Morena Marion, Terrier Nathalie, Jaussent Isabelle, Leray-Moragues Hélène, Chalabi Lotfi, Rivory Jean-Pierre, Maurice François, Delcourt Cécile, Cristol Jean-Paul, Canaud Bernard, Dupuy Anne-Marie
Biochemistry Laboratory, Lapeyronie University Hospital, 371 Avenue du Doyen Gaston Giraud, 34295 Montpellier cedex 5, France.
J Am Soc Nephrol. 2006 Jan;17(1):262-70. doi: 10.1681/ASN.2005030260. Epub 2005 Nov 9.
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.
血管平滑肌细胞转分化为成骨细胞所产生的骨蛋白表达表明，血管钙化是一个生物活性过程。骨保护素（OPG）和核因子κB受体活化因子配体（RANKL）等调节分子可能在骨 - 血管钙化失衡中起关键作用。本研究调查了这些蛋白以及矿物质代谢紊乱对血液透析（HD）患者预后的影响。共对185例HD患者进行了为期2年的前瞻性随访。除临床特征外，在基线时测量矿物质代谢标志物以及OPG和可溶性RANKL（sRANKL）。2年后，采用Kaplan - Meier法描述生存率，并通过Cox回归分析进行比较；50例患者死亡（27例死于心血管疾病）。钙、磷和钙磷乘积与死亡率无关。甲状旁腺功能亢进（甲状旁腺激素≥300 pg/ml）和甲状旁腺功能减退（甲状旁腺激素<150 pg/ml）与全因死亡率和心血管死亡率的相关性均较弱。相比之下，OPG水平升高可预测全因死亡率（相对风险[RR] 2.67；95%置信区间[CI] 1.32至5.41；P = 0.006）和心血管死亡率（RR 3.15；95% CI 1.14至8.69；P = 0.03）。低水平的sRANKL对全因死亡率具有保护作用（RR 0.45；95% CI
