【摘要】目的探讨血清骨硬化蛋白(Sclerostin)与维持性血液透析(maintenance hemodialysis，MHD)患者腹主动脉钙化之间的关系。方法选择首都医科大学附属北京潞河医院肾病中心150 名维持性血液透析为研究对象，收集患者的人口统计学资料及临床资料，包括有无糖尿病及残余尿量的统计，尿量＜200ml 则视为无残余肾功能(residual renal function，RRF)。同时用酶联免疫吸附法(ELISA)检测血清Sclerostin、骨特异碱性磷酸酶(bone specific alkaline phosphatase，BsAP)。通过腹部侧位X 线片检测腹主动脉钙化(calcification of abdominal aorta，AAC)。分析Sclerostin 水平与MHD 患者iPTH、BsAP、腹主动脉钙化的相关关系。结果①首都医科大学附属北京潞河医院MHD 患者腹主动脉钙化的发生率为74%，按照有无AAC 将患者分为钙化组和无钙化组，结果显示钙化组Sclerostin、Kt/V 明显低于无钙化组(t 值分别为6.694，2.298; P 值分别为＜0.001,0.023)，而年龄、透析龄、iPTH、血清碱性磷酸酶、BsAP 均高于无钙化组(t 值分别为-5.250，-4.356，-2.926，-3.877，-4.654；P 值分别为＜0.001，＜0.001，＜0.001，＜0.001，＜0.001)，两组间性别、血钙、血磷等指标无统计学差异(t 值分别为2.345，-0.262，0.096；P 值分别为0.126，0.794，0.923)。②Logistic 回归分析MHD 患者血管钙化的危险因素：年龄(OR=1.134，95% CI 1.059～1.224，P＜0.001)、透析龄(OR=1.006，95% CI1.006～1.075，P=0.019)、有无残肾(OR=0.150，95% CI 0.027～0.818，P=0.028)、有无糖尿病(OR= 8.199，95% CI1.316～51.073，P=0.024)、iPTH(OR=1.009，95% CI 1.001～1.017，P=0.035)、Kt/V(OR=0.030，95% CI0.001～0.652，P=0.026)、Sclerostin(OR=0.985，95% CI 0.976～0.994，P=0.002)、BsAP(OR=1.295，95%CI 1.037～1.618，P=0.023)均有统计学意义。结论MHD 患者血管钙化发生率高，高龄、透析龄长、糖尿病、高iPTH、高BsAP 均为MHD 患者血管钙化的危险因素，而有残余肾功能、Sclerostin、Kt/V 是MHD 患者血管钙化的保护因素。
【Abstract】Objective To investigate the relationship between serum sclerostin and the degree of abdominal aortic calcification in patients undergoing maintenance hemodialysis(MHD). Methods 150 MHD patients in our hospital's nephropathy center were selected as subjects, Collect patient demographic data and clinical data, Including diabetes and residual urine volume, urine volume <200ml is considered as no residual renal function (RRF), Serum Sclerostin and bone specific alkalinephosphatase(BsAP) levels from 150 cases of MHD patients were measured by ELISA. Abdominal aortic calcification (AAC) was detected by lateral radiographs of the abdomen and AAC scores were performed. Analysis of the relationship between Sclerostin level and iPTH, BsAP and a AAC in patients with MHD. Results 1. The incidence of abdominal aortic calcification in patients with MHD was 74%. The patients were divided into calcified group and non-calcified group according to the presence or absence of AAC. The results showed that the sclerostin, kt/v in the calcified group was significantly lower than that in the non- calcified group (t=6.694, P<0.001). Age（t=- 5.250，P<0.001）, dialysis age (t=-4.356，P<0.001), iPTH(t=-2.926，P<0.001), serum alkaline phosphatase (t=-3.877，P<0.001), BsAP (t=-4.654，P<0.001)were higher than those without calcification (P<0.05). There were no significant differences in gender (t=2.345，P=0.126), serum calcium (t=- 0.262，P=0.794) and phosphorus (t= 0.096，P=0.923) between the two groups (P＞ 0.05). 2. Logistic regression analysis of risk factors for vascular calcification in patients with MHD: Age (OR=1.134, 95% CI, 1.059～1.224, P<0.001), dialysis age (OR=1.006, 95% CI, 1.006- 1.075, P= 0.019), RRF(OR=0.150, 95%CI, 0.027～0.818, P=0.028), Diabetes (OR=8.199, 95% CI, 1.316～51.073, P=0.024), iPTH (OR= 1.009, 95% CI, 1.001～1.017,P=0.035) , Kt/V(OR=0.030, 95% CI, 0.001～0.652, P=0.026), Sclerostin (OR=0.985, 95% CI, 0.976～0.994, P=0.002), BsAP(OR=1.295, 95% CI) , 1.037～1.618, P=0.023) were statistically significant. Conclusion The incidence of vascular calcification were higher in MHD patients.Agedness,Long-dialysis, diabetes, higher iPTH, and higher BsAP are risk factors for vascular calcification in patients with MHD,but RRF, Sclerostin, and Kt/V are protective
factors for vascular calcification in patients with MHD.
[1]. Moe, S., et al., Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int, 2006. 69(11): p. 1945-53.
[2]. Thompson, B. and D.A. Towler, Arterial calcification and bone physiology: role of the bone-vascular axis. Nat Rev Endocrinol, 2012. 8(9): p. 529-43.
[3]. Roman-Garcia, P., et al., High phosphorus diet induces vascular calcification, a related decrease in bone mass and changes in the aortic gene expression. Bone, 2010. 46(1): p. 121-8.
[4]. Baron R and G. Rawadi, Targeting the Wnt/beta-catenin pathway to regulate bone formation in the adult skeleton. Endocrinology, 2007. 148(6): p. 2635-43.
[5]. Koos, R., et al., Sclerostin as a potential novel biomarker for aortic valve calcification: an in-vivo and ex-vivo study. J Heart Valve Dis, 2013. 22(3): p. 317-25.
[6]. Zhu, D., et al., The appearance and modulation of osteocyte marker expression during calcification of vascular smooth muscle cells. PLoS One, 2011. 6(5): p. e19595.
[7]. Shanahan, C.M., et al., Arterial calcification in chronic kidney disease: key roles for calcium and phosphate. Circ Res, 2011. 109(6): p. 697-711.
[8]. Neven, E., et al., Chondrocyte rather than osteoblast conversion of vascular cells underlies medial calcification in uremic rats. Arterioscler Thromb Vasc Biol, 2010. 30(9): p. 1741-50.
[9]. Rachner, T.D., et al., Novel therapies in osteoporosis: PTH-related peptide analogues and inhibitors of sclerostin. J Mol Endocrinol, 2018.
[10]. Novo-Rodriguez, C., et al., Circulating levels of sclerostin are associated with cardiovascular mortality. PLoS One, 2018. 13(6): p. e0199504.
[11]. Drechsler, C., et al., High levels of circulating sclerostin are associated with better cardiovascular survival in incident dialysis patients: results from the NECOSAD study. Nephrol Dial Transplant, 2015. 30(2): p. 288-93.
[12]. Viaene, L., et al., Sclerostin: another bone-related protein related to all-cause mortality in haemodialysis? Nephrol Dial Transplant, 2013. 28(12): p. 3024-30.
[13]. Morales-Santana, S., et al., Atherosclerotic disease in type 2 diabetes is associated with an increase in sclerostin levels. Diabetes Care, 2013. 36(6): p. 1667-74.
[14]. Balci, M., et al., Sclerostin as a new key player in arteriovenous fistula calcification. Herz, 2015. 40(2): p. 289-97.
[15]. Li, M., et al., Relationship between serum sclerostin, vascular sclerostin expression and vascular calcification assessed by different methods in ESRD patients eligible for renal transplantation: a cross-sectional study. Int Urol Nephrol, 2018.
[16]. Jean, G., et al., High Serum Sclerostin Levels Are Associated with a Better Outcome in Haemodialysis Patients. Nephron, 2016. 132(3): p. 181-90.
[17]. Claes, K.J., et al., Sclerostin: Another vascular calcification inhibitor? J Clin Endocrinol Metab, 2013. 98(8): p. 3221-8.
[18]. Brandenburg, V.M., et al., Relationship between sclerostin and cardiovascular calcification in hemodialysis patients: a cross-sectional study. BMC Nephrol, 2013. 14: p. 219.
[19]. Haas, M., et al., Osteoprotegerin and parathyroid hormone as markers of high-turnover osteodystrophy and decreased bone mineralization in hemodialysis patients. Am J Kidney Dis, 2002. 39(3): p. 580-6.
[20]. Lomashvili, K.A., et al., Upregulation of alkaline phosphatase and pyrophosphate hydrolysis: potential mechanism for uremic vascular calcification. Kidney Int, 2008. 73(9): p. 1024-30.
[21]. Towler, D.A., Inorganic pyrophosphate: a paracrine regulator of vascular calcification and smooth muscle phenotype. Arterioscler Thromb Vasc Biol, 2005. 25(4): p. 651-4.
[22]. Riser, B.L., et al., Daily peritoneal administration of sodium pyrophosphate in a dialysis solution prevents the development of vascular calcification in a mouse model of uraemia. Nephrol Dial Transplant, 2011. 26(10): p. 3349-57.
[23]. Power, J., et al., Sclerostin and the regulation of bone formation: Effects in hip osteoarthritis and femoral neck fracture. J Bone Miner Res, 2010. 25(8): p. 1867-76.
[24]. Devarajan-Ketha, H., et al., The sclerostin-bone protein interactome. Biochem Biophys Res Commun, 2012. 417(2): p. 830-5.
