title: Low Dentin Matrix Protein 1 Is Associated With Incident Cardiovascular Events in Peritoneal Dialysis Patients.
abstract: 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.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Institute of Kidney Disease Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Chang-Yun
authors.initials: CY
authors.lastname: Yoon
authors.affiliation: Department of Internal Medicine, College of Medicine, Severance Biomedical Science Institute, Brain Korea 21 PLUS, Yonsei University, Seoul, Republic of Korea.
authors.forename: Jimin
authors.initials: J
authors.lastname: Park
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Institute of Kidney Disease Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Changhwan
authors.initials: C
authors.lastname: Seo
authors.affiliation: Department of Internal Medicine, College of Medicine, Severance Biomedical Science Institute, Brain Korea 21 PLUS, Yonsei University, Seoul, Republic of Korea.
authors.forename: Bo Young
authors.initials: BY
authors.lastname: Nam
authors.affiliation: Department of Internal Medicine, College of Medicine, Severance Biomedical Science Institute, Brain Korea 21 PLUS, Yonsei University, Seoul, Republic of Korea.
authors.forename: Seonghun
authors.initials: S
authors.lastname: Kim
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Institute of Kidney Disease Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Youn Kyung
authors.initials: YK
authors.lastname: Kee
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Institute of Kidney Disease Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Misol
authors.initials: M
authors.lastname: Lee
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Institute of Kidney Disease Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Min-Uk
authors.initials: MU
authors.lastname: Cha
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Institute of Kidney Disease Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyoungnae
authors.initials: H
authors.lastname: Kim
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Institute of Kidney Disease Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Seohyun
authors.initials: S
authors.lastname: Park
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Institute of Kidney Disease Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hae-Ryong
authors.initials: HR
authors.lastname: Yun
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Institute of Kidney Disease Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Su-Young
authors.initials: SY
authors.lastname: Jung
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Institute of Kidney Disease Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jong Hyun
authors.initials: JH
authors.lastname: Jhee
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Institute of Kidney Disease Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Young Eun
authors.initials: YE
authors.lastname: Kwon
authors.affiliation: Department of Internal Medicine, College of Medicine, Severance Biomedical Science Institute, Brain Korea 21 PLUS, Yonsei University, Seoul, Republic of Korea.
authors.forename: Meiyan
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Internal Medicine, College of Medicine, Severance Biomedical Science Institute, Brain Korea 21 PLUS, Yonsei University, Seoul, Republic of Korea.
authors.forename: Jae Eun
authors.initials: JE
authors.lastname: Um
authors.affiliation: Department of Internal Medicine, College of Medicine, Severance Biomedical Science Institute, Brain Korea 21 PLUS, Yonsei University, Seoul, Republic of Korea.
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Kang
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Institute of Kidney Disease Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jung Tak
authors.initials: JT
authors.lastname: Park
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Institute of Kidney Disease Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Seung Hyeok
authors.initials: SH
authors.lastname: Han
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Institute of Kidney Disease Research, Yonsei University College of Medicine, Seoul, Republic of Korea.|Department of Internal Medicine, College of Medicine, Severance Biomedical Science Institute, Brain Korea 21 PLUS, Yonsei University, Seoul, Republic of Korea.
authors.forename: Shin-Wook
authors.initials: SW
authors.lastname: Kang
authors.affiliation: Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.|Cardiovascular and Metabolic Disease Etiology Research Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyeon Chang
authors.initials: HC
authors.lastname: Kim
authors.affiliation: Division of Cardiology, Cardiovascular Hospital, Yonsei University Health System, Seoul, Republic of Korea.
authors.forename: Sungha
authors.initials: S
authors.lastname: Park
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sung-Kil
authors.initials: SK
authors.lastname: Lim
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Institute of Kidney Disease Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Tae-Hyun
authors.initials: TH
authors.lastname: Yoo
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000209:etiology* / Q000235:genetics; D016022:Case-Control Studies; D002460:Cell Line; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D015994:Incidence; D007200:Indican / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D051379:Mice; D008875:Middle Aged; D010011:Osteocytes / Q000378:metabolism; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D061205:Vascular Calcification / Q000209:etiology
chemical_list: C513309:DMP1 protein, human; D016326:Extracellular Matrix Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D007200:Indican
keywords: BONE MATRIX MINERALIZATION; DIALYSIS; OSTEOCYTES; VASCULAR CALCIFICATION