Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Division of Nephrology, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Int J Mol Sci. 2020 May 15;21(10):3506. doi: 10.3390/ijms21103506.
Kidney transplantation is the preferred treatment for end-stage kidney disease (ESKD). Compared to maintenance dialysis, kidney transplantation results in improved patient survival and quality of life. Kidneys from living donors perform best; however, many patients with ESKD depend on kidneys from deceased donors. After procurement, donor kidneys are placed in a cold-storage solution until a suitable recipient is located. Sadly, prolonged cold storage times are associated with inferior transplant outcomes; therefore, in most situations when considering donor kidneys, long cold-storage times are avoided. The identification of novel mechanisms of cold-storage-related renal damage will lead to the development of new therapeutic strategies for preserving donor kidneys; to date, these mechanisms remain poorly understood. In this review, we discuss the importance of mitochondrial and proteasome function, protein homeostasis, and renal recovery during stress from cold storage plus transplantation. Additionally, we discuss novel targets for therapeutic intervention to improve renal outcomes.
肾移植是治疗终末期肾病（ESKD）的首选方法。与维持性透析相比，肾移植可提高患者的生存率和生活质量。活体供肾的效果最佳；然而，许多 ESKD 患者依赖于已故供者的肾脏。在获取后，供肾被置于冷藏溶液中，直到找到合适的受者。不幸的是，长时间的冷藏与较差的移植结果相关；因此，在大多数情况下，在考虑供肾时，会避免长时间的冷藏。确定与冷藏相关的肾损伤的新机制将导致开发新的治疗策略来保存供肾；迄今为止，这些机制仍知之甚少。在这篇综述中，我们讨论了冷存储加移植应激过程中线粒体和蛋白酶体功能、蛋白质动态平衡和肾脏恢复的重要性。此外，我们还讨论了改善肾脏结局的治疗干预的新靶点。
