Delrue Charlotte, Speeckaert Marijn M
Department of Nephrology, Ghent University Hospital, 9000 Ghent, Belgium.
Research Foundation-Flanders (FWO), 1000 Brussels, Belgium.
Diagnostics (Basel). 2024 Jun 25;14(13):1350. doi: 10.3390/diagnostics14131350.
Acute kidney damage (AKI) is a serious and common consequence among critically unwell individuals. Traditional biomarkers, such as serum creatinine, frequently fail to detect AKI in its early stages, necessitating the development of new accurate early biomarkers. Tissue inhibitor of metalloproteinases 2 (TIMP-2) has emerged as a promising biomarker for predicting early AKI. The present narrative review investigates the role of TIMP-2 in AKI prediction in a variety of clinical scenarios. In the NephroCheck test, TIMP-2 exceeds established biomarkers for the early identification of AKI in terms of sensitivity and specificity when combined with insulin-like growth factor-binding protein 7 (IGFBP-7). Elevated levels of these biomarkers can provide a warning signal for AKI two to three days before clinical symptoms appear. TIMP-2 and IGFBP-7 have high predictive values, with an area under the curve (AUC) typically above 0.8, indicating good predictive capacity. For example, the [TIMP-2] × [IGFBP-7] product produced an AUC of 0.85 in surgical patients at high risk. In critically ill patients, a threshold of 0.3 (ng/mL)/1000 demonstrated 92% sensitivity and 72% specificity. Elevated TIMP-2 levels have been correlated with higher mortality rates and the need for renal replacement therapy (RRT). In sepsis-associated AKI (SA-AKI), TIMP-2 levels combined with clinical prognostic models improved predictive accuracy (AUC: 0.822). Furthermore, elevated urine TIMP-2 levels were good predictors of AKI in pediatric patients after cardiac surgery, with AUC-ROC values of up to 0.848. Urine output and the presence of concomitant disorders may influence the prognostic accuracy of these biomarkers; therefore, more research is needed to fully understand their utility. The predictive value of TIMP-2 could be strengthened by combining it with other clinical parameters, reinforcing its role in the early detection and treatment of AKI.
急性肾损伤（AKI）是危重症患者中一种严重且常见的后果。传统生物标志物，如血清肌酐，在AKI早期往往无法检测到，因此需要开发新的准确早期生物标志物。金属蛋白酶组织抑制剂2（TIMP - 2）已成为预测早期AKI的一种有前景的生物标志物。本叙述性综述探讨了TIMP - 2在各种临床情况下对AKI预测的作用。在NephroCheck测试中，TIMP - 2与胰岛素样生长因子结合蛋白7（IGFBP - 7）联合使用时，在早期识别AKI方面，其敏感性和特异性超过了已有的生物标志物。这些生物标志物水平升高可在临床症状出现前两到三天为AKI提供预警信号。TIMP - 2和IGFBP - 7具有较高的预测价值，曲线下面积（AUC）通常高于0.8，表明具有良好的预测能力。例如，[TIMP - 2]×[IGFBP - 7]乘积在高危手术患者中的AUC为0.85。在危重症患者中，阈值为0.3（ng/mL）/1000时，敏感性为92%，特异性为72%。TIMP - 2水平升高与较高的死亡率和肾脏替代治疗（RRT）需求相关。在脓毒症相关的AKI（SA - AKI）中，TIMP - 2水平与临床预后模型相结合提高了预测准确性（AUC：0.822）。此外，心脏手术后儿科患者尿TIMP - 2水平升高是AKI的良好预测指标，AUC - ROC值高达0.848。尿量和伴随疾病的存在可能会影响这些生物标志物的预后准确性；因此，需要更多研究来充分了解它们的效用。将TIMP - 2与其他临床参数结合可增强其预测价值，强化其在AKI早期检测和治疗中的作用。
