Division of Systems Biology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, Arkansas.
Division of Biostatistics, Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia.
Kidney360. 2021 Nov 25;2(11):1716-1727. doi: 10.34067/KID.0002642021.
AKI requiring dialysis (AKI-D) is associated with prolonged hospitalization, mortality, and progressive CKD among survivors. Previous studies have examined only select urine or serum biomarkers for predicting kidney recovery from AKI.
Serum samples collected on day 8 of randomized RRT from 72 patients enrolled in the Veteran's Affairs/National Institutes of Health Acute Renal Failure Trial Network study were analyzed by the SOMAscan proteomic platform to profile 1305 proteins in each sample. Of these patients, 38 recovered kidney function and dialysis was discontinued, whereas another 34 patients remained on dialysis by day 28.
Differential serum levels of 119 proteins, with 53 higher and 66 lower, were detected in samples from patients who discontinued dialysis, compared with patients who remained on dialysis by day 28. Patients were classified into tertiles on the basis of SOMAscan protein measurements for the 25 proteins most differentially expressed. The association of serum levels of each protein with kidney recovery was further evaluated using logistic regression analysis. Higher serum levels of CXCL11, CXCL2/CXCL3, CD86, Wnt-7a, BTK, c-Myc, TIMP-3, CCL5, ghrelin, PDGF-C, survivin, CA2, IL-9, EGF, and neuregulin-1, and lower levels of soluble CXCL16, IL1RL1, stanniocalcin-1, IL-6, and FGF23 when classified in tertiles were significantly associated with better kidney recovery. This significant association persisted for each of these proteins after adjusting for potential confounding risk factors including age, sex, cardiovascular SOFA score, congestive heart failure, diabetes, modality of intensive dialysis treatment, cause of AKI, baseline serum creatinine, day 8 urine volume, and estimated 60-day mortality risk.
These results suggest concerted changes between survival-related proteins and immune-regulatory chemokines in regulating angiogenesis, endothelial and epithelial remodeling, and kidney cell regeneration, illustrating potential mechanisms of kidney recovery. Thus, this study identifies potential novel predictive biomarkers of kidney recovery in patients with AKI-D.
需要透析的急性肾损伤（AKI-D）与幸存者的住院时间延长、死亡率和进行性慢性肾脏病（CKD）有关。以前的研究仅检查了选定的尿液或血清生物标志物，以预测 AKI 的肾脏恢复。
从退伍军人事务部/美国国立卫生研究院急性肾衰竭试验网络研究中纳入的 72 例接受随机肾脏替代治疗的患者第 8 天的血清样本，通过 SOMAscan 蛋白质组学平台进行分析，以对每个样本中的 1305 种蛋白质进行分析。在这些患者中，38 例恢复了肾功能并停止透析，而另外 34 例在第 28 天仍在透析。
与第 28 天仍在透析的患者相比，停止透析的患者的血清中检测到 119 种蛋白的差异表达，其中 53 种蛋白的水平升高，66 种蛋白的水平降低。根据 SOMAscan 蛋白测量值，将 25 种表达差异最显著的蛋白分为 3 组。使用逻辑回归分析进一步评估了每种蛋白的血清水平与肾脏恢复的相关性。当分类为 tertiles 时，血清中更高水平的 CXCL11、CXCL2/CXCL3、CD86、Wnt-7a、BTK、c-Myc、TIMP-3、CCL5、ghrelin、PDGF-C、survivin、CA2、IL-9、EGF 和神经调节蛋白-1，以及较低水平的可溶性 CXCL16、IL1RL1、stanniocalcin-1、IL-6 和 FGF23，与更好的肾脏恢复显著相关。在调整年龄、性别、心血管 SOFA 评分、充血性心力衰竭、糖尿病、强化透析治疗方式、AKI 病因、基线血清肌酐、第 8 天尿量和估计 60 天死亡率等潜在混杂风险因素后，这些显著相关性仍然存在。
这些结果表明，与生存相关的蛋白和免疫调节趋化因子之间的协同变化，调节血管生成、内皮和上皮重塑以及肾脏细胞再生，说明了肾脏恢复的潜在机制。因此，本研究确定了 AKI-D 患者肾脏恢复的潜在新型预测生物标志物。
