Hjelmesaeth Jøran, Ueland Thor, Flyvbjerg Allan, Bollerslev Jens, Leivestad Torbjørn, Jenssen Trond, Hansen Troels Krarup, Thiel Steffen, Sagedal Solbjørg, Røislien Jo, Hartmann Anders
Department of Medicine, Rikshospitalet University Hospital, University of Oslo, Norway.
J Am Soc Nephrol. 2006 Jun;17(6):1746-54. doi: 10.1681/ASN.2005121368. Epub 2006 May 10.
The primary objectives of this analysis were to examine the effects of early posttransplantation (10 wk) serum levels of osteoprotegerin (OPG), mannose-binding lectin (MBL), and MBL-associated serine proteases (MASP; MASP-2 and MASP-3) on long-term (8-yr) patient survival, graft survival, and cardiovascular (CV) death. During a period of 16 mo (1995 to 1996), a total of 173 consecutive renal transplant recipients without diabetes before transplantation were included in a prospective study that was designed to address the impact of metabolic CV risk factors on survival and CV end points. Baseline sera from 172 patients were available for analysis. Follow-up data until January 1, 2004, were obtained from a national renal registry. Patients with high (fourth quartile) serum levels of OPG had significantly higher all-cause mortality (hazard ratio [HR] 6.3; 95% confidence interval [CI] 3.3 to 11.8; P<0.001) and CV death (HR 10.8; 95% CI 3.8 to 30.4; P<0.001) than patients with lower OPG concentrations. After multiple Cox regression analysis, high serum levels of OPG remained an independent predictor of all-cause mortality (HR 6.0; 95% CI 3.1 to 11.6, P<0.001) and CV death (HR 8.2; 95% CI 2.5 to 26.4; P<0.001). Multiple linear regression analysis revealed that age, creatinine clearance, and high-sensitivity C-reactive protein all were independently associated with OPG (R2=0.42). No significant association between OPG and death-censored graft loss was revealed. Serum levels of MBL, MASP-2, and MASP-3 were not significantly associated with patient survival, CV death, or graft loss. Early measured posttransplantation serum OPG is a highly significant independent predictor of death from any cause or CV death in white renal transplant recipients.
本分析的主要目的是研究移植后早期(10周)血清骨保护素(OPG)、甘露糖结合凝集素(MBL)和MBL相关丝氨酸蛋白酶(MASP;MASP-2和MASP-3)水平对患者长期(8年)生存率、移植物生存率和心血管(CV)死亡的影响。在1995年至1996年的16个月期间,共有173例移植前无糖尿病的连续肾移植受者纳入一项前瞻性研究,该研究旨在探讨代谢性CV危险因素对生存率和CV终点的影响。172例患者的基线血清可用于分析。直至2004年1月1日的随访数据来自国家肾脏登记处。血清OPG水平处于高值(第四四分位数)的患者全因死亡率(风险比[HR]6.3;95%置信区间[CI]3.3至11.8;P<0.001)和CV死亡率(HR 10.8;CI 3.8至30.4;P<0.001)显著高于OPG浓度较低的患者。经过多重Cox回归分析,血清OPG水平高仍然是全因死亡率(HR 6.0;95%CI 3.1至11.6,P<0.001)和CV死亡率(HR 8.2;95%CI 2.5至26.4;P<0.001)的独立预测因素。多重线性回归分析显示,年龄、肌酐清除率和高敏C反应蛋白均与OPG独立相关(R2=0.42)。未发现OPG与死亡审查的移植物丢失之间存在显著关联。MBL、MASP-2和MASP-3的血清水平与患者生存率、CV死亡或移植物丢失均无显著关联。移植后早期测定的血清OPG是白人肾移植受者任何原因死亡或CV死亡的高度显著独立预测因素。