Donor Kidney Gene Expression and Delayed Graft Function

描述(申请人提供)：移植后最初几天的身体肾脏功能从接近零到正常。大多数初始功能不佳的肾脏最终会恢复正常的功能。然而，功能延迟会产生严重的不良后果。它延长了住院时间，并使免疫抑制治疗复杂化。此外，当移植后第一周需要透析时，功能延迟是移植物存活率差的主要相关因素之一。 目前这项提议的目的是确定身体供体肾脏中导致移植肾功能延迟的具体变化。目前，这些变化的性质在很大程度上是未知的。拟议的研究将使用微阵列技术来分析植入前获得的供体肾脏活检组织中的基因表达。最近发展起来的统计技术将被用来确定在移植后的头几天，供体肾脏中表达与功能不良最密切相关的基因。 基因表达谱微阵列分析提供了一种无与伦比的筛选机制。由于楔形活检的可用性，这种方法比临床肾病学中的任何其他问题更容易应用于供体肾损伤的研究。发现在身体肾脏中表达与移植物功能不良相关的基因有助于进一步研究身体肾脏损伤的机制。最终，更好地了解这些机制应该为预防身体肾脏损伤和改善移植物功能的治疗提供基础。

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.