Persistent acute kidney injury biomarkers: A systematic review and meta-analysis

IF 3.2 3区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY
Keran Shi , Wei Jiang , Lin Song , Xianghui Li , Chuanqing Zhang, Luanluan Li, Yunfan Feng, Jiayan Yang, Tianwei Wang, Haoran Wang, Lulu Zhou, Jiangquan Yu, Ruiqiang Zheng
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引用次数: 0

Abstract

Background

Various biomarkers reportedly predict persistent acute kidney injury (AKI) despite their varying predictive performance across clinical trials. This study aims to compare the accuracy of various biomarkers in predicting persistent AKI in different populations and regions.

Methods

In this meta-analysis, we searched for urinary C–C motif chemokine ligand 14 (CCL14), Tissue inhibitor of metalloproteinase-2&insulin-like growth factor-binding protein-7 (TIMP-2&IGFBP7), Neutrophil Gelatinase-Associated Lipocalin (NGAL), plasma Cystatin C (pCysC), Soluble urokinase plasminogen activator receptor (suPAR), Proenkephalin (PenK) and urinary dickkopf-3:urinary creatinine (uDKK3:uCr) from various databases including Medline, PubMed, Embase, and Cochrane. This was geared towards predicting persistent AKI in adults (>18 years). Hierarchically summarized subject work characteristic curves (HSROC) and diagnostic odds ratio (DOR) values were used to summarize the diagnostic accuracy of the biomarkers. Further, meta-regression and subgroup analyses were carried out to identify sources of heterogeneity as well as evaluate the best predictive biomarkers in different populations and regions.

Results

We screened 31 studies from 2,356 studies and assessed the diagnostic value of 7 biomarkers for persistent AKI. Overall, CCL14 had the best diagnostic efficacy with an AUC of 0.79 (95 % CI 0.75–0.82), whereas TIMP-2 & IGFBP7, NGAL, and pCysC had diagnostic efficacy of 0.75 (95 % CI 0.71–0.79),0.71 (95 % CI 0.67–0.75), and 0.7007, respectively. Due to a limited number of studies, PenK, uDKK3:uCr, and suPAR were not subjected to meta-analysis; however, relevant literature reported diagnostic efficacy above 0.70. Subgroup analyses based on population, region, biomarker detection time, AKI onset time, and AKI duration revealed that in the intensive care unit (ICU) population, the AUC of CCL14 was 0.8070, the AUC of TIMP-2 & IGFBP7 was 0.726, the AUC of pCysC was 0.72, and the AUC of NGAL was 0.7344; in the sepsis population, the AUC of CCL14 was 0.85, the AUC of TIMP-2&IGFBP7 was 0.7438, and the AUC of NGAL was 0.544; in the post-operative population, the AUC of CCL14 was 0.83–0.93, the AUC of TIMP-2&IGFBP7 was 0.71, and the AUC of pCysC was 0.683. Regional differences were observed in biomarker prediction of persistent kidney injury, with AUCs of 0.8558 for CCL14, 0.7563 for TIMP-2 & IGFBP7, and 0.7116 for NGAL in the Eurasian American population. In the sub-African population, TIMP-2 & IGFBP7 had AUCs of 0.7945, 0.7418 for CCL14, 0.7097 for NGAL, and 0.7007 for pCysC. for TIMP-2 & IGFBP7 was 0.7945, AUC for CCL14 was 0.7418, AUC for NGAL was 0.7097, and AUC for pCysC was 0.7007 in the sub-African population. Duration of biomarker detection, AKI onset, and AKI did not influence the optimal predictive performance of CCL14. Subgroup analysis and meta-regression of CCL14-related studies revealed that CCL14 is the most appropriate biomarker for predicting persistent stage 2–3 AKI, with heterogeneity stemming from sample size and AKI staging.

Conclusion

This meta-analysis discovered CCL14 as the best biomarker to predict persistent AKI, specifically persistent stage 2–3 AKI.

持续性急性肾损伤生物标志物:系统综述与荟萃分析。
背景:据报道,各种生物标志物可预测持续性急性肾损伤(AKI),尽管它们在临床试验中的预测性能各不相同。本研究旨在比较各种生物标志物在不同人群和地区预测持续性 AKI 的准确性:在这项荟萃分析中,我们搜索了尿液中的 C-C mot chemokine ligand 14 (CCL14)、组织金属蛋白酶抑制剂-2&胰岛素样生长因子结合蛋白-7 (TIMP-2&IGFBP7)、中性粒细胞明胶酶 (Neutrophil Gelatinasease) 和胰岛素样生长因子结合蛋白-7 (TIMP-2&IGFBP7)、中性粒细胞明胶酶相关脂联素(NGAL)、血浆胱抑素 C(pCysC)、可溶性尿激酶纤溶酶原激活物受体(suPAR)、前脑啡肽(PenK)和尿液中的 dickkopf-3:这些数据来自各种数据库,包括 Medline、PubMed、Embase 和 Cochrane。其目的是预测成人(18 岁以上)的持续性 AKI。分层总结的受试者工作特征曲线(HSROC)和诊断几率比(DOR)值用于总结生物标志物的诊断准确性。此外,我们还进行了元回归和亚组分析,以确定异质性的来源,并评估不同人群和地区的最佳预测生物标志物:我们从 2356 项研究中筛选出 31 项研究,评估了 7 种生物标志物对持续性 AKI 的诊断价值。总体而言,CCL14 的诊断效果最好,其 AUC 为 0.79(95% CI 0.75-0.82),而 TIMP-2 & IGFBP7、NGAL 和 pCysC 的诊断效果分别为 0.75(95% CI 0.71-0.79)、0.71(95% CI 0.67-0.75)和 0.7007。由于研究数量有限,PenK、uDKK3:uCr 和 suPAR 没有进行荟萃分析;但是,相关文献报告的诊断效果高于 0.70。基于人群、地区、生物标记物检测时间、AKI 发病时间和 AKI 持续时间的亚组分析显示,在重症监护室(ICU)人群中,CCL14 的 AUC 为 0.8070,TIMP-2 & IGFBP7 的 AUC 为 0.726,pCysC 的 AUC 为 0.72,NGAL 的 AUC 为 0.7344;在败血症人群中,CCL14 的 AUC 为 0.85,TIMP-2&IGFBP7 的 AUC 为 0.7438,NGAL 的 AUC 为 0.544;在术后人群中,CCL14 的 AUC 为 0.83-0.93,TIMP-2&IGFBP7 的 AUC 为 0.71,pCysC 的 AUC 为 0.683。在持续性肾损伤的生物标志物预测方面观察到了地区差异,在欧亚美洲人群中,CCL14 的 AUC 为 0.8558,TIMP-2 & IGFBP7 为 0.7563,NGAL 为 0.7116。在亚非人群中,TIMP-2 和 IGFBP7 的 AUC 为 0.7945,CCL14 为 0.7418,NGAL 为 0.7097,pCysC 为 0.7007。生物标记物检测时间、AKI 发病时间和 AKI 均不影响 CCL14 的最佳预测性能。CCL14相关研究的分组分析和元回归显示,CCL14是预测持续性2-3期AKI最合适的生物标记物,异质性源于样本大小和AKI分期:这项荟萃分析发现 CCL14 是预测持续性 AKI(尤其是持续性 2-3 期 AKI)的最佳生物标志物。
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来源期刊
Clinica Chimica Acta
Clinica Chimica Acta 医学-医学实验技术
CiteScore
10.10
自引率
2.00%
发文量
1268
审稿时长
23 days
期刊介绍: The Official Journal of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Clinica Chimica Acta is a high-quality journal which publishes original Research Communications in the field of clinical chemistry and laboratory medicine, defined as the diagnostic application of chemistry, biochemistry, immunochemistry, biochemical aspects of hematology, toxicology, and molecular biology to the study of human disease in body fluids and cells. The objective of the journal is to publish novel information leading to a better understanding of biological mechanisms of human diseases, their prevention, diagnosis, and patient management. Reports of an applied clinical character are also welcome. Papers concerned with normal metabolic processes or with constituents of normal cells or body fluids, such as reports of experimental or clinical studies in animals, are only considered when they are clearly and directly relevant to human disease. Evaluation of commercial products have a low priority for publication, unless they are novel or represent a technological breakthrough. Studies dealing with effects of drugs and natural products and studies dealing with the redox status in various diseases are not within the journal''s scope. Development and evaluation of novel analytical methodologies where applicable to diagnostic clinical chemistry and laboratory medicine, including point-of-care testing, and topics on laboratory management and informatics will also be considered. Studies focused on emerging diagnostic technologies and (big) data analysis procedures including digitalization, mobile Health, and artificial Intelligence applied to Laboratory Medicine are also of interest.
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