Serum sclerostin as a potential novel biomarker for heart valve calcification in patients with chronic kidney disease.

OBJECTIVE: To explore the correlation between change in sclerostin level and heart valve calcification in patients with chronic kidney disease (CKD) in stages 3-5, as well as the possible underlying mechanism, which could provide a clinical reference for the diagnosis and treatment of cardiovascular disease (CVD).

PATIENTS AND METHODS: 110 patients were divided into a healthy control group and three groups of patients with CKD stages 3, 4, and 5 according to CKD staging guidelines. Scr, BUN, AKP, TC, TG, HDL, LDL, Ca, Pi, and CRP were measured, and calcium-phosphate product (Ca×Pi) calculated. ELISA was used to measure the sclerostin level, and the estimated glomerular filtration rate (eGFR) was calculated by MDRD. Heart valve calcification was measured by a physician in the Cardiac Department of our hospital. The correlations between sclerostin-level change and heart valve calcification, as well as each index in CKD patients in stages 3-5, were analyzed.

RESULTS: Compared with the healthy control group, the serum Ca in CKD stage-3, stage-4, and stage-5 groups (p < 0.05) was reduced, and PTH was increased (p < 0.05). Blood Pi and Ca×Pi in the stage-4 and stage-5 groups were increased (p < 0.05). The serum sclerostin level increased with renal hypofunction in stage-3 CKD patients, and was significantly increased compared with that of the control group, reaching the highest level in the terminal stage (p < 0.01). Pearson correlation analysis indicated that serum sclerostin was negatively correlated with eGFR (r = -0.91, p < 0.001) and blood Ca (r= -0.271, p < 0.001), and positively correlated with SCr (r = 0.608, p < 0.001), blood Pi level (r = 0.295, p < 0.001), PTH (r = 0.334, p < 0.001), and Ca×Pi (r = 0.275, p < 0.001). The rate of heart valve calcification in the CKD patients in stage 5 was relatively high (11/30, 36.67%), and significantly higher than that in healthy controls (1/20, 5%; p < 0.01). Logistic regression analysis of heart valve calcification indicated that sclerostin was a risk factor for heart valve calcification in CKD patients in stages 3-5.

CONCLUSIONS: The sclerostin level gradually increased with renal hypofunction in CKD patients in stages 3-5, and the increase in serum sclerostin level in the CKD patients occurred earlier than the change in Pi and Ca×Pi. The risk of heart valve calcification in stage-5 CKD patients was significantly increased. Sclerostin is an independent risk factor for heart valve calcification in CKD patients.