Del Toro-Cisneros Noemí, Páez-Franco José C, Martínez-Rojas Miguel A, González-Soria Isaac, Ortega-Trejo Juan Antonio, Sánchez-Vidal Hilda, Bobadilla Norma A, Ulloa-Aguirre Alfredo, Vega-Vega Olynka
Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico.
Red de Apoyo a la Investigación, Universidad Nacional Autónoma de México, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico.
Diagnostics (Basel). 2025 Aug 5;15(15):1960. doi: 10.3390/diagnostics15151960.
: COVID-19 is a systemic viral infection that may lead to serious complications including acute kidney injury that requires kidney replacement therapy. The primary aim of this study was to evaluate urinary SerpinA3 (uSerpinA3) excretion as a biomarker of kidney recovery at 90 days, and the mortality in patients with critical COVID-19 and AKI requiring kidney replacement therapy (KRT). : The study included patients with critical COVID-19 on invasive mechanical ventilation (IMV) requiring KRT. Blood and urine samples were obtained when KRT was initiated (day zero), and thereafter on days 1, 3, 7, and 14 post-replacement. uSerpinA3, kidney injury molecule-1 (uKIM-1), and neutrophil gelatinase-associated lipocalin (uNGAL) were measured in urine, and interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor alpha (TNF-α) in peripheral blood. In addition, metabolomics in sample days zero and 3, and in the survivors on sample day 90 was performed by employing gas chromatography coupled with mass spectrometry. : A total of 60 patients were recruited, of whom 29 (48%) survived hospitalization and recovered kidney function by day 90. In the survivors, 79% presented complete recovery (CRR) and the remaining (21%) recovered partially (PRR). In terms of uSerpinA3, levels on days 7 and 14 predicted CRR, with AUC values of 0.68 ( = 0.041) and 0.71 ( = 0.030), respectively, as well as mortality, with AUC values of 0.75 ( = 0.007) and 0.76 ( = 0.015), respectively. Among the other biomarkers, the excretion of uKIM-1 on day zero of KRT had a superior performance as a CRR predictor [(AUC, 0.71 ( = 0.017)], and as a mortality predictor [AUC, 0.68 ( = 0.028)]. In the metabolomics analysis, we identified four distinct profiles; the metabolite that maintained statistical significance in predicting mortality was p-cresol glucuronide. : This study strongly suggests that uSerpinA3 and uKIM-1 can predict CRR and mortality in patients with critical COVID-19 and AKI requiring KRT. Metabolic analysis appears promising for identifying affected pathways and their clinical impact in this population.
新型冠状病毒肺炎（COVID-19）是一种全身性病毒感染，可能导致严重并发症，包括需要肾脏替代治疗的急性肾损伤。本研究的主要目的是评估尿丝氨酸蛋白酶抑制剂A3（uSerpinA3）排泄作为90天时肾脏恢复的生物标志物，以及评估患有重症COVID-19和急性肾损伤且需要肾脏替代治疗（KRT）患者的死亡率。：该研究纳入了接受有创机械通气（IMV）且需要KRT的重症COVID-19患者。在开始KRT时（第0天）采集血液和尿液样本，此后在置换后的第1、3、7和14天采集样本。检测尿液中的uSerpinA3、肾损伤分子-1（uKIM-1）和中性粒细胞明胶酶相关脂质运载蛋白（uNGAL），以及外周血中的白细胞介素-6（IL-6）、白细胞介素-10（IL-10）和肿瘤坏死因子α（TNF-α）。此外，采用气相色谱-质谱联用技术对第0天和第3天的样本以及第90天存活患者的样本进行代谢组学分析。：共招募了60名患者，其中29名（48%）存活至出院，且在90天时肾功能恢复。在存活患者中，79%呈现完全恢复（CRR），其余（21%）部分恢复（PRR）。就uSerpinA3而言，第7天和第14天的水平可预测CRR，AUC值分别为0.68（P = 0.041）和0.71（P = 0.030），也可预测死亡率，AUC值分别为0.75（P = 0.007）和0.76（P = 0.015）。在其他生物标志物中，KRT第0天uKIM-1的排泄作为CRR预测指标表现更优[（AUC，0.71（P = 0.017）]，作为死亡率预测指标也更优[AUC，0.68（P = 0.028）]。在代谢组学分析中，我们确定了四种不同的特征；在预测死亡率方面保持统计学意义的代谢物是对甲酚葡萄糖醛酸苷。：本研究强烈表明，uSerpinA3和uKIM-1可预测患有重症COVID-19和急性肾损伤且需要KRT患者的CRR和死亡率。代谢分析在识别该人群中受影响的途径及其临床影响方面似乎很有前景。
