Kidney grafts from brain dead donors: Inferior quality or opportunity for improvement?

Abstract

Major improvements in immunosuppressive treatment, surgical techniques, and treatment of post-transplant complications have contributed considerably to improved outcome in renal transplantation over the past decades. Yet, these accomplishments have not led to similar improvements in transplant outcome when the results of living and deceased donors are compared. The enormous demand for donor kidneys has allowed for the increase in acceptance of suboptimal donors. The use of brain dead patients as organ donors has had a tremendous positive influence on the number of renal transplants. Unfortunately, the physiologically abnormal state of brain death has a negative effect on transplant outcome. The fact that transplanted kidneys derived from brain dead donors have a decreased viability indicates that potential grafts are already damaged before retrieval and preservation. In this review, we present an overview of the current knowledge of (patho)-physiological effects of brain death and its relevance for renal transplant outcome. In addition, several options for therapeutic intervention during brain death in the donor with the goal to improve organ viability and transplant outcome are discussed.

Expression of Complement Components Differs Between Kidney Allografts from Living and Deceased Donors

“…The persisting graft survival difference between living-and deceased-donor kidneys for renal transplantation 1,2 suggests that a significant potential to improve graft survival further lies in new approaches to overcome the deleterious effects of often inevitable longer cold ischemia times 3 and brain death. 4 Apart from further refining storage solutions and machine perfusion techniques, targeted therapy and modulation of specific pathways before organ retrieval, during cold storage or after implantation, could have beneficial effects and improve the outcome of deceased-donor kidney transplantation.…”

“…The persisting graft survival difference between living-and deceased-donor kidneys for renal transplantation 1,2 suggests that a significant potential to improve graft survival further lies in new approaches to overcome the deleterious effects of often inevitable longer cold ischemia times 3 and brain death. 4 Apart from further refining storage solutions and machine perfusion techniques, targeted therapy and modulation of specific pathways before organ retrieval, during cold storage or after implantation, could have beneficial effects and improve the outcome of deceased-donor kidney transplantation.To identify these specific pathways underlying the difference between pristine (normal histology, young donor age) deceased-and living-donor kidneys, we undertook this microarray study comparing implantation and posttransplantation protocol biopsies without rejection, in both deceased-and living-donor recipients. Previous studies using gene expression microarray experiments on implantation biopsies have demonstrated expression profile differences between living-and marginal deceaseddonor kidneys, 5-7 have not always been validated in independent data sets, 5,6 and did not always provide in-depth analyses of the pathways involved.…”

“…4 Apart from further refining storage solutions and machine perfusion techniques, targeted therapy and modulation of specific pathways before organ retrieval, during cold storage or after implantation, could have beneficial effects and improve the outcome of deceased-donor kidney transplantation.…”

Brain death-associated pathological events and therapeutic options

“…33 Lowdose vasopressin therapy, when compared to fluid volume replacement, improves blood pressure, decreases inotrope requirements and preserves levels of myocardial high energy phosphates, and allows for the reduction of catecholamine supply. 4 Administration of only crystalloid solutions results in the exacerbation of neurogenic pulmonary edema and frustrates pulmonary procurement. In therapy, both vasopressin and desmopressin can be used.…”

“…Hyperglycemia management enhances the hemodynamic performance of myocardium, reduces myocardial injury, and diminishes inotrope requirements by optimizing substrate utilization, reducing toxic circulating free fatty acids, direct inotropic and anti-apoptotic effects of insulin, as well as the potential to improving the calcium handling and beta-adrenergic properties of the myocyte. 4 Intensive insulin therapy in intensive care unit (ICU) patients is also associated with the prevention of newly acquired kidney injury, accelerated weaning from mechanical ventilation and the reduction of the inflammatory response. 38 …”