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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DK063127-01
Application #
6562360
Study Section
General Medicine B Study Section (GMB)
Program Officer
Flessner, Michael Francis
Project Start
2003-03-01
Project End
2005-02-28
Budget Start
2003-03-01
Budget End
2004-02-28
Support Year
1
Fiscal Year
2003
Total Cost
$158,833
Indirect Cost
Name
Stanford University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Hauser, Peter; Kainz, Alexander; Perco, Paul et al. (2005) Transcriptional response in the unaffected kidney after contralateral hydronephrosis or nephrectomy. Kidney Int 68:2497-507
Kainz, Alexander; Mitterbauer, Christa; Hauser, Peter et al. (2004) Alterations in gene expression in cadaveric vs. live donor kidneys suggest impaired tubular counterbalance of oxidative stress at implantation. Am J Transplant 4:1595-604
Hauser, Peter; Schwarz, Christoph; Mitterbauer, Christa et al. (2004) Genome-wide gene-expression patterns of donor kidney biopsies distinguish primary allograft function. Lab Invest 84:353-61