基于生物标志物的急性肾损伤亚表型可优化心脏手术患儿的风险评估。
Biomarker-based acute kidney injury sub-phenotypes refine risk assessment in children undergoing cardiac surgery.
作者信息
Pettit Kevin A, Melink Katherine F, Alten Jeffrey A, Goldstein Stuart L, Ollberding Nicholas, SooHoo Megan, Sullivan Emily, Zang Huaiyu, Stanski Natalja L, Gist Katja M
机构信息
Department of Pediatrics, Children's Hospital Colorado, University of Colorado Anschutz Medical Center, Aurora, CO, USA.
Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
出版信息
Pediatr Nephrol. 2025 Feb;40(2):523-531. doi: 10.1007/s00467-024-06541-z. Epub 2024 Sep 27.
BACKGROUND
Pediatric cardiac surgery-associated acute kidney injury (CS-AKI) is common with variable association with outcomes, possibly because transient serum creatinine (SCr) elevations are unrelated to kidney disease. Sub-phenotypes of CS-AKI with biomarker integration may provide prognostic enrichment. This study aims to determine if combining early postoperative urine neutrophil gelatinase-associated lipocalin (uNGAL) and SCr into sub-phenotypes strengthens associations with AKI and outcomes. We hypothesized that patients with early subclinical (uNGAL + , SCr -) or damage (uNGAL + , SCr +) CS-AKI would have more postoperative day 2-4 KDIGO-defined AKI and worse clinical outcomes than patients with early functional AKI (uNGAL - , SCr +).
METHODS
Two-center prospective observational study evaluating combinations of early uNGAL (8-12 h from ICU admission, ≥ 150 ng/mL) and early postoperative (≤ 8 h of admission) KDIGO SCr-defined AKI to predict CS-AKI on postoperative days (POD) 2-4. Four CS-AKI phenotypes were derived (uNGAL - /SCr - ; uNGAL + /SCr - ; uNGAL - /SCr + and uNGAL + /SCr +). The primary outcome was POD2-4 KDIGO SCr-defined CS-AKI. Secondary outcomes included ventilator and intensive care unit-free days (maximum 28).
RESULTS
Four hundred seventy-six patients (median age 4.8 [IQR 1.4-30.4] months, 39% female) were included. POD2-4 AKI occurred in 44 (9.2%). 27% were uNGAL + /SCr - and 0.4% (n = 2) uNGAL + /SCr + . The adjusted odds of POD2-4 AKI was ninefold higher (aOR: 9.09, 95%CI: 3.84-21.53) in uNGAL + /SCr - when compared to uNGAL - /SCr - . uNGAL + /SCr - was associated with fewer ventilator-free (aOR: 0.30, 95%CI: 0.19-0.48) and ICU-free days (aOR: 0.41, 95%CI: 0.26-0.66) when compared to uNGAL - /SCr - .
CONCLUSION
Early postoperative uNGAL, regardless of SCr elevation, refines risk assessment for pediatric POD2-4 CS-AKI and associated morbidity, enabling earlier AKI identification and prognostics.
背景
小儿心脏手术相关急性肾损伤（CS-AKI）很常见，其与预后的关联存在差异，这可能是因为血清肌酐（SCr）的短暂升高与肾脏疾病无关。整合生物标志物的CS-AKI亚表型可能会提供更丰富的预后信息。本研究旨在确定将术后早期尿中性粒细胞明胶酶相关脂质运载蛋白（uNGAL）和SCr结合到亚表型中是否会加强与急性肾损伤及预后的关联。我们假设，与早期功能性急性肾损伤（uNGAL-，SCr+）的患者相比，早期亚临床（uNGAL+，SCr-）或损伤性（uNGAL+，SCr+）CS-AKI的患者术后第2至4天发生KDIGO定义的急性肾损伤的情况更多，临床结局更差。
方法
一项两中心前瞻性观察性研究，评估早期uNGAL（从入住重症监护病房起8 - 12小时，≥150 ng/mL）和术后早期（入院≤8小时）KDIGO定义的SCr急性肾损伤的组合情况，以预测术后第2至4天（POD）的CS-AKI。得出了四种CS-AKI表型（uNGAL- /SCr-；uNGAL+ /SCr-；uNGAL- /SCr+和uNGAL+ /SCr+）。主要结局是POD2 - 4 KDIGO定义的SCr CS-AKI。次要结局包括无需呼吸机和无需重症监护病房的天数（最长28天）。
结果
纳入476例患者（中位年龄4.8 [四分位间距1.4 - 30.4]个月，39%为女性）。44例（9.2%）发生了POD2 - 4急性肾损伤。27%为uNGAL+ /SCr-，0.4%（n = 2）为uNGAL+ /SCr+。与uNGAL- /SCr-相比，uNGAL+ /SCr-发生POD2 - 4急性肾损伤的校正比值高9倍（校正比值比：9.09，95%置信区间：3.84 - 21.53）。与uNGAL- /SCr-相比，uNGAL+ /SCr-与更少的无需呼吸机天数（校正比值比：0.30，95%置信区间：0.19 - 0.48）和无需重症监护病房天数（校正比值比：0.41，95%置信区间：0.26 - 0.66）相关。
结论
术后早期uNGAL，无论SCr是否升高，都能优化小儿POD2 - 4 CS-AKI及相关发病率的风险评估，有助于更早地识别急性肾损伤并进行预后判断。
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