Holthoff Joseph Hunter, Alge Joseph L, Arthur John M, Ayub Fatima, Bin Homam Wadhah, Janech Michael G, Ravula Sreelakshmi, Karakala Nithin
Department of Nephrology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA,
Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, USA,
Nephron. 2025;149(2):66-76. doi: 10.1159/000540664. Epub 2024 Sep 30.
Acute kidney injury (AKI) is associated with adverse outcomes, including death and dialysis. The goal of this study was to identify prognostic biomarkers of AKI that could be used across multiple phenotypes of AKI and across different species.
Liquid chromatography/tandem mass spectrometry analysis of urine samples from three species (human, rat, and mouse) and four etiologies of AKI identified five potential biomarkers, of which two were validated, complement C3 and vitamin D-binding protein, in a cohort of 157 patients that developed AKI following cardiothoracic surgery. We studied the relationship between the biomarker's concentration in the urine and the development of a composite primary endpoint (stage 3 AKI within 10 days or death within 30 days).
Of the 153 patients who developed AKI following cardiovascular surgery, 17 met the combined primary outcome. The median concentration of urine complement C3 adjusted to urine creatinine had the best predictive value and was significantly higher in the primary outcome group than in the controls. Similarly, the median concentration of vitamin D-binding protein was higher in the primary outcome group.
The studies provide proof in principle that cross-species discovery analyses could be a valuable tool for identifying novel prognostic biomarkers in AKI. Urine complement C3 and vitamin D-binding protein could be promising early predictors of adverse outcomes in patients who develop AKI after cardiac surgery.
急性肾损伤（AKI）与不良后果相关，包括死亡和透析。本研究的目的是确定可用于多种AKI表型及不同物种的AKI预后生物标志物。
对来自三种物种（人类、大鼠和小鼠）的尿液样本以及AKI的四种病因进行液相色谱/串联质谱分析，确定了五种潜在生物标志物，其中两种在157例心胸外科手术后发生AKI的患者队列中得到验证，即补体C3和维生素D结合蛋白。我们研究了尿液中生物标志物浓度与复合主要终点（10天内发生3期AKI或30天内死亡）发生之间的关系。
在153例心血管手术后发生AKI的患者中，17例符合联合主要结局。调整为尿肌酐后的尿补体C3中位数浓度具有最佳预测价值，且在主要结局组中显著高于对照组。同样，主要结局组中维生素D结合蛋白的中位数浓度也更高。
这些研究原则上证明，跨物种发现分析可能是识别AKI新预后生物标志物的有价值工具。尿补体C3和维生素D结合蛋白可能是心脏手术后发生AKI患者不良结局的有前景的早期预测指标。
