Elevated Osteoprotegerin Levels Predict Cardiovascular Events in New Hemodialysis Patients

Background: Patients on hemodialysis (HD) frequently experience cardiovascular events associated with vascular calcification. We investigated the involvement of osteoprotegerin (OPG), an inhibitor of vascular calcification, in the incidence of cardiovascular events and mortality among new HD patients. Methods: We conducted a prospective cohort study of the association of serum OPG levels with morbidity and mortality in subjects who became new HD patients between June 2000 and May 2006. Results: A total of 99 patients (age 58.9 ± 14.6 years, 65 male, 34 female) were prospectively followed up for 41.5 ± 20.2 months. During this period, 27 patients developed cardiovascular events and 12 died of causes related to cardiovascular disease. When divided into 2 groups according to OPG levels, the high OPG group showed a higher prevalence of cardiovascular morbidity and mortality compared with the low OPG group. Cox’s proportional hazards analysis associated the new onset of cardiovascular events with the high OPG group (HR 2.88, 95% CI 1.09–7.62, p = 0.033). Furthermore, the high OPG group at the start of HD was significantly associated with older age, male gender and a high aortic calcification index. Conclusions: Elevated levels of serum OPG in new HD patients may predict subsequent cardiovascular events.

[1]  S. Khalifé,et al.  Osteoprotegerin in relation to body weight, lipid parameters insulin sensitivity, adipocytokines, and C-reactive protein in obese and non-obese young individuals: results from both cross-sectional and interventional study. , 2008, European journal of endocrinology.

[2]  D. Brancaccio,et al.  Vascular Calcification and Uremia: What Do We Know? , 2007, American Journal of Nephrology.

[3]  K. Polkinghorne,et al.  Associations between vascular calcification, arterial stiffness and bone mineral density in chronic kidney disease. , 2007, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[4]  T. Eto,et al.  Risk factors of the progression of abdominal aortic calcification in patients on chronic haemodialysis. , 2007, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[5]  M. Inaba,et al.  Presence of abdominal aortic calcification is significantly associated with all-cause and cardiovascular mortality in maintenance hemodialysis patients. , 2007, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[6]  A. Lahiri,et al.  The relationship between plasma osteoprotegerin levels and coronary artery calcification in uncomplicated type 2 diabetic subjects. , 2006, Journal of the American College of Cardiology.

[7]  R. Mehrotra Disordered mineral metabolism and vascular calcification in nondialyzed chronic kidney disease patients. , 2006, Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation.

[8]  I. Jaussent,et al.  Plasma osteoprotegerin is associated with mortality in hemodialysis patients. , 2005, Journal of the American Society of Nephrology : JASN.

[9]  D. Brancaccio,et al.  Pathogenesis of vascular calcification in chronic kidney disease. , 2005, Kidney international.

[10]  N. Chen,et al.  Role of calcification inhibitors in the pathogenesis of vascular calcification in chronic kidney disease (CKD). , 2005, Kidney international.

[11]  F. Port,et al.  Predictors and consequences of altered mineral metabolism: the Dialysis Outcomes and Practice Patterns Study. , 2005, Kidney international.

[12]  P. Collin‐Osdoby Regulation of Vascular Calcification by Osteoclast Regulatory Factors RANKL and Osteoprotegerin , 2004, Circulation research.

[13]  K. Preissner,et al.  Localization of osteoprotegerin, tumor necrosis factor-related apoptosis-inducing ligand, and receptor activator of nuclear factor-kappaB ligand in Mönckeberg's sclerosis and atherosclerosis. , 2004, The Journal of clinical endocrinology and metabolism.

[14]  P. Raggi,et al.  Coronary and aortic calcifications in patients new to dialysis , 2004, Hemodialysis international. International Symposium on Home Hemodialysis.

[15]  G. London,et al.  Arterial calcifications and bone histomorphometry in end-stage renal disease. , 2004, Journal of the American Society of Nephrology : JASN.

[16]  K. Nitta,et al.  Serum osteoprotegerin levels and the extent of vascular calcification in haemodialysis patients. , 2004, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[17]  W. Poewe,et al.  Osteoprotegerin Is a Risk Factor for Progressive Atherosclerosis and Cardiovascular Disease , 2004, Circulation.

[18]  Bertram L Kasiske,et al.  Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. , 2003, Hypertension.

[19]  G. London,et al.  Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. , 2003, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[20]  K. Nitta,et al.  The progression of vascular calcification and serum osteoprotegerin levels in patients on long-term hemodialysis. , 2003, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[21]  P. Poulsen,et al.  Increased plasma concentrations of osteoprotegerin in type 2 diabetic patients with microvascular complications. , 2003, European journal of endocrinology.

[22]  N. Fineberg,et al.  Assessment of vascular calcification in ESRD patients using spiral CT. , 2003, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[23]  Y. Ikari,et al.  Serum Osteoprotegerin Levels Are Associated With the Presence and Severity of Coronary Artery Disease , 2002, Circulation.

[24]  M. Bahner,et al.  Advanced Coronary and Carotid Arteriopathy in Young Adults With Childhood-Onset Chronic Renal Failure , 2002, Circulation.

[25]  P. Raggi,et al.  Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. , 2002, Kidney international.

[26]  R. Oberbauer,et al.  Osteoprotegerin and parathyroid hormone as markers of high-turnover osteodystrophy and decreased bone mineralization in hemodialysis patients. , 2002, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[27]  T. Shigematsu,et al.  Increased circulating levels of osteoclastogenesis inhibitory factor (osteoprotegerin) in patients with chronic renal failure. , 2002, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[28]  E. Bonucci,et al.  Serum osteoprotegerin and renal osteodystrophy. , 2002, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[29]  S. Ganesh,et al.  Association of elevated serum PO(4), Ca x PO(4) product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients. , 2001, Journal of the American Society of Nephrology : JASN.

[30]  J. Blacher,et al.  Arterial Calcifications, Arterial Stiffness, and Cardiovascular Risk in End-Stage Renal Disease , 2001, Hypertension.

[31]  L. Adrienne Cupples,et al.  Abdominal Aortic Calcific Deposits Are an Important Predictor of Vascular Morbidity and Mortality , 2001, Circulation.

[32]  S. Cummings,et al.  Associations of serum osteoprotegerin levels with diabetes, stroke, bone density, fractures, and mortality in elderly women. , 2001, The Journal of clinical endocrinology and metabolism.

[33]  R. Elashoff,et al.  Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. , 2000, The New England journal of medicine.

[34]  R. Foley,et al.  Clinical epidemiology of cardiovascular disease in chronic renal disease. , 1998, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[35]  S. Morony,et al.  osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. , 1998, Genes & development.

[36]  F. Port,et al.  Association of serum phosphorus and calcium x phosphate product with mortality risk in chronic hemodialysis patients: a national study. , 1998, American journal of kidney diseases : the official journal of the National Kidney Foundation.