Donor Kidney Gene Expression and Delayed Graft Function

供体肾基因表达和移植物功能延迟

• 批准号: 6562360
• 负责人: TIMOTHY W MEYER
• 金额: $ 15.88万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-01 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6562360
• 关键词: biopsy; clinical research; gene expression; human subject; kidney function; kidney transplantation; microarray technology; patient oriented research; postmortem; tissue donors; transplantation immunology

DESCRIPTION (provided by applicant): Function of cadaver kidneys over the first few days after transplantation ranges from near zero to normal. Most of the kidneys which exhibit poor initial function eventually recover adequate function. Delayed function, however, has important adverse consequences. It prolongs hospitalization and complicates immunosuppressive therapy. In addition, when defined by a requirement for dialysis during the first week after transplantation, delayed function is one of the major correlates of poor graft survival. The aim of the current proposal is to identify specific changes in cadaver donor kidneys which contribute to delayed graft function. At present, the nature of these changes is largely unknown. The proposed studies will employ microarray technology to profile gene expression in donor kidney biopsies obtained prior to implantation. Recently developed statistical techniques will be used to identify genes whose expression in the donor kidney is most closely associated with poor function over the first few days after implantation. Profiling of gene expression by microarray analysis provides a screening mechanism of unmatched power. Because of the availability of wedge biopsies, this method can be more easily applied to the study of donor kidney injury than to any other problem in clinical nephrology. Identification of genes whose expression in cadaver kidneys is associated with poor graft function would facilitate further study of the mechanisms of cadaver kidney injury. Ultimately, better understanding of these mechanisms should provide a basis for treatment to prevent cadaver kidney injury and improve graft function.

描述（由申请人提供）：移植后最初几天内，尸体肾脏的功能范围从接近零到正常。大多数肾脏最初功能较差，最终恢复了足够的功能。然而，延迟的功能会产生重要的不利后果。它使住院和免疫抑制治疗复杂化。此外，当移植后第一周需要透析时，延迟功能是移植物存活率差的主要相关因素之一。 目前的建议的目的是确定尸体供肾的具体变化，有助于延迟移植功能。目前，这些变化的性质在很大程度上是未知的。拟议的研究将采用微阵列技术来分析移植前获得的供体肾活检组织中的基因表达。最近开发的统计技术将被用来确定基因的表达在供体肾是最密切相关的植入后的头几天内的功能差。 通过微阵列分析的基因表达谱提供了一种无与伦比的筛选机制。由于楔形活检的可用性，这种方法可以更容易地应用于研究供肾损伤比任何其他问题在临床肾脏病学。在尸体肾中鉴定其表达与移植肾功能低下相关的基因将有助于进一步研究尸体肾损伤的机制。最终，更好地了解这些机制应该提供治疗的基础，以防止尸体肾损伤和改善移植肾功能。