Mansell Holly, Elmoselhi Hamdi, Shoker Ahmed
College of Pharmacy and Nutrition, University of Saskatchewan, Saskatchewan, Canada.
Am J Nephrol. 2015;41(2):147-55. doi: 10.1159/000377641. Epub 2015 Mar 19.
BACKGROUND/AIMS: The 7-year Major Adverse Cardiovascular Events Calculator (CRCRTR-MACE) predicts cardiovascular events (CVE) in renal transplant recipients (RTR), and thrombopoietin (TPO) is a humoral inflammatory factor implicated in cardiovascular disease (CVD). The aim of the study was to determine if circulating TPO levels in stable RTR are positively associated with variable(s) in the CRCRTR-MACE score.
CRCRTR-MACE scores were calculated in 95 stable RTR. TPO levels were measured by multiplexed fluorescent bead-based immunoassay in all patients and 48 controls. Multivariate analysis (MVA) was performed between TPO and CV risk variables and patient demographics. Stepwise regression with backward elimination of insignificant variables estimated the impact of risk variables on TPO levels. Significance was defined at p < 0.05. Normalized data were presented as mean ± SD and non-normalized data as median (maximum to minimum).
The risk of a CVE within 7 years as predicted by the median was 9.97% (range 1.93-84.2). The percentage of patients who were above 20% risk for a CVE was 28.4%. Control TPO level of 170.41 (4.4-995.9) pg/ml was significantly lower than that of 237.90 (32.77-1,386.79) pg/ml in RTR (p = 0.010). TPO level correlated significantly with the total CRCRTR-MACE score (R = 0.310, p = 0.004), smoking (p = 0.009) and eGFR (R = -0.275, p = 0.012) but not with age, diabetes, LDL level or history of CVE. Only the total CRCRTR-MACE score (p = 0.013) and smoking (p = 0.009) remained significant in the MVA. Stepwise regression estimated that smoking increased TPO levels by 206.28 pg/ml and each 10% increase in CRCRTR-MACE score increased TPO levels by an additional 44.4 pg/ml.
TPO levels are increased in RTR with high CRCRTR-MACE, particularly in smokers with diminished eGFR. Circulating TPO may serve as a biomarker and treatment target for CVD in RTR.
背景/目的：7年主要不良心血管事件计算器（CRCRTR-MACE）可预测肾移植受者（RTR）的心血管事件（CVE），而血小板生成素（TPO）是一种与心血管疾病（CVD）相关的体液炎症因子。本研究的目的是确定稳定RTR中循环TPO水平是否与CRCRTR-MACE评分中的变量呈正相关。
计算95例稳定RTR的CRCRTR-MACE评分。采用基于多重荧光微珠的免疫分析法测定所有患者和48例对照的TPO水平。对TPO与心血管风险变量及患者人口统计学数据进行多变量分析（MVA）。通过逐步回归并剔除无显著意义的变量来估计风险变量对TPO水平的影响。显著性定义为p<0.05。标准化数据以均值±标准差表示，非标准化数据以中位数（最大值到最小值）表示。
中位数预测的7年内发生CVE的风险为9.97%（范围1.93 - 84.2）。CVE风险高于20%的患者比例为28.4%。对照组TPO水平为170.41（4.4 - 995.9）pg/ml，显著低于RTR组的237.90（32.77 - 1386.79）pg/ml（p = 0.010）。TPO水平与CRCRTR-MACE总分（R = 0.310，p = 0.004）、吸烟（p = 0.009）和估算肾小球滤过率（eGFR）（R = -0.275，p = 0.012）显著相关，但与年龄、糖尿病、低密度脂蛋白水平或CVE病史无关。在MVA中，只有CRCRTR-MACE总分（p = 0.013）和吸烟（p = 0.009）仍具有显著性。逐步回归估计，吸烟使TPO水平升高206.28 pg/ml，CRCRTR-MACE评分每增加10%，TPO水平额外升高44.4 pg/ml。
CRCRTR-MACE评分高的RTR中TPO水平升高，尤其是eGFR降低的吸烟者。循环TPO可能作为RTR中CVD的生物标志物和治疗靶点。
