Donor Kidney Gene Expression and Delayed Graft Function

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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.