan1 ≥ 60.0 ng/mL at diagnosis exhibited the upper half of BVAS at diagnosis more frequently than those without (80.6% vs. 37.2%, P < 0.001). Additionally, those with serum syndecan1 ≥ 60.0 ng/mL at diagnosis also showed a significantly higher risk for the upper half of BVAS at diagnosis than those without (RR 6.991, 95% CI 2.493, 19.608) (Fig. 1B).

Relative risks of cut-off of serum syndecan1 at diagnosis for all-cause mortality during follow-up

On the other hand, among the two poor outcomes of AAV during follow-up, the ROC curve analysis unveiled that the AUC of serum syndecan1 at diagnosis for all-cause mortality during follow-up was significant (AUC 0.817, 95% CI 0.628, 1.000). When the optimal cutoff of serum syndecan1 at diagnosis for all-cause mortality during follow-up was set at 120.1 ng/mL, the sensitivity and specificity were 83.3% and 87.7%, respectively. When patients were divided into two groups according to this cut-off, all-cause mortality during follow-up was found more often in patients with serum syndecan1 ≥ 120.1 ng/mL at diagnosis than those without (35.7% vs. 1.5%, P < 0.001). Moreover, patients with serum syndecan1 ≥ 120.1 ng/mL at diagnosis had a significantly higher risk for death than those without (RR 35.556, 95% CI 3.719, 339.904) (Fig. 2).

Fig. 2

Optimal cut-off and relative risks of serum syndecan1 for all-cause mortality. CI: confidence interval; RR: relative risk

Cumulative survival rate

Patients with serum syndecan1 ≥ 120.1 ng/mL at diagnosis exhibited a significantly lower cumulative patient survival rate during follow-up than those with serum syndecan1 < 120.1 ng/mL at diagnosis (P < 0.001) (Fig. 3).

Fig. 3

Comparison of cumulative survival rates

Cox analyses

In the univariate Cox proportional analysis, the BVAS at diagnosis was not significantly associated with all-cause mortality during follow-up. Meanwhile, serum syndecans1 ≥ 120.1 ng/mL at diagnosis (HR 42.273), along with SF-36 PCS (HR 0.943), VDI (HR 1.591), dyslipidaemia (HR 11.068), white blood cell count (HR 1.130), haemoglobin (HR 0.604), and serum albumin (HR 0.152) at diagnosis were significantly associated with all-cause mortality during follow-up. However, in the multivariable Cox analysis of variables with statistical significance in the univariate analysis, none were independently associated with all-cause mortality during follow-up. Nevertheless, both dyslipidaemia (HR 9.928, 95% CI 1.000, 98.552, P = 0.005) and serum syndecans-1 ≥ 120.1 ng/mL (HR 59.822, 95% CI 0.611, 5,860.343, P = 0.080) at diagnosis exhibited the possibility of the independent association with all-cause mortality during follow-up in patients with AAV (Table 3).

Table 3 Cox hazards model analyses of variables at diagnosis for all-cause mortality during follow-up in AAV patients