Acute tubular necrosis is associated with high mortality rates and it is important to develop new biomarkers for tubular damage. The aim of this study was to investigate the effect of early tubular damage on a large number of urinary cytokines, chemokines, and growth factors. We selected 90 urine samples from the Prospective Investigation of the Vasculature in Uppsala Seniors Study (41 males and 49 females). The tubular damage markers cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) were analyzed in the urine samples and urinary cytokine levels were analyzed with 2 multiplex assays (proximity extension assay). After adjustment for sex, body mass index, estimated glomerular filtration rate, smoking, and multiplicity testing using the false discovery rate approach, there remained 26 cytokines that correlated significantly with urine cystatin C, 27 cytokines that correlated with NGAL, and 66 cytokines that correlated with KIM-1. Tubular damage shows a strong association with urinary cytokines, chemokines, and growth factors. Our findings indicate that multiplex proteomics could be a promising new approach to explore the complex effects of tubular damage.

中文翻译：

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早期肾小管损伤与老年男性和女性的尿细胞因子、趋化因子和生长因子水平之间存在密切关联

急性肾小管坏死与高死亡率相关，因此开发新的肾小管损伤生物标志物非常重要。本研究的目的是调查早期肾小管损伤对大量尿细胞因子、趋化因子和生长因子的影响。我们从乌普萨拉老年人血管系统前瞻性调查研究中选择了 90 份尿液样本（41 名男性和 49 名女性）。对尿液样本中的肾小管损伤标志物胱抑素 C、中性粒细胞明胶酶相关脂质运载蛋白 (NGAL) 和肾损伤分子 1 (KIM-1) 进行了分析，并通过 2 种多重测定（接近延伸测定）分析了尿细胞因子水平。在对性别、体重指数、估计的肾小球滤过率、吸烟和使用错误发现率方法进行多重测试进行调整后，与尿胱抑素C显着相关的细胞因子有26个，与NGAL相关的细胞因子有27个，与KIM-1相关的细胞因子有66个。肾小管损伤与尿细胞因子、趋化因子和生长因子密切相关。我们的研究结果表明，多重蛋白质组学可能是探索肾小管损伤复杂影响的一种很有前途的新方法。