Department of Surgery, Austin Health, The University of Melbourne, Studley Rd., Heidelberg, VIC, 3084, Australia.
Department of Urology, Austin Health, Heidelberg, VIC, Australia.
J Nephrol. 2019 Aug;32(4):539-547. doi: 10.1007/s40620-019-00582-6. Epub 2019 Jan 11.
Acute kidney injury (AKI) as a result of ischaemia-reperfusion represents a major healthcare burden worldwide. Mortality rates from AKI in hospitalized patients are extremely high and have changed little despite decades of research and medical advances. In 1986, Murry et al. demonstrated for the first time the phenomenon of ischaemic preconditioning to protect against ischaemia-reperfusion injury (IRI). This seminal finding paved the way for a broad body of research, which attempted to understand and ultimately harness this phenomenon for human application. The ability of preconditioning to limit renal IRI has now been demonstrated in multiple different animal models. However, more than 30 years later, a safe and consistent method of protecting human organs, including the kidneys, against IRI is still not available. This review highlights agents which, despite strong preclinical data, have recently failed to reduce AKI in human trials. The multiple reasons which may have contributed to the failure to translate some of the promising findings to clinical therapies are discussed. Agents which hold promise in the clinic because of their recent efficacy in preclinical large animal models are also reviewed.
缺血再灌注引起的急性肾损伤（AKI）是全球范围内的一个主要医疗保健负担。住院患者的 AKI 死亡率极高，尽管经过几十年的研究和医学进步，这一数字几乎没有变化。1986 年，Murry 等人首次证明了缺血预处理现象可预防缺血再灌注损伤（IRI）。这一开创性的发现为广泛的研究铺平了道路，这些研究试图理解并最终将这一现象应用于人类。预处理限制肾 IRI 的能力现已在多种不同的动物模型中得到证实。然而，30 多年后，一种安全且一致的方法来保护人体器官（包括肾脏）免受 IRI 仍然不可用。这篇综述强调了一些药物，尽管有强有力的临床前数据，但最近在人类试验中未能减少 AKI。讨论了导致一些有前途的发现未能转化为临床治疗的多种原因。还回顾了一些在临床上有希望的药物，因为它们最近在临床前大型动物模型中显示出了疗效。
