Genomewide Expression Profiles of Rat Model Renal Isografts From Brain Dead Donors

Abstract

Because our experimental system is a good model of renal transplantation from brain dead or living human donors, our data may be useful for elucidating the pathologic processes involved and for identification of novel markers for graft dysfunction of renal transplantation.

Signal Transduction Pathways Involved in Brain Death-Induced Renal Injury

“…This significant ischemic state is marked by elevated serum lactate levels (8)(9)(10). Appropriate donor management with hemodynamic stabilization after brain death toward normotensive levels limits organ dysfunction (8,11) and decreases the severity of the inflammatory response after brain death, which is demonstrated by a decrease in the number of CD8-positive cells in glomeruli and interstitium (9) (4), S100b (12,13), (14,15), complement activation and coagulation disorders (16 (12,13). The timeprofile of release suggests a role for S100b in delayed reparative processes.…”

“…However, when compared to organs retrieved from living donors, deceased donor kidneys have a significantly increased risk of delayed graft function and inferior long-term graft survival (1)(2)(3). The unphysiological state of brain death followed by preservation and ischemia/reperfusion-induced injury (4,5) will damage the kidney graft-to-be. After transplantation, the functioning nephron mass is reduced, which leads to exhaustion of the remaining nephrons due to hyperfiltration trying to meet the metabolic needs (6) and result in accelerated dysfunction (7).…”

“…After transplantation, the functioning nephron mass is reduced, which leads to exhaustion of the remaining nephrons due to hyperfiltration trying to meet the metabolic needs (6) and result in accelerated dysfunction (7). Recent microarray studies have demonstrated upregulated expression of genes related to inflammatory responses and reparative mechanisms in kidneys after brain death (4,8)…”

Donor Ethnicity Influences Outcomes following Deceased-Donor Kidney Transplantation in Black Recipients

“…Studies in rat and human transplant models have demonstrated the presence of an early-phase inflammatory process in response to brain death that is characterized by upregulation of adhesion molecules, cytokines, chemokines, and heat-shock proteins (HSP). 32,33 Recently, Smith et al 34 demonstrated the presence of HSP polymorphisms between white and black populations that are associated with altered mRNA and protein levels. Given the ability of HSP to protect against cell damage, some of these polymorphisms may reduce an individual's tolerance to the cellular insults associated with brain death.…”

The implications of brain death in donor lung injury: investigation and blockade of the endothelin axis

“…[213] IRI leads to organ dysfunction through induction of cytokines, generation of free radicals and activation of immunocompetent cells. [213,214] Endothelial cell dysfunction secondary to IRI is key in chronic allograft dysfunction in hearts, [215] lungs, [25] livers, [216] and kidneys. [217] Early injury to cells occurs as a direct result of ischaemia, with impaired oxygen delivery, altered energy metabolism and accumulation of waste products.…”