Mansell Holly, Soliman Mahmoud, Elmoselhi Hamdi, Shoker Ahmed
College of Pharmacy and Nutrition, University of Saskatchewan, Saskatchewan, Canada.
St. Paul's Hospital, Saskatchewan Renal Transplant Program, Saskatoon, SK, Canada.
PLoS One. 2015 Nov 6;10(11):e0142141. doi: 10.1371/journal.pone.0142141. eCollection 2015.
The Major Adverse Cardiovascular Events calculator (CRCRTR-MACE) estimates the burden of cardiovascular risk in renal transplant recipients (RTR). Our recent study of 95 RTR reported the 7-year median risk of cardiovascular events (CVE) to be 9.97%, ranging from 1.93 to 84.27%. Nearly a third (28.4%) of the cohort was above 20% risk for a CVE. Since interleukins (ILs) as part of the inflammatory response may play a role in the pathogenesis of cardiovascular disease (CVD), we extended this study to identify which ILs are associated with high cardiovascular risk in this population.
Twenty-two ILs were measured by multiplexed fluorescent bead-based immunoassay in 95 RTR and 56 normal controls. Stepwise analysis after multivariate determination of significant demographic and inflammatory variables was performed between the high and low-CVD risk groups (which were arbitrarily set at scores <10% and ≥20%, respectively). Normalized data was presented as mean ± SD and non-normalized data as median (minimum-maximum). Significance was measured at <0.05.
27.5% of the low-risk and 31.3% of the high-risk groups had mean IL levels above the 95 percentile of the normal control levels. In the non-parametric analysis IL-6, 9, 16, 17 and 33 were significantly higher in the high-risk group compared to the control. Univariate analysis (UVA) of the high-risk group identified IL-33 as the only IL that remained significantly higher than the control and low-risk groups (p = 0.000). The percentage of patients with IL-33 levels above the 90 percentile of control value in the low and high-risk groups were 15.6% and 52.0%, respectively (p<0.002). UVA of factors significant to high IL-33 levels included estimated glomerular filtration rate (eGFR), while diabetes mellitus, serum phosphorus, microalbuminuria and age also remained significant in the multivariate analysis.
Circulating IL-33 level is positively associated with high CRCRTR-MACE score. Diminished eGFR, age, diabetes, serum phosphorus and microalbuminurea demonstrate significant relationship with elevated IL-33 levels, supporting the possible pathognomonic role of IL-33 in the cardiovascular burden in RTR.
主要不良心血管事件计算器（CRCRTR-MACE）用于评估肾移植受者（RTR）的心血管疾病风险负担。我们最近对95名RTR进行的研究报告称，心血管事件（CVE）的7年中位风险为9.97%，范围在1.93%至84.27%之间。该队列中近三分之一（28.4%）的患者发生CVE的风险高于20%。由于作为炎症反应一部分的白细胞介素（IL）可能在心血管疾病（CVD）的发病机制中起作用，我们扩展了这项研究，以确定哪些IL与该人群的高心血管风险相关。
采用基于多重荧光微珠的免疫测定法，对95名RTR和56名正常对照者检测了22种IL。在高CVD风险组和低CVD风险组（分别任意设定为评分<10%和≥20%）之间，对显著的人口统计学和炎症变量进行多变量测定后进行逐步分析。标准化数据以平均值±标准差表示，非标准化数据以中位数（最小值 - 最大值）表示。显著性水平设定为<0.05。
低风险组中27.5%和高风险组中31.3%的患者平均IL水平高于正常对照水平的第95百分位数。在非参数分析中，高风险组的IL-6、9、16、17和33显著高于对照组。高风险组的单因素分析（UVA）确定IL-33是唯一显著高于对照组和低风险组的IL（p = 0.000）。低风险组和高风险组中IL-33水平高于对照值第90百分位数的患者百分比分别为15.6%和52.0%（p<0.002）。对高IL-33水平有显著影响的因素的UVA分析包括估计肾小球滤过率（eGFR），而在多变量分析中，糖尿病、血清磷、微量白蛋白尿和年龄也仍然具有显著性。
循环IL-33水平与高CRCRTR-MACE评分呈正相关。eGFR降低、年龄、糖尿病、血清磷和微量白蛋白尿与IL-33水平升高显著相关，支持IL-33在RTR心血管负担中可能具有的病理诊断作用。
