Plasma osteoprotegerin is associated with mortality in hemodialysis patients.

Abstract

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.

• Authors: Marion Morena, Nathalie Terrier, Isabelle Jaussent, Hélène Leray-Moragues, Lotfi Chalabi, Jean-Pierre Rivory, François Maurice, Cécile Delcourt, Jean-Paul Cristol, Bernard Canaud, Anne-Marie Dupuy
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 17 Issue 1 Pg. 262-70 (Jan 2006) ISSN: 1046-6673 [Print] United States
• PMID: 16280472 (Publication Type: Journal Article)

Chemical References

• Carrier Proteins
• Glycoproteins
• Membrane Glycoproteins
• Osteoprotegerin
• Parathyroid Hormone
• RANK Ligand
• Receptor Activator of Nuclear Factor-kappa B
• Receptors, Cytoplasmic and Nuclear
• Receptors, Tumor Necrosis Factor
• TNFRSF11A protein, human
• TNFRSF11B protein, human
• TNFSF11 protein, human
• C-Reactive Protein

Topics

• Adult
• Aged
• Aged, 80 and over
• C-Reactive Protein (analysis)
• Carrier Proteins (blood)
• Female
• Glycoproteins (blood)
• Humans
• Male
• Membrane Glycoproteins (blood)
• Middle Aged
• Multivariate Analysis
• Osteoprotegerin
• Parathyroid Hormone (blood)
• Prospective Studies
• RANK Ligand
• Receptor Activator of Nuclear Factor-kappa B
• Receptors, Cytoplasmic and Nuclear (blood)
• Receptors, Tumor Necrosis Factor (blood)
• Renal Dialysis (mortality)
• Risk Factors