Macula densa NOS1 and transplanted renal graft function

致密斑NOS1与移植肾功能

• 批准号: 10609888
• 负责人: Lei Wang
• 金额: $ 32.89万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-16 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10609888
• 关键词: Bicarbonates; Cardiac Death; Conscious; Data; Deterioration; Employment; End stage renal failure; Exhibits; Feedback; Generations; Glomerular Filtration Rate; Graft Survival; Half-Life; In Vitro; Incidence; Injury to Kidney; Intake; Ischemia; Kidney; Kidney Transplantation; Life; Macula densa; Measurement; Measures; Mediating; Methods; Mus; NOS1 gene; Neurons; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Organ; Organ Donor; Organ Survival; Organ Transplantation; Outcome; Patients; Play; Prevention; Prevention strategy; Procedures; RNA Splicing; Renal function; Reperfusion Injury; Risk Factors; Role; Survival Rate; Testing; Transplantation; Variant; Wild Type Mouse; delayed graft function; experience; experimental study; graft function; hemodynamics; improved; in vitro activity; in vivo; novel; novel strategies; post-transplant; protein purification; response; therapeutic target; translational potential

Kidney transplantation is a life-saving procedure for patients with end-stage kidney disease. Although the short-term organ survival post-transplantation has improved dramatically over the past decades, the long-term outcomes remain unsatisfied with the survival half-lives for transplanted renal grafts still about 10 years. In addition, organ shortage is a global crisis which has stimulated new approaches on expansion of the donor pool by using marginal organs. However, the employment of marginal organs has a significantly higher incidence of delayed graft function and lower graft survival rate compared with standard criteria donors. Therefore, there is an urgent need for new strategies to improve the long-term graft outcomes. In this proposal, a novel hypothesis that rescue macula densa NOS1 expression by renal alkalization with bicarbonate improves transplanted graft outcomes will be tested. The findings of the present proposal will provide a novel strategy with potential translational significance that could be applied to either donors or recipients during kidney transplantation. Additionally, the underlying mechanisms and potential targets will be examined. Renal alkalization to enhance the expression of macula densa NOS1 expression in donors or recipients is anticipated to be a simple and effective method that is used in the expansion of the donor pool and improvement of long-term graft survival.

肾脏移植是终末期肾脏患者的救生程序 疾病。尽管移植后短期器官的生存却显着改善 在过去的几十年中，长期结果对生存的半衰期不满意 移植的肾移植物仍大约10年。此外，器官短缺是一场全球危机 使用边缘器官刺激了扩大供体池的新方法。 但是，边缘器官的使用情况明显更高的延迟移植 与标准标准供体相比，功能和较低的移植物存活率。因此，有 迫切需要新的策略来改善长期移植结果。 在这一提议中，一个新的假设是通过 将测试碳酸氢盐肾脏碱化，改善移植的移植结果。 本提案的发现将提供一种具有潜力的新型策略 肾脏期间可以应用于捐助者或接受者的翻译意义 移植。另外，将检查基本机制和潜在目标。 肾脏碱化以增强捐赠者或 预计接收者将是一种简单有效的方法，用于扩展 供体池和长期移植生存的改善。