Renal Delivery of Pharmacologic Agents During Machine Perfusion to Prevent Ischaemia-Reperfusion Injury: From Murine Model to Clinical Trials.
Renal Delivery of Pharmacologic Agents During Machine Perfusion to Prevent Ischaemia-Reperfusion Injury: From Murine Model to Clinical Trials.
复制标题
DOI：
10.3389/fimmu.2021.673562
复制
发表时间：
2021
影响因子：
7.3
通讯作者：
Gesualdo L
中科院分区：
文献类型：
--
作者：
Franzin R;Stasi A;Fiorentino M;Simone S;Oberbauer R;Castellano G;Gesualdo L
供体器官短缺仍然是等待名单患者获得肾移植的严重障碍，肾移植是终末期肾病（ESKD）的最佳治疗方法。为了扩大移植数量，使用来自老年ECD或DCD供体的低质量器官已成为既定的常规，但代价是原发性无功能、移植物功能延迟和移植物长期存活率较低的发生率增加。在过去的几年里，在肾移植领域已经取得了一些进展，从外科手术到保存策略。为了改善肾脏结局，研究重点是开发创新和动态保存技术，以评估移植物功能并在移植前通过药物干预促进再生。这篇综述概述了目前的知识，这些新的保存策略的机器灌注和药理学干预在不同的时间可能性：在器官供体，离体灌注机修复过程中或在收件人实施后。我们将报告作为抗氧化剂和抗炎剂，senolytics剂，补体抑制剂，HDL，siRNA和H2S补充剂的治疗。在保存状态期间药物的肾脏递送提供了以隔离方式治疗器官的机会窗口和关键的给药途径。即使离体给药后移植的研究报道很少，靶向与肾衰竭相关的生物学途径（即氧化应激、补体系统、纤维化）可能是一种有前途的治疗策略，可改善各种供体器官的质量并扩大器官可用性。
Donor organ shortage still remains a serious obstacle for the access of wait-list patients to kidney transplantation, the best treatment for End-Stage Kidney Disease (ESKD). To expand the number of transplants, the use of lower quality organs from older ECD or DCD donors has become an established routine but at the price of increased incidence of Primary Non-Function, Delay Graft Function and lower-long term graft survival. In the last years, several improvements have been made in the field of renal transplantation from surgical procedure to preservation strategies. To improve renal outcomes, research has focused on development of innovative and dynamic preservation techniques, in order to assess graft function and promote regeneration by pharmacological intervention before transplantation. This review provides an overview of the current knowledge of these new preservation strategies by machine perfusions and pharmacological interventions at different timing possibilities: in the organ donor, ex-vivo during perfusion machine reconditioning or after implementation in the recipient. We will report therapies as anti-oxidant and anti-inflammatory agents, senolytics agents, complement inhibitors, HDL, siRNA and H2S supplementation. Renal delivery of pharmacologic agents during preservation state provides a window of opportunity to treat the organ in an isolated manner and a crucial route of administration. Even if few studies have been reported of transplantation after ex-vivo drugs administration, targeting the biological pathway associated to kidney failure (i.e. oxidative stress, complement system, fibrosis) might be a promising therapeutic strategy to improve the quality of various donor organs and expand organ availability.
登录
查看更多内容
影响因子：
6.2
作者：
Brasile, L;Stubenitsky, BM;Kootstra, G
通讯作者：
Kootstra, G
裸 caspase-3 siRNA 保存的无保护猪自体移植肾中涉及的先天免疫激活
影响因子：
7.4
作者：
Yang C;Li L;Xue Y;Zhao Z;Zhao T;Jia Y;Rong R;Xu M;Nicholson ML;Zhu T;Yang B
通讯作者：
Yang B
影响因子：
3.9
作者：
Bang, Ji-Yeon;Kim, Sae-Gyeol;Song, Jun-Gol
通讯作者：
Song, Jun-Gol
影响因子：
9.6
作者：
Bagul, A.;Hosgood, S. A.;Nicholson, M. L.
通讯作者：
Nicholson, M. L.
影响因子：
6.2
作者：
Damman, Jeffrey;Bloks, Vincent W.;Seelen, Marc A.
通讯作者：
Seelen, Marc A.