脓毒性休克患儿肾损伤生物标志物的时间进程：脓毒症试验中平衡液与生理盐水实用儿科试验中的嵌套队列研究
Time Course of Kidney Injury Biomarkers in Children With Septic Shock: Nested Cohort Study Within the Pragmatic Pediatric Trial of Balanced Versus Normal Saline Fluid in Sepsis Trial.
作者信息
Weiss Scott L, Fitzgerald Julie C, Laskin Benjamin L, Singh Ruchi, Artis Amanda S, Vohra Ananya, Tsemberis Elena, Kierian Emem, Lau Kristen C, Campos Atzael B, Hickey Christopher, Hayes Katie L, Singleton Daniel, Long Elliot, Babl Franz E, Dalziel Stuart R, Thompson Graham C, Freedman Stephen B, Eckerle Michelle, Hickey Robert W, Huang Jing, Kuppermann Nathan, Balamuth Fran
机构信息
Division of Critical Care, Department of Pediatrics, Nemours Children's Hospital, Wilmington, DE.
Departments of Pediatrics and Pathology, Anatomy, and Cell Biology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA.
出版信息
Pediatr Crit Care Med. 2025 Jun 1;26(6):e816-e826. doi: 10.1097/PCC.0000000000003737. Epub 2025 Apr 2.
OBJECTIVE
Severe acute kidney injury (AKI) portends poor outcomes in pediatric sepsis. We evaluated the trajectory and prognostic utility of AKI biomarkers in pediatric septic shock using a subset of participants in the ongoing Pragmatic Pediatric Trial of Balanced vs. Normal Saline Fluid in Sepsis (PRoMPT BOLUS) trial, NCT04102371. We tested whether fluid volume is associated with persistent elevation of urine neutrophil gelatinase-associated lipocalin (Ur-NGAL).
DESIGN
Prospective, non-prespecified cohort study within the PRoMPT BOLUS trial.
SETTING
Three children's hospitals in the United States.
PATIENTS
Four hundred seventy-eight patients aged 2 months to younger than 18 years old with septic shock.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
Ur-NGAL, kidney injury molecule-1, liver fatty acid binding protein, and interleukin-18 and plasma cystatin C were collected at presentation (T1), days 2-3 (T2), and before discharge/death (T3). At presentation, 418 (88%) had no or only stage 1 AKI and 60 (12%) had stage 2/3 AKI defined using Kidney Disease Improving Global Outcomes creatinine thresholds. All biomarkers were higher with stage 2/3 compared with no/stage 1 AKI at T1 and T2, but only cystatin C remained higher at T3. Among patients with no/stage 1 AKI at presentation, those with Ur-NGAL greater than or equal to 150 vs. less than 150 ng/mL had fewer hospital-free days (21 [interquartile range (IQR) 15-24] vs. 23 d [IQR 19-25], p = 0.05). After applying inverse probability treatment weighting to balance covariates, 14% of patients who received greater than 100 mL/kg within 48 hours had persistently elevated Ur-NGAL over time compared with 6% who received 40-100 mL/kg (odds ratio 2.7 [95% CI, 1.1-6.2]). Hospital-free days were no different across fluid volume groups.
CONCLUSIONS
Although kidney injury biomarkers mirrored serum creatinine in children with septic shock, elevated Ur-NGAL identified a subset with subclinical AKI with fewer hospital-free days despite no/stage 1 AKI by creatinine. Children receiving greater than 100 mL/kg fluid had greater odds of early and persistently elevated Ur-NGAL, suggesting high fluid volumes may perpetuate initial kidney damage.
目的
严重急性肾损伤（AKI）预示着小儿脓毒症的不良预后。我们利用正在进行的脓毒症平衡与生理盐水实用儿科试验（PRoMPT BOLUS）试验（NCT04102371）的一部分参与者，评估了AKI生物标志物在小儿感染性休克中的变化轨迹及预后效用。我们测试了液体量是否与尿中性粒细胞明胶酶相关脂质运载蛋白（Ur-NGAL）持续升高有关。
设计
PRoMPT BOLUS试验中的前瞻性、非预先指定队列研究。
地点
美国的三家儿童医院。
患者
478例年龄在2个月至18岁以下的感染性休克患者。
干预措施
无。
测量指标及主要结果
在入院时（T1）、第2 - 3天（T2）以及出院/死亡前（T3）收集Ur-NGAL、肾损伤分子-1、肝脂肪酸结合蛋白、白细胞介素-18和血浆胱抑素C。入院时，418例（88%）无AKI或仅有1期AKI，60例（12%）根据改善全球肾脏病预后组织的肌酐阈值定义为2/3期AKI。在T1和T2时，与无/1期AKI相比，所有生物标志物在2/3期时均更高，但在T3时只有胱抑素C仍较高。在入院时无/1期AKI的患者中，Ur-NGAL大于或等于150 ng/mL与小于150 ng/mL的患者相比，无住院天数更少（分别为21天[四分位间距（IQR）15 - 24]和23天[IQR 19 - 25]，p = 0.05）。在应用逆概率处理加权以平衡协变量后，48小时内接受大于100 mL/kg液体的患者中，14%的患者Ur-NGAL随时间持续升高，而接受40 - 100 mL/kg液体的患者中这一比例为6%（优势比2.7[95% CI，1.1 - 6.2]）。不同液体量组的无住院天数无差异。
结论
尽管肾损伤生物标志物在感染性休克儿童中与血清肌酐变化趋势一致，但Ur-NGAL升高识别出了一部分亚临床AKI患者，尽管根据肌酐标准为无/1期AKI，但无住院天数较少。接受大于100 mL/kg液体的儿童早期和持续Ur-NGAL升高的可能性更大，提示高液体量可能使初始肾损伤持续存在。
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