Macula densa NOS1 and transplanted renal graft function

致密斑NOS1与移植肾功能

• 批准号: 9973527
• 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/9973527
• 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

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救命手术 疾病尽管移植后的短期器官存活率有了显著提高， 在过去的几十年里，长期结果仍然不满意的生存半衰期， 肾移植术后约10年。此外，器官短缺是一个全球性危机， 通过使用边缘器官刺激了扩大供体库的新方法。 然而，边缘器官的就业有一个显着较高的发生率延迟移植 与标准供体相比，移植物功能和移植物存活率较低。因此有 迫切需要新的战略来改善长期移植结果。 在这个提议中，一个新的假说，即拯救致密斑NOS1的表达， 将测试用碳酸氢盐碱化肾改善移植的移植物结果。 本提案的研究结果将提供一种新的战略， 翻译的意义，可以适用于任何供体或受体在肾脏 移植此外，还将研究其潜在机制和潜在目标。 肾脏碱化以增强供体致密斑NOS 1的表达或 收件人预计将是一个简单而有效的方法，用于扩大 供体库和改善移植物长期存活。