急性肾损伤的临床和生物标志物数据联合建模定义了具有不同结局的独特亚表型。
Joint Modeling of Clinical and Biomarker Data in Acute Kidney Injury Defines Unique Subphenotypes with Differing Outcomes.
机构信息
Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Mount Sinai Clinical Intelligence Center, Icahn School of Medicine at Mount Sinai, New York, New York.
出版信息
Clin J Am Soc Nephrol. 2023 Jun 1;18(6):716-726. doi: 10.2215/CJN.0000000000000156. Epub 2023 Mar 28.
BACKGROUND
AKI is a heterogeneous syndrome. Current subphenotyping approaches have only used limited laboratory data to understand a much more complex condition.
METHODS
We focused on patients with AKI from the Assessment, Serial Evaluation, and Subsequent Sequelae in AKI (ASSESS-AKI). We used hierarchical clustering with Ward linkage on biomarkers of inflammation, injury, and repair/health. We then evaluated clinical differences between subphenotypes and examined their associations with cardiorenal events and death using Cox proportional hazard models.
RESULTS
We included 748 patients with AKI: 543 (73%) of them had AKI stage 1, 112 (15%) had AKI stage 2, and 93 (12%) had AKI stage 3. The mean age (±SD) was 64 (13) years; 508 (68%) were men; and the median follow-up was 4.7 (Q1: 2.9, Q3: 5.7) years. Patients with AKI subphenotype 1 ( N =181) had the highest kidney injury molecule (KIM-1) and troponin T levels. Subphenotype 2 ( N =250) had the highest levels of uromodulin. AKI subphenotype 3 ( N =159) comprised patients with markedly high pro-brain natriuretic peptide and plasma tumor necrosis factor receptor-1 and -2 and low concentrations of KIM-1 and neutrophil gelatinase-associated lipocalin. Finally, patients with subphenotype 4 ( N =158) predominantly had sepsis-AKI and the highest levels of vascular/kidney inflammation (YKL-40, MCP-1) and injury (neutrophil gelatinase-associated lipocalin, KIM-1). AKI subphenotypes 3 and 4 were independently associated with a higher risk of death compared with subphenotype 2 and had adjusted hazard ratios of 2.9 (95% confidence interval, 1.8 to 4.6) and 1.6 (95% confidence interval, 1.01 to 2.6, P = 0.04), respectively. Subphenotype 3 was also independently associated with a three-fold risk of CKD and cardiovascular events.
CONCLUSIONS
We discovered four AKI subphenotypes with differing clinical features and biomarker profiles that are associated with longitudinal clinical outcomes.
背景
急性肾损伤（AKI）是一种异质性综合征。目前的亚表型方法仅使用有限的实验室数据来了解更为复杂的情况。
方法
我们关注来自 AKI 的评估、连续评估和随后的 AKI 后遗症（ASSESS-AKI）的 AKI 患者。我们使用基于 Ward 链接的层次聚类对炎症、损伤和修复/健康的生物标志物进行分析。然后，我们评估了亚表型之间的临床差异，并使用 Cox 比例风险模型检查了它们与心肾事件和死亡的关联。
结果
我们纳入了 748 名 AKI 患者：543 名（73%）为 AKI 1 期，112 名（15%）为 AKI 2 期，93 名（12%）为 AKI 3 期。平均年龄（±标准差）为 64（13）岁；508 名（68%）为男性；中位随访时间为 4.7（Q1：2.9，Q3：5.7）年。AKI 亚表型 1（N=181）患者的肾损伤分子（KIM-1）和肌钙蛋白 T 水平最高。亚表型 2（N=250）的尿调蛋白水平最高。AKI 亚表型 3（N=159）由显著高的脑利钠肽前体、血浆肿瘤坏死因子受体-1 和 -2 以及低浓度的 KIM-1 和中性粒细胞明胶酶相关脂质运载蛋白组成。最后，亚表型 4（N=158）的患者主要患有脓毒症相关 AKI，其血管/肾脏炎症（YKL-40、MCP-1）和损伤（中性粒细胞明胶酶相关脂质运载蛋白、KIM-1）水平最高。与亚表型 2 相比，AKI 亚表型 3 和 4 与更高的死亡风险独立相关，调整后的危险比分别为 2.9（95%置信区间，1.8 至 4.6）和 1.6（95%置信区间，1.01 至 2.6，P=0.04）。亚表型 3 也与 CKD 和心血管事件的三倍风险独立相关。
结论
我们发现了四种具有不同临床特征和生物标志物特征的 AKI 亚表型，它们与纵向临床结局相关。
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