Plasma osteoprotegerin is associated with mortality in hemodialysis patients

• Published in: Journal of the American Society of Nephrology Vol. 17; no. 1; pp. 262 - 270
• Main Authors: MORENA, Marion, TERRIER, Nathalie, DUPUY, Anne-Marie, JAUSSENT, Isabelle, LERAY-MORAGUES, Hélène, CHALABI, Lotfi, RIVORY, Jean-Pierre, MAURICE, Francois, DELCOURT, Cécile, CRISTOL, Jean-Paul, CANAUD, Bernard
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 2006; American Society of Nephrology
• Subjects: Adult; Aged; Aged, 80 and over; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biochemistry, Molecular Biology; Biological and medical sciences; C-Reactive Protein; C-Reactive Protein - analysis; Carrier Proteins; Carrier Proteins - blood; Emergency and intensive care: renal failure. Dialysis management; Endocrinology and metabolism; Female; Glycoproteins; Glycoproteins - blood; Human health and pathology; Humans; Intensive care medicine; Life Sciences; Male; Medical sciences; Membrane Glycoproteins; Membrane Glycoproteins - blood; Middle Aged; Multivariate Analysis; Nephrology. Urinary tract diseases; Osteoprotegerin; Parathyroid Hormone; Parathyroid Hormone - blood; Prospective Studies; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors; Receptors, Cytoplasmic and Nuclear; Receptors, Cytoplasmic and Nuclear - blood; Receptors, Tumor Necrosis Factor - blood; Renal Dialysis - mortality; Risk Factors; Santé publique et épidémiologie; Human; Extrarenal dialysis; Nephrology; Hemodialysis; Mortality; Urology; Blood plasma; Osteoprotegerin; hemodialysis; mortality; cardiovascular disease; markers of mineral metabolism; osteoprotegerin
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/ASN.2005030260

Expression of bone proteins resulting from transdifferentiation of vascular smooth muscle cells into osteoblasts suggests that vascular calcifications are a bioactive process. Regulating molecules such as osteoprotegerin (OPG) and receptor activator of NF-kappaB ligand (RANKL) could play a key role in bone-vascular calcification imbalance. This study investigated the contribution of these proteins as well as mineral metabolism disorders in hemodialysis (HD) patient outcome. A total of 185 HD patients were followed up prospectively for 2 yr. In addition to clinical characteristics, mineral metabolism markers as well as OPG and soluble RANKL (sRANKL) were measured at baseline. After 2 yr, survival rates were described with Kaplan-Meier and compared with Cox regression analyses; 50 patients died (27 from cardiovascular diseases). Calcium, phosphate, and calcium x phosphate product were not associated with mortality. Both hyperparathyroidism (parathyroid hormone > or =300 pg/ml) and hypoparathyroidism (parathyroid hormone <150 pg/ml) were poorly associated with all-cause and cardiovascular mortality. By contrast, elevated OPG levels predicted all-cause (relative risk [RR] 2.67; 95% confidence interval [CI] 1.32 to 5.41; P = 0.006) and cardiovascular mortality (RR 3.15; 95% CI 1.14 to 8.69; P = 0.03). Low levels of sRANKL were associated with a protective effect for all-cause mortality (RR 0.45; 95% CI 0.21 to 0.94; P = 0.03). The association of OPG with all-cause mortality was stronger in patients with C-reactive protein > or =12.52 mg/L. In this condition, both highest (RR 5.68; 95% CI 1.48 to 22.73; P = 0.01) and lowest tertiles (RR 5.37; 95% CI 147 to 1968; P = 0.01) significantly predicted poor outcome. These results show that regulating-bone molecules, especially OPG, are strong predictors of mortality in HD patients, suggesting that OPG is a vascular risk factor, in particular in patients who have high C-reactive protein levels. OPG determination therefore should be added to the biologic follow-up of these patients.