Baseline patient characteristics
The demographic and clinical characteristics of the study cohort are shown in Table 1. A total of 140 subjects (age range, 25–81 years) were enrolled, including 60 patients with DM (44.3%). Of these patients, the causes of CKD were chronic glomerulonephritis (n = 41, 29.3%), hypertensive renal disease (n = 39, 27.9%), diabetic nephropathy (n = 33, 23.6%), chronic interstitial nephritis (n = 15, 10.7%), polycystic kidney disease (n = 3, 2.1%), autoimmune diseases (n = 2, 1.4%) and other diseases (n = 7, 5.0%). There were 58, 36 and 46 patients in CKD stages 3 (41.4%), 4 (25.7%) and 5 (32.9%), respectively.
The median eGFR was 24.9 mL/min/1.73m2, and the median serum sclerostin concentration was 46.76 pmol/L. Carotid atherosclerotic plaques were detected in 104 subjects (74.3%). Males had significantly higher serum sclerostin levels compared with females (57.26 vs. 43.05 pmol/L; median, p < 0.001). While patients with a history of smoking (59.08 vs. 45.93 pmol/L; median, p = 0.063) and hypertension (47.75 vs. 34.41 pmol/L; median, p = 0.056) tended to have higher sclerostin levels compared with those without. Sclerostin levels were comparable between patients with and without DM (47.28 vs. 45.75 pmol/L; median, p = 0.273).
Relationships between serum sclerostin and both renal function and bone and mineral metabolism markers
With the deterioration of renal function, levels of serum sclerostin gradually increased. Spearman correlation analysis showed that serum sclerostin was negatively correlated with eGFR (r = -0.214, P = 0.011), and the sclerostin level in patients with CKD stage 5 was significantly higher than that in patients with CKD stage 3 (42.53 vs. 52.64 ng/mL, median, p = 0.048), but the levels were comparable in patients with CKD stage 3 and 4 (42.53 vs. 44.11 ng/mL, p = 0.741) and in patients with CKD stage 4 and 5 (44.11 vs. 52.64 ng/mL, p = 0.115), as shown in Figure 1. Spearman correlation analysis showed that serum sclerostin was negatively correlated with calcium (r = -0.225, P = 0.007), but positively correlated with phosphorus (r = 0.185, P = 0.028). There were no significant correlations between serum sclerostin and iPTH, hs-CRP or alkaline phosphatase.
Differences between the characteristics of the high and low sclerostin groups
The subjects (n = 140) were divided into two groups according to the median sclerostin levels (46.76pmol/L, “high” and “low” groups), as in previous studies . The subjects in the high group showed a higher proportion of male patients (p = 0.042) and higher levels of serum phosphate (p = 0.002), and lower levels of eGFR (p = 0.020), serum total calcium (p = 0.007), hemoglobin (p = 0.008) and ALP (p = 0.034). (Table 1).
Comparisons between patients with and without atherosclerotic plaques
Subjects were divided into two groups according to whether they had carotid atherosclerotic plaques or not: a plaque group (n = 104) and a non-plaque group (n = 36). The plaque group had higher levels of serum sclerostin (P = 0.013), as shown in Figure 2. Moreover, the plaque group was significantly older (P < 0.001) and had a higher prevalence of hypertension (P = 0.007) and DM (P < 0.001), compared with the non-plaque group. (Table 2).
Factors related to carotid atherosclerotic plaques
Unconditional logistic regression analysis was used to analyze the related factors for carotid atherosclerotic plaques, and age, body mass index (BMI), DM, hypertension, eGFR and sclerostin (p < 0.05) were used as independent variables, and the presence of carotid atherosclerotic plaques was used as the dependent variable. This analysis showed that age, BMI, DM and sclerostin were independent factors that were significantly related to the presence of carotid plaques, with odds ratios (ORs) of 1.136 (1.082, 1.192), 1.170 (1.000, 1.369), 3.372 (1.020, 11.142) and 1.026 (1.003,1.051), respectively (Table 3).