title: 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.affiliation: Biochemistry Laboratory, Lapeyronie University Hospital, 371 Avenue du Doyen Gaston Giraud, 34295 Montpellier cedex 5, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Morena
authors.forename: Nathalie
authors.initials: N
authors.lastname: Terrier
authors.forename: Isabelle
authors.initials: I
authors.lastname: Jaussent
authors.forename: Hélène
authors.initials: H
authors.lastname: Leray-Moragues
authors.forename: Lotfi
authors.initials: L
authors.lastname: Chalabi
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Rivory
authors.forename: François
authors.initials: F
authors.lastname: Maurice
authors.forename: Cécile
authors.initials: C
authors.lastname: Delcourt
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Cristol
authors.forename: Bernard
authors.initials: B
authors.lastname: Canaud
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Dupuy
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002097:C-Reactive Protein / Q000032:analysis; D002352:Carrier Proteins / Q000097:blood; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D015999:Multivariate Analysis; D053244:Osteoprotegerin; D010281:Parathyroid Hormone / Q000097:blood; D011446:Prospective Studies; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood*; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood*; D006435:Renal Dialysis / Q000401:mortality*; D012307:Risk Factors
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D010281:Parathyroid Hormone; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D002097:C-Reactive Protein