Markers of kidney tubule function and risk of cardiovascular disease events and mortality in the SPRINT trial
Markers of kidney tubule function and risk of cardiovascular disease events and mortality in the SPRINT trial
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DOI：
10.1093/eurheartj/ehz392
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发表时间：
2019-11-07
影响因子：
39.3
通讯作者：
Shlipak, Michael G.
中科院分区：
文献类型：
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作者：
Garimella, Pranav S.;Lee, Alexandra K.;Shlipak, Michael G.
肾小管损伤、炎症和纤维化的生物标志物已被广泛研究，并被确立为肾脏和心血管疾病（CVD）不良结局的危险标志物。然而，肾小管功能标志物与不良临床事件的关系尚未得到很好的研究，特别是在慢性肾脏疾病（CKD）患者中。方法和结果在基线收缩压干预试验（SPRINT）访问时，我们使用2377例CKD患者的样本，评估了三种尿管功能标志物，α -1微球蛋白（α 1m）， β -2微球蛋白（β 2m）和尿调素与复合CVD终点(心肌梗死，急性冠状动脉综合征，中风，急性失代偿性心力衰竭，使用Cox比例风险回归，调整基线估计肾小球滤过率（eGFR）、蛋白尿和心血管疾病危险因素。在未调整的分析中，在中位3.8年的随访中，α 1m和β 2m与复合心血管事件和死亡率呈正相关，而尿调素与这两种结果的风险呈负相关。在包括eGFR和蛋白尿在内的多变量分析中，α - 1m基线浓度高出两倍与CVD的高风险相关[危险比（HR） 1.25；95%可信区间（CI）： 1.10-1.45)和死亡率（HR 1.25; 95% CI: 1.10-1.46），而β 2m与两种结果均无关联。两倍高的尿调素浓度与较低的心血管疾病风险相关（HR 0.79; 95% CI: 0.68-0.90），但与死亡率无关（HR 0.86; 95% CI: 0.73-1.01）。结论在非糖尿病CKD患者中，小管功能的生物标志物与CVD事件和死亡率相关，与肾小球功能和蛋白尿无关。
Aims Biomarkers of kidney tubule injury, inflammation and fibrosis have been studied extensively and established as risk markers of adverse kidney and cardiovascular disease (CVD) outcomes. However, associations of markers of kidney tubular function with adverse clinical events have not been well studied, especially in persons with chronic kidney disease (CKD).Methods and results Using a sample of 2377 persons with CKD at the baseline Systolic Blood Pressure Intervention Trial (SPRINT) visit, we evaluated the association of three urine tubular function markers, alpha-1 microglobulin (alpha 1m), beta-2 microglobulin (beta 2m), and uromodulin, with a composite CVD endpoint (myocardial infarction, acute coronary syndrome, stroke, acute decompensated heart failure, or death from cardiovascular causes) and mortality using Cox proportional hazards regression, adjusted for baseline estimated glomerular filtration rate (eGFR), albuminuria, and CVD risk factors. In unadjusted analysis, over a median follow-up of 3.8years, alpha 1m and beta 2m had positive associations with composite CVD events and mortality, whereas uromodulin had an inverse association with risk for both outcomes. In multivariable analysis including eGFR and albuminuria, a two-fold higher baseline concentration of alpha 1m was associated with higher risk of CVD [hazard ratio (HR) 1.25; 95% confidence interval (CI): 1.10-1.45] and mortality (HR 1.25; 95% CI: 1.10-1.46), whereas beta 2m had no association with either outcome. A two-fold higher uromodulin concentration was associated with lower CVD risk (HR 0.79; 95% CI: 0.68-0.90) but not mortality (HR 0.86; 95% CI: 0.73-1.01) after adjusting for similar confounders.Conclusion Among non-diabetic persons with CKD, biomarkers of tubular function are associated with CVD events and mortality independent of glomerular function and albuminuria.