제1저자 윤창윤(내과학교실), 박지민(내과학교실, BK21, 지도 강신욱 교수), 서창환(내과학교실)
J Bone Miner Res. 2016 Decᜫ(12):2149-2158. doi: 10.1002/jbmr.2907. Epub 2016 Sep 7.
Low Dentin Matrix Protein 1 Is Associated With Incident Cardiovascular Events in Peritoneal Dialysis Patients.
Yoon CY1, Park J2, Seo C1, Nam BY2, Kim S2, Kee YK1, Lee M1, Cha MU1, Kim H1, Park S1, Yun HR1, Jung SY1, Jhee JH1, Kwon YE1, Wu M2, Um JE2, Kang HY2, Park JT1, Han SH1, Kang SW1,2, Kim HC3,4, Park S5, Lim SK6, Yoo TH1.
1Division of Nephrology, Department of Internal Medicine, Institute of Kidney Disease Research, Yonsei University College of Medicine, Seoul, Republic of Korea.2Department of Internal Medicine, College of Medicine, Severance Biomedical Science Institute, Brain Korea 21 PLUS, Yonsei University, Seoul, Republic of Korea.3Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.4Cardiovascular and Metabolic Disease Etiology Research Center, Yonsei University College of Medicine, Seoul, Republic of Korea.5Division of Cardiology, Cardiovascular Hospital, Yonsei University Health System, Seoul, Republic of Korea.6Division of Endocrinology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
Recent reports demonstrated that dentin matrix protein 1 (DMP1) acts as an inhibitor of vascular calcification and might be a potential biomarker for chronic kidney disease-mineral and bone disorder; however, no clinical investigations regarding DMP1 have been performed in dialysis patients. We investigated the prognostic value of DMP1 on cardiovascular outcomes in prevalent peritoneal dialysis patients. We recruited 223 prevalent peritoneal dialysis patients and divided them into high and low DMP1 groups according to log-transformed plasma DMP1 levels. Lateral lumbar spine radiographs were used for measurement of vascular calcification. Major cardiovascular events were compared between the two groups. A Cox proportional hazards analysis determined DMP1 was independently associated with cardiovascular outcomes. In vitro mouse osteocytes were cultured in media containing indoxyl sulfate (IS), and the expressions of DMP1 were examined. The mean age was 52.1 ;± .8 years, and 116 (52.0%) patients were male. The median value of log DMP1 was 0.91 (0.32-2.81 ;ng/mL). The multiple logistic regression analysis indicated that DMP1 levels were independently associated with the presence of vascular calcification after adjustment for multiple confounding factors (odds ratio ;= Ɏ.719; 95% confidence interval [CI] 0.522-0.989; p ;= Ɏ.043). During a mean follow-up duration of 34.6 months, incident cardiovascular events were observed in 41 (18.4%) patients. A Kaplan-Meier plot showed that the low DMP1 group had a significantly higher rate of incident cardiovascular events compared with the high DMP1 group (log-rank test, p ;= Ɏ.026). In addition, multiple Cox analysis showed that low DMP1 was significantly associated with incident cardiovascular events (log 1 increase: hazard ratio ;= Ɏ.855; 95% CI 0.743-0.984; p ;= Ɏ.029) after adjustment for multiple confounding factors. In IS-stimulated osteocytes, mRNA and protein expression levels of DMP1 were significantly decreased compared with control osteocytes. We showed that low DMP1 levels were significantly associated with presence of vascular calcification and were independently associated with the incident cardiovascular events in prevalent peritoneal dialysis patients. DMP1 might be a potential factor contributing to cardiovascular complications in dialysis patients.