Derivation and validation of urinary TIMP-1 for the prediction of acute kidney injury and mortality in critically ill children.
Derivation and validation of urinary TIMP-1 for the prediction of acute kidney injury and mortality in critically ill children.
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DOI：
10.1186/s12967-022-03302-0
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发表时间：
2022-02-23
影响因子：
7.4
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Huang H;Lin Q;Dai X;Chen J;Bai Z;Li X;Fang F;Li Y
急性肾损伤（阿基）与高发病率和死亡率相关。已确定多种尿液生物标志物与阿基和结局的预测相关。然而，这些尿液生物标志物对于阿基和相关结果的准确性尚未明确定义，特别是在异质性人群中。该研究的目的是比较10种现有或潜在的尿液生物标志物预测阿基和儿科重症监护病房（PICU）死亡率的能力，并验证尿金属蛋白酶组织抑制剂-1（uTIMP-1）作为早期预测异质性危重病儿童的更好生物标志物。设计了一种具有单独危重队列的推导-验证方法。我们首先进行了一项前瞻性队列研究，以确定123名儿童在PICU住院的前7天内连续测量的10种尿生物标志物预测阿基和PICU死亡率的能力（推导研究），并在357名重症儿童的单独队列中进一步验证了uTIMP-1的更好生物标志物（验证研究）。阿基诊断基于血清肌酐和尿量的KDIGO分类。PICU死亡率定义为全因死亡。在推导队列中，123名儿童中有17名（13.8%）在PICU住院期间发生阿基3期或死亡，初始和峰值uTIMP-1分别显示预测阿基3期或死亡的最高AUC为0.87（0.79-0.94）和0.90（0.84-0.96）。在验证队列中，78/357（21.8%）在入院后第一周内发生阿基，38（10.6%）在PICU住院期间死亡。初始uTIMP-1水平被证实与阿基独立相关（AOR = 2.88，95% CI 1.97-4.21），重度阿基（AOR = 2.62，95% CI 1.78-3.88）、阿基3期（AOR = 2.94，95% CI 1.84-4.68）和PICU死亡率（AOR = 1.92，95% CI 1.11-3.30）。uTIMP-1对阿基、重度阿基、阿基3期和PICU死亡率的预测值分别为0.80（0.74-0.86）、0.83（0.77-0.89）、0.84（0.77-0.92）和0.83（0.76-0.89）。在独立的前瞻性队列中，尿TIMP-1水平已被确定并验证为与阿基和PICU死亡率独立相关，并且可能是危重儿童阿基和PICU死亡率的早期潜在指标。在线版本包含补充材料，可通过10.1186/s12967-022-03302-0获得。
Acute kidney injury (AKI) is associated with high morbidity and mortality. Multiple urinary biomarkers have been identified to be associated with the prediction of AKI and outcomes. However, the accuracy of these urinary biomarkers for AKI and associated outcomes has not been clearly defined, especially in heterogeneous populations. The aims of the study were to compare the ability of 10 existing or potential urinary biomarkers to predict AKI and pediatric intensive care unit (PICU) mortality and validate urinary tissue inhibitor of metalloproteinases-1 (uTIMP-1) as a better biomarker for early prediction in heterogeneous critically ill children. A derivation-validation approach with separate critically ill cohorts was designed. We first conducted a prospective cohort study to determine the ability of 10 urinary biomarkers serially measured in 123 children during the first 7 days of PICU stay to predict AKI and PICU mortality (derivation study) and further validated the better biomarker of uTIMP-1 in a separate cohort of 357 critically ill children (validation study). AKI diagnosis was based on KDIGO classification with serum creatinine and urine output. PICU mortality was defined as all-cause mortality. In the derivation cohort, 17 of 123 (13.8%) children developed AKI stage 3 or died during the PICU stay, and both the initial and peak uTIMP-1 displayed the highest AUCs of 0.87 (0.79–0.94) and 0.90 (0.84–0.96), respectively, for predicting AKI stage 3 or death. In the validation cohort, 78 of 357 (21.8%) developed AKI during the first week after admission, and 38 (10.6%) died during the PICU stay. The initial uTIMP-1 level was validated to be independently associated with AKI (AOR = 2.88, 95% CI 1.97–4.21), severe AKI (AOR = 2.62, 95% CI 1.78–3.88), AKI stage 3 (AOR = 2.94, 95% CI 1.84–4.68) and PICU mortality (AOR = 1.92, 95% CI 1.11–3.30) after adjustment for potential confounders. The predictive values of uTIMP-1 for AKI, severe AKI, AKI stage 3 and PICU mortality were 0.80 (0.74–0.86), 0.83 (0.77–0.89), 0.84 (0.77–0.92) and 0.83 (0.76–0.89), respectively. Urinary TIMP-1 levels have been identified and validated to be independently associated with AKI and PICU mortality in independent prospective cohorts and may be an early potential indicator of AKI and PICU mortality in critically ill children. The online version contains supplementary material available at 10.1186/s12967-022-03302-0.
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DOI：
10.1056/nejmoa1611391
发表时间：
2017-01-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Kaddourah A;Basu RK;Bagshaw SM;Goldstein SL;AWARE Investigators
通讯作者：
AWARE Investigators
影响因子：
3.6
作者：
Kuai, Yuxian;Huang, Hui;Li, Yanhong
通讯作者：
Li, Yanhong
影响因子：
4.3
作者：
Erez, Daniella Levy;Denburg, Michelle R.;Sullivan, Kathleen E.
通讯作者：
Sullivan, Kathleen E.
DOI：
10.1080/15287394.2017.1299655
发表时间：
2017-01-01
影响因子：
2.6
作者：
Kim, Kyeong Seok;Yang, Hun Yong;Kim, Hyung Sik
通讯作者：
Kim, Hyung Sik
影响因子：
6.7
作者：
George B;Wen X;Mercke N;Gomez M;O'Bryant C;Bowles DW;Hu Y;Hogan SL;Joy MS;Aleksunes LM
通讯作者：
Aleksunes LM