Devarajan Prasad
Department of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, United States.
Front Pediatr. 2020 Mar 17;8:70. doi: 10.3389/fped.2020.00070. eCollection 2020.
Decades of pre-clinical research have revealed biologic pathways that have suggested potential therapies for acute kidney injury (AKI) in experimental models. However, translating these to human AKI has largely yielded disappointing results. Fortunately, recent discoveries in AKI molecular mechanisms are providing new opportunities for early detection and novel interventions. This review identifies technologies that are revealing the exceptionally complex nature of the normal kidney, the remarkable heterogeneity of the AKI syndrome, and the myriad responses of the kidney to AKI. Based on the current state of the art, novel approaches to improve the bench-to-bedside translation of novel discoveries are proposed. These strategies include the use of unbiased approaches to improve our understanding of human AKI, establishment of irrefutable biologic plausibility for proposed biomarkers and therapies, identification of patients at risk for AKI pre-injury using clinical scores and non-invasive biomarkers, initiation of safe, and effective preventive interventions of pre-injury in susceptible patients, identification of patients who may develop AKI post-injury using electronic triggers, clinical scores, and novel biomarkers, employment of sequential biomarkers to initiate appropriate therapies based on knowledge of the underlying pathophysiology, use of new biomarkers as criteria for enrollment in randomized clinical trials, assessing efficacy, and empowering the drug development process, and early initiation of anti-fibrotic therapies. These strategies are immediately actionable and hold tremendous promise for effective bench-to-bedside translation of novel discoveries that will change the current dismal prognosis of human AKI.
数十年的临床前研究揭示了一些生物学途径，这些途径在实验模型中提示了急性肾损伤（AKI）的潜在治疗方法。然而，将这些方法转化应用于人类AKI，大多产生了令人失望的结果。幸运的是，最近在AKI分子机制方面的发现为早期检测和新型干预措施提供了新机会。本综述确定了一些技术，这些技术揭示了正常肾脏异常复杂的本质、AKI综合征显著的异质性以及肾脏对AKI的多种反应。基于当前的技术水平，提出了改进新发现从实验室到临床转化的新方法。这些策略包括使用无偏倚方法来增进我们对人类AKI的理解，为所提出的生物标志物和治疗方法建立无可辩驳的生物学合理性，利用临床评分和非侵入性生物标志物识别损伤前有AKI风险的患者，对易感患者在损伤前启动安全有效的预防性干预措施，利用电子触发因素、临床评分和新型生物标志物识别损伤后可能发生AKI的患者，根据对潜在病理生理学的了解，采用序贯生物标志物来启动适当的治疗，将新的生物标志物用作随机临床试验入组标准、评估疗效并推动药物研发进程，以及尽早启动抗纤维化治疗。这些策略可立即付诸行动，对于有效实现新发现从实验室到临床的转化具有巨大潜力，这将改变目前人类AKI令人沮丧的预后。
