Renal, Vascular and Diabetes Research Laboratory, IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, 28040 Madrid, Spain.
Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Hospital Universitario Reina Sofía, 14004 Córdoba, Spain.
Int J Mol Sci. 2021 Jan 15;22(2):816. doi: 10.3390/ijms22020816.
Acute kidney injury (AKI) is an important health problem, affecting 13.3 million individuals/year. It is associated with increased mortality, mainly in low- and middle-income countries, where renal replacement therapy is limited. Moreover, survivors show adverse long-term outcomes, including increased risk of developing recurrent AKI bouts, cardiovascular events, and chronic kidney disease. However, there are no specific treatments to decrease the adverse consequences of AKI. Epidemiological and preclinical studies show the pathological role of inflammation in AKI, not only at the acute phase but also in the progression to chronic kidney disease. Toll-like receptors (TLRs) are key regulators of the inflammatory response and have been associated to many cellular processes activated during AKI. For that reason, a number of anti-inflammatory agents targeting TLRs have been analyzed in preclinical studies to decrease renal damage during AKI. In this review, we updated recent knowledge about the role of TLRs, mainly TLR4, in the initiation and development of AKI as well as novel compounds targeting these molecules to diminish kidney injury associated to this pathological condition.
急性肾损伤(AKI)是一个重要的健康问题,每年影响 1330 万人。它与死亡率的增加有关,主要发生在中低收入国家,这些国家的肾脏替代疗法有限。此外,幸存者表现出不良的长期预后,包括发展为复发性 AKI 发作、心血管事件和慢性肾脏病的风险增加。然而,目前还没有专门的治疗方法来减少 AKI 的不良后果。流行病学和临床前研究表明炎症在 AKI 中的病理作用,不仅在急性期,而且在向慢性肾脏病的进展中。Toll 样受体(TLRs)是炎症反应的关键调节剂,与 AKI 期间激活的许多细胞过程有关。出于这个原因,许多针对 TLRs 的抗炎药物已在临床前研究中进行了分析,以减少 AKI 期间的肾脏损伤。在这篇综述中,我们更新了关于 TLRs(主要是 TLR4)在 AKI 的发生和发展中的作用以及针对这些分子的新型化合物的最新知识,这些化合物可减少与该病理状况相关的肾脏损伤。