Elsevier

Transplantation Proceedings

Volume 38, Issue 10, December 2006, Pages 3347-3350
Transplantation Proceedings

Scientific contribution
Ischemia–reperfusion injury: Kidney
Up-Regulation of Osteopontin, Chemokines, Adhesion Molecule, and Heat Shock Proteins in 1-Hour Biopsy From Cardiac Death Donor Kidneys

https://doi.org/10.1016/j.transproceed.2006.10.099Get rights and content

Abstract

Aims

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.

Conclusion

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.

Section snippets

Materials and Methods

All kidney grafts were procured at our center using an in situ regional cooling technique from DCD. Living donor kidneys (LD) were procured by open nephrectomy. All graft biopsies performed 1 hour after reperfusion were obtained from the renal cortex (DCD n = 8, LD n = 9). All biopsy specimens were immediately submerged in RNAlater (Ambion) for storage. Biopsy specimens were homogenized and total RNA purified using an RNeasy Mini kit (Qiagen, Valencia, Calif, USA). The expression profile of

Results

One hundred seventy eight genes were up-regulated (>2-fold difference and DCD/LD >1.5; P < .05) 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 molecules (ICAM-1 4.7 ± 0.7 vs 2.5 ± 0.4; P < .05), and heat shock proteins (HSPs; HSPA1L 6.7 ± 0.7 vs 1.6 ± 0.3, HSPA1A 17.7 ± 2.6 vs 2.4 ± 0.5,

Discussion

The present study showed that DCD caused increased expression of chemokines, adhesion molecules, and the stress-related HSPs in grafts. Osteopontin, a potent chemoattractant for mononuclear cells that is up-regulated in various inflammatory states of the kidney, was markedly up-regulated in DCD grafts. Expression of osteopontin is known to be induced in the tubular epithelium by ischemia-reperfusion injury and renal allograft rejection.3, 4 However, the mechanistic pathway of increased

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