血浆前脑啡肽和中性粒细胞明胶酶相关脂质运载蛋白对心源性休克急性肾损伤及死亡率的预测价值
Predictive value of plasma proenkephalin and neutrophil gelatinase-associated lipocalin in acute kidney injury and mortality in cardiogenic shock.
作者信息
Jäntti Toni, Tarvasmäki Tuukka, Harjola Veli-Pekka, Pulkki Kari, Turkia Heidi, Sabell Tuija, Tolppanen Heli, Jurkko Raija, Hongisto Mari, Kataja Anu, Sionis Alessandro, Silva-Cardoso Jose, Banaszewski Marek, DiSomma Salvatore, Mebazaa Alexandre, Haapio Mikko, Lassus Johan
机构信息
Department of Cardiology, Heart and Lung Center, Helsinki University Hospital, University of Helsinki, 00029 HUS, Helsinki, Finland.
Emergency Medicine, Department of Emergency Medicine and Services, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
出版信息
Ann Intensive Care. 2021 Feb 5;11(1):25. doi: 10.1186/s13613-021-00814-8.
BACKGROUND
Acute kidney injury (AKI) is a frequent form of organ injury in cardiogenic shock. However, data on AKI markers such as plasma proenkephalin (P-PENK) and neutrophil gelatinase-associated lipocalin (P-NGAL) in cardiogenic shock populations are lacking. The objective of this study was to assess the ability of P-PENK and P-NGAL to predict acute kidney injury and mortality in cardiogenic shock.
RESULTS
P-PENK and P-NGAL were measured at different time points between baseline and 48 h in 154 patients from the prospective CardShock study. The outcomes assessed were AKI defined by an increase in creatinine within 48 h and all-cause 90-day mortality. Mean age was 66 years and 26% were women. Baseline levels of P-PENK and P-NGAL (median [interquartile range]) were 99 (71-150) pmol/mL and 138 (84-214) ng/mL. P-PENK > 84.8 pmol/mL and P-NGAL > 104 ng/mL at baseline were identified as optimal cut-offs for AKI prediction and independently associated with AKI (adjusted HRs 2.2 [95% CI 1.1-4.4, p = 0.03] and 2.8 [95% CI 1.2-6.5, p = 0.01], respectively). P-PENK and P-NGAL levels at baseline were also associated with 90-day mortality. For patients with oliguria < 0.5 mL/kg/h for > 6 h before study enrollment, 90-day mortality differed significantly between patients with low and high P-PENK/P-NGAL at baseline (5% vs. 68%, p < 0.001). However, the biomarkers provided best discrimination for mortality when measured at 24 h. Identified cut-offs of P-PENK > 105.7 pmol/L and P-NGAL > 151 ng/mL had unadjusted hazard ratios of 5.6 (95% CI 3.1-10.7, p < 0.001) and 5.2 (95% CI 2.8-9.8, p < 0.001) for 90-day mortality. The association remained significant despite adjustments with AKI and two risk scores for mortality in cardiogenic shock.
CONCLUSIONS
High levels of P-PENK and P-NGAL at baseline were independently associated with AKI in cardiogenic shock patients. Furthermore, oliguria before study inclusion was associated with worse outcomes only if combined with high baseline levels of P-PENK or P-NGAL. High levels of both P-PENK and P-NGAL at 24 h were found to be strong and independent predictors of 90-day mortality.
TRIAL REGISTRATION
NCT01374867 at www.clinicaltrials.gov , registered 16 Jun 2011-retrospectively registered.
背景
急性肾损伤（AKI）是心源性休克中常见的器官损伤形式。然而，关于心源性休克人群中AKI标志物如血浆前脑啡肽原（P-PENK）和中性粒细胞明胶酶相关脂质运载蛋白（P-NGAL）的数据尚缺。本研究的目的是评估P-PENK和P-NGAL预测心源性休克患者急性肾损伤和死亡率的能力。
结果
在前瞻性CardShock研究的154例患者中，于基线至48小时的不同时间点测量了P-PENK和P-NGAL。评估的结局为48小时内肌酐升高定义的AKI和全因90天死亡率。平均年龄为66岁，26%为女性。P-PENK和P-NGAL的基线水平（中位数[四分位间距]）分别为99（71 - 150）pmol/mL和138（84 - 214）ng/mL。基线时P-PENK > 84.8 pmol/mL和P-NGAL > 104 ng/mL被确定为预测AKI的最佳临界值，且与AKI独立相关（校正后风险比分别为2.2[95%CI 1.1 - 4.4，p = 0.03]和2.8[95%CI 1.2 - 6.5，p = 0.01]）。基线时P-PENK和P-NGAL水平也与90天死亡率相关。对于入组前少尿<0.5 mL/kg/h超过6小时的患者，基线时P-PENK/P-NGAL低水平和高水平患者的90天死亡率有显著差异（5%对68%，p < 0.001）。然而，这些生物标志物在24小时测量时对死亡率的区分度最佳。确定的P-PENK > 105.7 pmol/L和P-NGAL > 151 ng/mL的临界值对90天死亡率的未校正风险比分别为5.6（95%CI 3.1 - 10.7，p < 0.001）和5.2（95%CI 2.8 - 9.8，p < 0.001）。尽管对AKI及心源性休克死亡率的两个风险评分进行了校正，该关联仍显著。
结论
基线时高水平的P-PENK和P-NGAL与心源性休克患者的AKI独立相关。此外，入组前少尿仅在与高水平的基线P-PENK或P-NGAL同时存在时才与更差的结局相关。发现24小时时高水平的P-PENK和P-NGAL均是90天死亡率的强有力且独立的预测指标。
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