Macula densa NOS1 and transplanted renal graft function

致密斑NOS1与移植肾功能

• 批准号: 10380831
• 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/10380831
• 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; Lead; 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; Savings; Survival Rate; Testing; Transplant Recipients; 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; 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.

肾移植是终末期肾病患者的挽救生命的手术 疾病。尽管移植后的短期器官存活率已显着提高 在过去的几十年里，长期结果仍然不满意于生存半衰期 移植肾尚有10年左右的寿命。此外，器官短缺是一场全球性危机 刺激了通过使用边际器官扩大捐助者库的新方法。 然而，边缘器官的使用延迟移植的发生率明显较高 与标准供体相比，功能和移植物存活率较低。因此，有 迫切需要新的策略来改善长期移植结果。 在这个提议中，一个新的假设通过拯救致密斑 NOS1 的表达 将测试用碳酸氢盐碱化肾脏可改善移植物的结果。 本提案的研究结果将提供一种具有潜力的新颖策略 翻译意义可应用于肾脏移植过程中的捐赠者或接受者 移植。此外，还将研究潜在的机制和潜在目标。 碱化肾脏以增强供体或致密斑 NOS1 的表达 预计接收者将是一种简单有效的方法，可用于扩展 供体库和长期移植物存活的改善。