Faucher Quentin, Alarcan Hugo, Marquet Pierre, Barin-Le Guellec Chantal
IPPRITT UMR1248, Université de Limoges, INSERM, F-87042 Limoges, France.
Department of Pharmacology and Toxicology, CHU Limoges, F-87042 Limoges, France.
J Clin Med. 2020 Aug 12;9(8):2610. doi: 10.3390/jcm9082610.
Ischemia-reperfusion (IR)-induced acute kidney injury (IRI) is an inevitable event in kidney transplantation. It is a complex pathophysiological process associated with numerous structural and metabolic changes that have a profound influence on the early and the late function of the transplanted kidney. Proximal tubular cells are particularly sensitive to IRI. These cells are involved in renal and whole-body homeostasis, detoxification processes and drugs elimination by a transporter-dependent, transcellular transport system involving Solute Carriers (SLCs) and ATP Binding Cassettes (ABCs) transporters. Numerous studies conducted mainly in animal models suggested that IRI causes decreased expression and activity of some major tubular transporters. This could favor uremic toxins accumulation and renal metabolic alterations or impact the pharmacokinetic/toxicity of drugs used in transplantation. It is of particular importance to understand the underlying mechanisms and effects of IR on tubular transporters in order to improve the mechanistic understanding of IRI pathophysiology, identify biomarkers of graft function or promote the design and development of novel and effective therapies. Modulation of transporters' activity could thus be a new therapeutic opportunity to attenuate kidney injury during IR.
缺血再灌注（IR）诱导的急性肾损伤（IRI）是肾移植中不可避免的事件。它是一个复杂的病理生理过程，与众多结构和代谢变化相关，这些变化对移植肾的早期和晚期功能有深远影响。近端肾小管细胞对IRI特别敏感。这些细胞通过涉及溶质载体（SLCs）和ATP结合盒（ABCs）转运蛋白的依赖转运体的跨细胞转运系统参与肾脏和全身的稳态、解毒过程及药物清除。主要在动物模型中进行的大量研究表明，IRI会导致一些主要肾小管转运蛋白的表达和活性降低。这可能有利于尿毒症毒素的积累和肾脏代谢改变，或影响移植中使用药物的药代动力学/毒性。了解IR对肾小管转运蛋白的潜在机制和影响对于增进对IRI病理生理学的机制理解、识别移植肾功能的生物标志物或促进新型有效疗法的设计和开发尤为重要。因此，调节转运蛋白的活性可能是减轻IR期间肾损伤的一个新的治疗机会。
