Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Division of Nephrology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan.
Crit Care. 2022 Nov 12;26(1):349. doi: 10.1186/s13054-022-04223-6.
Several biomarkers have been proposed to predict the occurrence of acute kidney injury (AKI); however, their efficacy varies between different trials. The aim of this study was to compare the predictive performance of different candidate biomarkers for AKI.
In this systematic review, we searched PubMed, Medline, Embase, and the Cochrane Library for papers published up to August 15, 2022. We selected all studies of adults (> 18 years) that reported the predictive performance of damage biomarkers (neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid-binding protein (L-FABP)), inflammatory biomarker (interleukin-18 (IL-18)), and stress biomarker (tissue inhibitor of metalloproteinases-2 × insulin-like growth factor-binding protein-7 (TIMP-2 × IGFBP-7)) for the occurrence of AKI. We performed pairwise meta-analyses to calculate odds ratios (ORs) and 95% confidence intervals (CIs) individually. Hierarchical summary receiver operating characteristic curves (HSROCs) were used to summarize the pooled test performance, and the Grading of Recommendations, Assessment, Development and Evaluations criteria were used to appraise the quality of evidence.
We identified 242 published relevant studies from 1,803 screened abstracts, of which 110 studies with 38,725 patients were included in this meta-analysis. Urinary NGAL/creatinine (diagnostic odds ratio [DOR] 16.2, 95% CI 10.1-25.9), urinary NGAL (DOR 13.8, 95% CI 10.2-18.8), and serum NGAL (DOR 12.6, 95% CI 9.3-17.3) had the best diagnostic accuracy for the risk of AKI. In subgroup analyses, urinary NGAL, urinary NGAL/creatinine, and serum NGAL had better diagnostic accuracy for AKI than urinary IL-18 in non-critically ill patients. However, all of the biomarkers had similar diagnostic accuracy in critically ill patients. In the setting of medical and non-sepsis patients, urinary NGAL had better predictive performance than urinary IL-18, urinary L-FABP, and urinary TIMP-2 × IGFBP-7: 0.3. In the surgical patients, urinary NGAL/creatinine and urinary KIM-1 had the best diagnostic accuracy. The HSROC values of urinary NGAL/creatinine, urinary NGAL, and serum NGAL were 91.4%, 85.2%, and 84.7%, respectively.
Biomarkers containing NGAL had the best predictive accuracy for the occurrence of AKI, regardless of whether or not the values were adjusted by urinary creatinine, and especially in medically treated patients. However, the predictive performance of urinary NGAL was limited in surgical patients, and urinary NGAL/creatinine seemed to be the most accurate biomarkers in these patients. All of the biomarkers had similar predictive performance in critically ill patients. Trial registration CRD42020207883 , October 06, 2020.
已有多种生物标志物被提出用于预测急性肾损伤(AKI)的发生,但它们在不同试验中的疗效存在差异。本研究旨在比较不同候选生物标志物预测 AKI 的性能。
在这项系统评价中,我们检索了截至 2022 年 8 月 15 日在 PubMed、Medline、Embase 和 Cochrane 图书馆发表的所有论文。我们选择了所有报告损伤生物标志物(中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、肾损伤分子-1(KIM-1)、肝型脂肪酸结合蛋白(L-FABP))、炎症生物标志物(白细胞介素-18(IL-18))和应激生物标志物(金属蛋白酶组织抑制剂-2×胰岛素样生长因子结合蛋白-7(TIMP-2×IGFBP-7))用于预测 AKI 发生的成年人(>18 岁)的研究。我们进行了两两荟萃分析,以单独计算优势比(OR)和 95%置信区间(CI)。分层汇总受试者工作特征曲线(HSROC)用于汇总汇总检验性能,使用推荐、评估、开发和评估标准(GRADE)对证据质量进行评估。
我们从 1803 篇筛选的摘要中确定了 242 篇已发表的相关研究,其中 110 项研究共纳入 38725 名患者纳入本荟萃分析。尿 NGAL/肌酐(诊断优势比 [DOR] 16.2,95%CI 10.1-25.9)、尿 NGAL(DOR 13.8,95%CI 10.2-18.8)和血清 NGAL(DOR 12.6,95%CI 9.3-17.3)对 AKI 风险的诊断准确性最高。在亚组分析中,与非危重病患者中的尿 IL-18 相比,尿 NGAL、尿 NGAL/肌酐和血清 NGAL 对 AKI 具有更好的诊断准确性。然而,所有生物标志物在危重病患者中的诊断准确性相似。在医疗和非脓毒症患者中,尿 NGAL 预测性能优于尿 IL-18、尿 L-FABP 和尿 TIMP-2×IGFBP-7:0.3。在手术患者中,尿 NGAL/肌酐和尿 KIM-1 具有最佳的诊断准确性。尿 NGAL/肌酐、尿 NGAL 和血清 NGAL 的 HSROC 值分别为 91.4%、85.2%和 84.7%。
含有 NGAL 的生物标志物对 AKI 的发生具有最佳的预测准确性,无论其值是否通过尿肌酐进行调整,特别是在接受药物治疗的患者中。然而,尿 NGAL 在手术患者中的预测性能有限,尿 NGAL/肌酐似乎是这些患者中最准确的生物标志物。所有生物标志物在危重病患者中的预测性能相似。试验注册 CRD42020207883,2020 年 10 月 6 日。