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Low Dentin Matrix Protein 1 Is Associated With Incident Cardiovascular Events in Peritoneal Dialysis Patients

 Chang-Yun Yoon  ;  Jimin Park  ;  Changhwan Seo  ;  Bo Young Nam  ;  Seonghun Kim  ;  Youn Kyung Kee  ;  Misol Lee  ;  Min-Uk Cha  ;  Hyoungnae Kim  ;  Seohyun Park  ;  Hae-Ryong Yun  ;  Su-Young Jung  ;  Jong Hyun Jhee  ;  Young Eun Kwon  ;  Meiyan Wu  ;  Jae Eun Um  ;  Hye-Young Kang  ;  Jung Tak Park  ;  Seung Hyeok Han  ;  Shin-Wook Kang  ;  Hyeon Chang Kim  ;  Sungha Park  ;  Sung-Kil Lim  ;  Tae-Hyun Yoo 
 Journal of Bone and Mineral Research, Vol.31(12) : 2149-2158, 2016 
Journal Title
 Journal of Bone and Mineral Research 
Issue Date
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?±?11.8 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?=?0.719; 95% confidence interval [CI] 0.522-0.989; p?=?0.043). 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?=?0.026). In addition, multiple Cox analysis showed that low DMP1 was significantly associated with incident cardiovascular events (log 1 increase: hazard ratio?=?0.855; 95% CI 0.743-0.984; p?=?0.029) 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. ? 2016 American Society for Bone and Mineral Research.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Preventive Medicine and Public Health (예방의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
강신욱(Kang, Shin Wook) ORCID logo https://orcid.org/0000-0002-5677-4756
강혜영(Kang, Hye Young)
권영은(Kwon, Young Eun)
기연경(Kee, Youn Kyung)
김현창(Kim, Hyeon Chang) ORCID logo https://orcid.org/0000-0001-7867-1240
김형래(Kim, Hyoung Rae)
남보영(Nam, Bo Young)
박서현(Park, Seo Hyun)
박성하(Park, Sung Ha) ORCID logo https://orcid.org/0000-0001-5362-478X
박정탁(Park, Jung Tak) ORCID logo https://orcid.org/0000-0002-2325-8982
서창환(Seo, Changhwan)
유태현(Yoo, Tae Hyun) ORCID logo https://orcid.org/0000-0002-9183-4507
윤창연(Yoon, Chang Yun)
윤해룡(Yun, Hae Ryong) ORCID logo https://orcid.org/0000-0002-7038-0251
이미솔(Lee, Mi Sol)
임승길(Lim, Sung Kil)
정수영(Jung, Su Young)
지종현(Jhee, Jong Hyun)
차민욱(Cha, Min Uk)
한승혁(Han, Seung Hyeok) ORCID logo https://orcid.org/0000-0001-7923-5635
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