Abstract

Vitamin D deficiency, cardiovascular disease and abnormal bone mineral metabolism are common in chronic kidney disease (CKD). Abnormal bone mineral metabolism has been linked to vascular calcification in CKD. Sclerostin has emerged as an important messenger in cross talk between bone-vascular axis. We analyzed sclerostin in subjects who participated in the randomized, double blind, placebo controlled trial investigating the effect of cholecalciferol supplementation on vascular function in non-diabetic CKD stage G3-4 and vitamin D ≤20ng/ml [CTRI/2013/05/003648]. Patients were randomized (1:1) to receive either two directly observed oral doses of 300,000 IU of cholecalciferol or matching placebo at baseline and 8 weeks. Of the 120 subjects enrolled, 58 in the cholecalciferol group and 59 in the placebo group completed the study. At baseline, serum levels of sclerostin were similar in both groups (cholecalciferol - median;190pg/ml, IQR;140-260pg/ml and placebo - median;180pg/ml, IQR; 140-240pg/ml, p=0.67). 16 weeks after cholecalciferol supplementation, there was no change in level of sclerostin (mean change;1.10 pg/ml, 95%CI; -27.34 to 29.34 pg/ml, p=0.25). However, a significant decrease in sclerostin level was noted in the placebo group (mean change; -31.94pg/ml, 95%CI; -54.76 to -9.13 pg/ml, p=0.002). Change (Δ) in sclerostin level at 16 weeks correlated negatively with Δ eGFR (r=-0.20, p=0.03) and positively with Δuric acid (r=0.37, p<0.001) but not with Δ25(OH) D (r=0.06, p=0.54), Δ iPTH (r=-0.03, p=0.78) ΔFGF23 (r=-0.08, p=0.38) and Δ1,25 (OH)2 D (r=-0.04, p=0.65). In conclusion, high dose cholecalciferol supplementation did not change sclerostin levels in non-diabetic stage 3-4 CKD subjects.