【摘要】目的探讨维持性血液透析(maintenance hemodialysis,MHD)患者血清牙本质基质蛋白1(dentin matrix protein 1,DMP1)与矿物质代谢及骨密度的关系。方法以2019 年7 月～2020 年7 月于青岛大学附属青岛市市立医院血液净化中心行MHD 治疗的95 名患者作为研究对象。收集研究对象的临床资料和实验室检查结果，ELISA 测定血清DMP1 水平，双能X 线吸收法检测MHD 患者股骨颈骨密度。采用Spearman 相关性分析、多元线性回归分析MHD 患者血清DMP1 水平的影响因素。二元Logistic 回归分析MHD 患者发生骨密度低下的影响因素。结果①MHD 患者的血清DMP1 水平低于健康人群，差异有统计学意义(Z=-3.218,P =0.001)。②Spearman 相关性分析显示DMP1 水平与年龄、透析龄呈负相关，与肾小球滤过率(eGFR)、甲状旁腺激素(PTH)、股骨颈骨密度T 值呈正相关(r 值分别为-0.226，-0.223，0.210，0.294，0.370；P 值分别为0.028，0.030，0.041，0.004，＜0.001)。多元线性回归分析显示，血清DMP1 水平的独立影响因素是PTH 和股骨颈骨密度T 值(β 值分别为0.211，0.399；P 值分别为0.032，0.001)。③二元Logistic 回归分析显示，在调整了年龄、透析龄、白蛋白、碱性磷酸酶和血钙等混杂因素后，血清高DMP1 水平是MHD 患者发生骨密度低下的独立保护因素(OR：0.913，95% CI：0.845～0.986,P=0.020)。结论MHD 患者的血清DMP1 水平较健康人群低，且与矿物质代谢及骨密度相关。
【Abstract】Objective To investigate the relationship between serum level of dentin matrix protein 1(DMP1) and the status of mineral metabolism and bone density in maintenance hemodialysis (MHD) patients. Methods A total of 95 MHD patients treated at the Blood Purification Center of Qingdao Municipal Hospital from July 2019 to July 2020 were recruited as the research objects. Their clinical data and laboratory test results were collected, serum DMP1 was determined by ELISA, and femoral neck bone mineral density was assayed by dual-energy X-ray absorptiometry. The influencing factors for serum DMP1 level were evaluated by Spearman correlation analysis and multivariate linear regression, and the influencing factors for low bone mineral density were assessed by binary logistic regression. Results ①Serum DMP1 level was lower in the MHD patients than in the healthy controls (Z=-3.218, P=0.001). ②Spearman correlation analysis showed that DMP1 level was negatively correlated with age and dialysis duration, and positively correlated with eGFR, PTH, and T-score of femoral neck bone mineral density (r=-0.226, -0.223, 0.210, 0.294 and 0.370, respectively; P=0.028, 0.030, 0.041, 0.004 and <0.001, respectively). Multivariate linear regression demonstrated that PTH and T-score of femoral neck bone mineral density were the independent influencing factors for serum
DMP1 level (β=0.211 and 0.399, respectively; P=0.032 and 0.001, respectively). ③Binary logistic regression found that higher serum DMP1 level was an independent protective factor for the lower bone mineral density in MHD patients (OR=0.913, 95% CI 0.845~0.986, P=0.020) after adjusting the confounding factors including age, dialysis age, albumin, alkaline phosphatase and serum calcium. Conclusions Serum DMP1 level in MHD patients is lower than that in healthy controls, and the lower serum level is related to the changes of mineral metabolism and bone density.
[1] 刘志红，李贵森. 中国慢性肾脏病矿物质和骨异常诊治指南[M]. 北京: 北京人民出版社, 2018.
[2] Lu Y, Yuan B, Qin C, et al. The biological function of DMP-1 in osteocyte maturation is mediated by its 57-kDa C-terminal fragment [J]. J Bone Miner Res, 2011, 26(2): 331-340.
[3] George A, Sabsay B, Simonian P a L, et al. Characterization of a novel dentin matrix acidic phosphoprotein. Implications for induction of biomineralization[J]. J Biol Chem, 1993, 268(17): 12624-12630.
[4] Fisher LW, Torchia DA, Fohr B, et al. Flexible structures of SIBLING proteins, bone sialoprotein, and osteopontin[J]. Biochem Biophysi Res Commun, 2001, 280(2): 460-465.
[5] Narayanan K, Ramachandran A, Hao J, et al. Dual functional roles of dentin matrix protein 1. Implications in biomineralization and gene transcription by activation of intracellular Ca2 store[J]. J Biol Chem, 2003, 278(19): 17500-17508.
[6] Ichikawa S, Gerard-O'riley RL, Acton D, et al. A Mutation in the Dmp1 Gene Alters Phosphate Responsiveness in Mice[J]. Endocrinology, 2017, 158(3): 470-476.
[7] Martin A, Liu S, David V, et al. Bone proteins PHEX and DMP1 regulate fibroblastic growth factor Fgf23 expression in osteocytes through a common pathway involving FGF receptor (FGFR) signaling[J]. FASEB J, 2011, 25(8): 2551-2562.
[8] Dussold C, Gerber C, White S, et al. DMP1 prevents osteocyte alterations, FGF23 elevation and left ventricular hypertrophy in mice with chronic kidney disease[J]. Bone Res, 2019, 7(12): 12.
[9] Narayanan K, Gajjeraman S, Ramachandran A, et al. Dentin matrix protein 1 regulates dentin sialophosphoprotein gene transcription during early odontoblast differentiation[J]. J Biol Chem, 2006, 281(28): 19064-19071.
[10] Feng J, Ward L, Liu S, et al. Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism [J]. Nat Genet, 2006, 38(11): 1310-1315.
[11] Kurpas A, Supe? K, Idzikowska K, et al. FGF23: A Review of Its Role in Mineral Metabolism and Renal and Cardiovascular Disease [J]. Dis Markers, 2021, 5(2021): 8821292.
[12] Tsuchiya K, Akihisa T. The Importance of Phosphate Control in Chronic Kidney Disease[J]. Nutrients, 2021, 13(5): 1670.
[13] Scialla JJ, Xie H, Rahman M, et al. Fibroblast growth factor-23 and cardiovascular events in CKD[J]. J Am Soc Nephrol, 2014, 25(2): 349-360.
[14] Martin A. Bone and heart health in chronic kidney disease: role of dentin matrix protein 1[J]. Curr Opin Nephrol Hypertens, 2019, 28(4): 297-303.
