Urinary Biomarkers of Tubular Damage Are Associated with Mortality but Not Cardiovascular Risk among Systolic Blood Pressure Intervention Trial Participants with Chronic Kidney Disease
Urinary Biomarkers of Tubular Damage Are Associated with Mortality but Not Cardiovascular Risk among Systolic Blood Pressure Intervention Trial Participants with Chronic Kidney Disease
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DOI：
10.1159/000499531
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发表时间：
2019-01-01
影响因子：
4.2
通讯作者：
Ix, Joachim H.
中科院分区：
文献类型：
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作者：
Jotwani, Vasantha K.;Lee, Alexandra K.;Ix, Joachim H.
背景：肾活检的肾小管间质纤维化是慢性肾脏病(CKD)进展的有力预测指标，CKD与心血管疾病(CVD)的风险增加相关。传统的肾功能指标，包括估计的肾小球滤过率(EGFR)和蛋白尿，很难量化肾小管的健康状况。我们假设肾小管损伤、炎症和修复的尿液生物标志物与慢性肾脏病患者心血管疾病和死亡率的高风险相关。方法：测定2377例血压干预试验受试者基础尿液中白介素18(IL-18)、肾损伤分子-1、中性粒细胞明胶酶相关脂钙蛋白、单核细胞趋化蛋白-1和几丁质酶-3样蛋白-1(YKL-40)的浓度。我们使用COX比例风险模型来评估生物标记物与心血管事件和全因死亡率的关系。结果：基线时，参与者的平均年龄为72+/-9岁，EGFR为48+/-11毫升/分钟/1.73米(2)。在中位数3.8年的随访中，发生了305例心血管事件(每年3.6%)和233例全因死亡(每年2.6%)。在调整了包括EGFR、蛋白尿和尿肌酐在内的多个变量后，没有一个生物标志物与心血管疾病风险有统计学意义的相关性。尿IL-18(危险比高2倍，危险比1.14；95%可信区间1.01-1.29)和YKL-40浓度(危险比高2倍，危险比1.08；95%可信区间1.02-1.14)均与较高的死亡风险呈递增相关。当按随机血压组分层时，相关性相似。结论：在患有CKD的高血压试验参与者中，尿中IL-18和YKL-40的升高与更高的死亡风险相关，但与心血管疾病无关。(C)2019年S.Karger AG，巴塞尔。
Background: Kidney tubulointerstitial fibrosis on biopsy is a strong predictor of chronic kidney disease (CKD) progression, and CKD is associated with elevated risk of cardiovascular disease (CVD). Tubular health is poorly quantified by traditional kidney function measures, including estimated glomerular filtration rate (eGFR) and albuminuria. We hypothesized that urinary biomarkers of tubular injury, inflammation, and repair would be associated with higher risk of CVD and mortality in persons with CKD. Methods: We measured urinary concentra-tions of interleukin-18 (IL-18), kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, monocyte chemoattractant protein-1, and chitinase-3-like protein-1 (YKL-40) at baseline among 2,377 participants of the Systolic Blood Pressure Intervention Trial who had an eGFR < 60 mL/min/1.73 m(2). We used Cox proportional hazards models to evaluate biomarker associations with CVD events and all-cause mortality. Results: At baseline, the mean age of participants was 72 +/- 9 years, and eGFR was 48 +/- 11 mL/min/1.73 m(2). Over a median follow-up of 3.8 years, 305 CVD events (3.6% per year) and 233 all-cause deaths (2.6% per year) occurred. After multivariable adjustment including eGFR, albuminuria, and urinary creatinine, none of the biomarkers showed statistically significant associations with CVD risk. Urinary IL-18 (hazard ratio [HR] per 2-fold higher value, 1.14; 95% CI 1.01-1.29) and YKL-40 (HR per 2-fold higher value, 1.08; 95% CI 1.02-1.14) concentrations were each incrementally associated with higher mortality risk. Associations were similar when stratified by randomized blood pressure arm. Conclusions: Among hypertensive trial participants with CKD, higher urinary IL-18 and YKL-40 were associated with higher risk of mortality, but not CVD. (c) 2019 S. Karger AG, Basel.