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循环可溶性血管细胞黏附分子1:与腹膜透析患者残余肾功能、心脏肥大及预后的关系

Circulating soluble vascular cell adhesion molecule 1: relationships with residual renal function, cardiac hypertrophy, and outcome of peritoneal dialysis patients.

作者信息

Wang Angela Yee-Moon, Lam Christopher Wai-Kei, Wang Mei, Woo Jean, Chan Iris Hiu-Shuen, Lui Siu-Fai, Sanderson John E, Li Philip Kam-Tao

机构信息

Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong.

出版信息

Am J Kidney Dis. 2005 Apr;45(4):715-29. doi: 10.1053/j.ajkd.2004.12.012.

Abstract

BACKGROUND

Vascular cell adhesion molecule 1 (VCAM-1) is involved in leukocyte-endothelial cell interaction and has a pivotal role in inflammation. Whether it contributes to excessive mortality in dialysis patients remains uncertain. In this study, we examined circulating soluble VCAM-1 (sVCAM-1) in relation to different clinical and biochemical parameters, as well as mortality and cardiovascular events, in peritoneal dialysis (PD) patients.

METHODS

Values for serum sVCAM-1, together with C-reactive protein (CRP), homocysteine, albumin, lipid profile, blood hemoglobin, and indices of dialysis adequacy, were determined at study baseline, and echocardiography was performed in 160 long-term PD patients. Patients were followed up for a mean of 35 +/- 16 (SD) months.

RESULTS

Serum sVCAM-1 levels were elevated in our continuous ambulatory PD (CAPD) patients and showed a negative correlation with residual glomerular filtration rate (GFR; P < 0.001) and low-density lipoprotein (LDL) cholesterol level (P = 0.004), but a positive correlation with left ventricular mass index (P = 0.025). Using Kaplan-Meier analysis, overall survival rates at 2 years were 96.2%, 75.2%, and 50.6% for patients in the lower, middle, and upper tertiles of sVCAM-1 levels, respectively (P < 0.0001). Fatal and nonfatal cardiovascular event-free survival rates were 58.2%, 56.9%, and 19.4% for patients in the lower, middle, and upper tertiles, respectively (P < 0.0001). Using Cox regression analysis with adjustment for confounding covariates, every 100-ng/mL increase in sVCAM-1 level was associated with 8% (95% confidence interval, 1.03 to 1.13) and 5% (95% confidence interval, 1.00 to 1.10) increases in risk for death and fatal and nonfatal cardiovascular events, respectively. Its significance for all-cause mortality remained with additional adjusting for LDL cholesterol level, but was lost when adjusting for residual GFR. Its association with cardiovascular events became insignificant when adjusting for LDL cholesterol level or residual GFR. Furthermore, patients with both sVCAM-1 and CRP levels elevated at the 50th percentile or greater were associated with the greatest death and fatal and nonfatal cardiovascular event rates compared with those with either CRP or sVCAM-1 level elevated at the 50th percentile or greater.

CONCLUSION

Circulating sVCAM-1 levels show an important link with residual renal function, LDL cholesterol level, and cardiac hypertrophy in CAPD patients. Furthermore, residual renal function, which correlates inversely with circulating sVCAM-1 level, shows an important association with all-cause mortality and cardiovascular events and displaces sVCAM-1 level from the models for all-cause mortality and future cardiovascular events in CAPD patients. Additional study is needed to explore possible mechanistic links between inflammation, soluble adhesion molecules, residual renal function, and cardiac hypertrophy in CAPD patients.

摘要

背景

血管细胞黏附分子1(VCAM - 1)参与白细胞与内皮细胞的相互作用,在炎症反应中起关键作用。其是否导致透析患者的过高死亡率仍不确定。在本研究中,我们检测了腹膜透析(PD)患者循环中可溶性VCAM - 1(sVCAM - 1)与不同临床和生化参数以及死亡率和心血管事件的关系。

方法

在研究基线时测定血清sVCAM - 1值以及C反应蛋白(CRP)、同型半胱氨酸、白蛋白、血脂谱、血红蛋白和透析充分性指标,并对160例长期PD患者进行超声心动图检查。患者平均随访35±16(标准差)个月。

结果

我们的持续性非卧床腹膜透析(CAPD)患者血清sVCAM - 1水平升高,与残余肾小球滤过率(GFR;P < 0.001)和低密度脂蛋白(LDL)胆固醇水平呈负相关(P = 0.004),但与左心室质量指数呈正相关(P = 0.025)。使用Kaplan - Meier分析,sVCAM - 1水平处于较低、中等和较高三分位数的患者2年总生存率分别为96.2%、75.2%和50.6%(P < 0.0001)。较低、中等和较高三分位数患者的无致命和非致命心血管事件生存率分别为58.2%、56.9%和19.4%(P < 0.0001)。使用Cox回归分析并对混杂协变量进行校正后,sVCAM - 1水平每升高100 ng/mL,死亡风险增加8%(95%置信区间,1.03至1.13),致命和非致命心血管事件风险增加5%(95%置信区间,1.00至1.10)。在进一步校正LDL胆固醇水平后,其对全因死亡率的意义仍然存在,但在校正残余GFR后其意义消失。在校正LDL胆固醇水平或残余GFR后,其与心血管事件的关联变得不显著。此外,与sVCAM - 1或CRP水平在第50百分位数或更高水平升高的患者相比,sVCAM - 1和CRP水平均在第50百分位数或更高水平升高的患者的死亡以及致命和非致命心血管事件发生率最高。

结论

循环sVCAM - 1水平与CAPD患者的残余肾功能、LDL胆固醇水平和心脏肥大密切相关。此外,与循环sVCAM - 1水平呈负相关的残余肾功能与全因死亡率和心血管事件密切相关,并在CAPD患者全因死亡率和未来心血管事件模型中取代了sVCAM - 1水平的地位。需要进一步研究以探索CAPD患者炎症、可溶性黏附分子、残余肾功能和心脏肥大之间可能的机制联系。

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