University of Pittsburgh, School of Pharmacy, Pittsburgh, PA, USA.
Massachusetts College of Pharmacy and Health Sciences, Boston, MA, USA.
Drug Saf. 2022 Aug;45(8):839-852. doi: 10.1007/s40264-022-01202-2. Epub 2022 Jul 13.
Acute kidney injury (AKI) resulting from nephrotoxic medication use is prominent in hospitalized patients and is attributable to overall increases in mortality and costs of care. Serum creatinine (SCr), the current standard for identifying drug-induced AKI (DIAKI) is often delayed in its response to kidney insult by 26-36 h.
This systematic review seeks to evaluate the clinical utility of several novel kidney damage and stress biomarkers for the prediction/timely detection of DIAKI, in comparison with traditional methods.
A systematic review of the CINAHL, Cochrane Library, Embase, and PubMed databases was conducted per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, for articles analyzing the use of β2-microglobulin (B2M), interleukin (IL)-18, kidney injury molecule-1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL), and tissue inhibitor of metalloproteinase-2 * insulin-like growth factor-binding protein 7 [TIMP-1]*[IGFBP-7], for identifying DIAKI. Primary outcomes included time to DIAKI diagnosis using traditional methods and the time to significant difference in biomarker concentrations between DIAKI and non-AKI study subjects. Secondary outcomes included biomarker concentrations at the time of significant difference between the AKI status groups.
Fifteen unique articles were identified from the literature search. Twelve studies consisted of strictly hospitalized patient populations and three studies included hospitalized patients and patients discharged to home treatment. No studies reported values for urine volume output. Seventy-three percent of studies reported earlier times to significant difference of novel biomarker concentrations between the AKI and non-AKI groups than diagnosis of DIAKI by SCr alone. Significant variation was observed for individual urine biomarker concentrations at time of significant difference between the AKI status groups.
All analyzed biomarkers showed potential for use as early clinical markers of DIAKI, however further consensus on threshold urine concentrations for DIAKI is needed for meaningful implementation of these biomarkers in clinical practice.
肾毒性药物使用导致的急性肾损伤（AKI）在住院患者中较为突出，可导致死亡率和医疗费用增加。血清肌酐（SCr）是目前用于识别药物诱导的 AKI（DIAKI）的标准，但它对肾脏损伤的反应通常会延迟 26-36 小时。
本系统评价旨在评估几种新型肾脏损伤和应激生物标志物在预测/早期检测 DIAKI 方面的临床应用价值，与传统方法相比。
根据 2020 年系统评价和荟萃分析的首选报告项目（PRISMA）指南，对 CINAHL、Cochrane 图书馆、Embase 和 PubMed 数据库进行了系统评价，以分析β2-微球蛋白（B2M）、白细胞介素（IL）-18、肾损伤分子-1（KIM-1）、肝型脂肪酸结合蛋白（L-FABP）、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）和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-1][IGFBP-7]用于识别 DIAKI 的文章。主要结局包括使用传统方法诊断 DIAKI 的时间和 DIAKI 与非 AKI 研究对象之间生物标志物浓度显著差异的时间。次要结局包括 AKI 状态组之间存在显著差异时的生物标志物浓度。
从文献检索中确定了 15 篇独特的文章。12 项研究仅包括住院患者人群，3 项研究包括住院患者和出院至家庭治疗的患者。没有研究报告尿量值。73%的研究报告了新型生物标志物浓度在 AKI 和非 AKI 组之间存在显著差异的时间早于单独使用 SCr 诊断 DIAKI 的时间。在 AKI 状态组之间存在显著差异时，观察到个体尿液生物标志物浓度存在显著差异。
所有分析的生物标志物都显示出作为 DIAKI 早期临床标志物的潜力，但是需要进一步就 DIAKI 的尿液生物标志物浓度阈值达成共识，以便在临床实践中更有意义地实施这些标志物。
