Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
J Steroid Biochem Mol Biol. 2018 Jun;180:15-18. doi: 10.1016/j.jsbmb.2018.01.007. Epub 2018 Jan 10.
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 ≤ 20 ng/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;140-260 pg/ml and placebo - median;180 pg/ml, IQR; 140-240 pg/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; -31.94 pg/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 Δ125 (OH) 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.
维生素 D 缺乏、心血管疾病和异常的骨矿物质代谢在慢性肾脏病（CKD）中很常见。异常的骨矿物质代谢与 CKD 中的血管钙化有关。骨血管轴之间的串扰中，硬骨素已成为一种重要的信使。我们分析了参加随机、双盲、安慰剂对照试验的受试者的硬骨素，该试验研究了胆钙化醇补充剂对非糖尿病 CKD 3-4 期和维生素 D≤20ng/ml[CTRI/2013/05/003648]患者血管功能的影响。患者按 1:1 随机分为两组，分别在基线和 8 周时接受 2 次直接口服 30 万 IU 胆钙化醇或匹配的安慰剂。在 120 名入组的受试者中，58 名在胆钙化醇组，59 名在安慰剂组完成了研究。在基线时，两组的血清硬骨素水平相似（胆钙化醇组中位数为 190pg/ml，IQR 为 140-260pg/ml，安慰剂组中位数为 180pg/ml，IQR 为 140-240pg/ml，p=0.67）。胆钙化醇补充 16 周后，硬骨素水平无变化（平均变化为 1.10pg/ml，95%CI 为-27.34 至 29.34pg/ml，p=0.25）。然而，安慰剂组的硬骨素水平显著下降（平均变化为-31.94pg/ml，95%CI 为-54.76 至-9.13pg/ml，p=0.002）。16 周时硬骨素水平的变化（Δ）与 ΔeGFR 呈负相关（r=-0.20，p=0.03），与 Δ尿酸呈正相关（r=0.37，p<0.001），但与 Δ25（OH）D（r=0.06，p=0.54）、ΔiPTH（r=-0.03，p=0.78）、ΔFGF23（r=-0.08，p=0.38）和 Δ125（OH）D（r=-0.04，p=0.65）无关。结论：高剂量胆钙化醇补充剂并未改变非糖尿病 3-4 期 CKD 患者的硬骨素水平。
