Up-regulation of osteopontin, chemokines, adhesion molecule, and heat shock proteins in 1-hour biopsy from cardiac death donor kidneys.
OBJECTIVE
Since April 1979, 471 kidneys were retrieved from donors after cardiac death (DCD) using an in situ regional cooling technique, with excellent renal function and good long-term graft survival. However, the precise cascade of events following transplantation of DCD kidneys and the influence of ischemia-reperfusion injury remain unclear. In this study, we performed gene expression profiling using 1-hour biopsy samples from DCD kidneys versus those from living sources.


METHODS
All kidney grafts were procured at our center using an in situ regional cooling technique from DCD. Living donor kidneys (LD) were harvested by open nephrectomy. All graft biopsies were performed 1 hour after reperfusion (DCD n = 8, LD n = 9). We analyzed the expression profile of 20,173 genes.


RESULTS
One hundred seventy eight genes were up-regulated (>2-fold difference and DCD/LD > 1.5) and 120 down-regulated (<1/2-fold and LD/DCD > 1.5) in DCD kidneys. Expression of osteopontin (22.5 +/- 2.6-fold DCD vs 7.7 +/- 1.7 LD; P < .001), chemokines (CCL4 4.4 +/- 0.7 vs 2.5 +/- 0.3; P < .01), (CCL2 6.0 +/- 1.3 vs 2.8 +/- 0.5), CXCL1 (9.5 +/- 0.4 vs 2.0 +/- 0.2), and CXCL2 (16.7 +/- 5.3 vs 4.8 +/- 1.3; P < .05), adhesion molecule (ICAM-1 4.7 +/- 0.7 vs 2.5 +/- 0.4; P < .05), and heat shock proteins (HSPA1L 6.7 +/- 0.7 vs 1.6 +/- 0.3, HSPA1A 17.7 +/- 2.6 vs 2.4 +/- 0.5, HSPA1B 13.3 +/- 0.2 vs 3.0 +/- 0.7, HSPA5 6.7 +/- 0.8 vs 3.2 +/- 0.3, HSPB1 2.9 +/- 0.2 vs 1.0 +/- 0.1, and HSPH1 19.4 +/- 3.0 vs 5.9 +/- 1.1; P < .001) were up-regulated in the kidneys from DCD.


CONCLUSIONS
This report analyzed global gene expression using 1-hour biopsy samples from DCD kidneys. These results may provide new insight into the identification of novel target genes for the development of therapeutic approaches and for determining graft viability of kidneys from DCD.
Kusaka
M
M
Department of Urology, Fujita Health University School of Medicine, Aichi, Japan. mkusaka@fujita-hu.ac.jp
Kuroyanagi
Y
Y
Mori
T
T
Sasaki
H
H
Maruyama
T
T
Hayakawa
K
K
Shiroki
R
R
Kurahashi
H
H
Hoshinaga
K
K
D001706:Biopsy; D015815:Cell Adhesion Molecules / Q000235:genetics*; D018925:Chemokines / Q000235:genetics*; D016757:Death, Sudden, Cardiac; D015536:Down-Regulation; D000091342:Endoplasmic Reticulum Chaperone BiP; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D007668:Kidney / Q000473:pathology / Q000502:physiology; D007672:Kidney Cortex / Q000473:pathology / Q000502:physiology; D053495:Osteopontin / Q000235:genetics*; D014019:Tissue Donors; D015854:Up-Regulation
D015815:Cell Adhesion Molecules; D018925:Chemokines; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D053495:Osteopontin