The influence of organ donor factors on early allograft function

Abstract

Postischaemic acute renal allograft failure is among the main risk factors for reduced transplant survival. Although new immunosuppressive protocols have reduced the number of acute rejections, the incidence of acute renal failure remained unchanged. On the basis of histomorphology it is not possible to predict donor kidneys at risk of subsequent failure. Some factors are associated with failure, but even combinations of these risk factors can not precisely predict the development of acute renal failure. Studies have therefore evaluated the influence of demographic donor and recipient factors on acute renal failure. New biotechnology and data mining tools are currently being used to study and identify the molecular predictors of acute renal failure. Recent studies showed that donor factors contributed to approximately 40% of the variability in early allograft function. Deductive approaches identified some isolated molecular targets, such as adhesion molecules, as risk factors. Explorative analysis of the entire human genome, however, identified several predictive clusters of genes, which can be functionally grouped into categories such as cell death, stress response, cell adhesion, transcription factors, inflammatory response or cell cycle-related genes. Based on this information, preventative strategies using antisense oligonucleotides or antibodies were adopted. Clinical studies identified the use of catecholamines in the organ donor as beneficial. All these efforts aim to reduce renal tubular damage. A detailed analysis of the molecular events and pathways of renal gene expression in the donor and after reperfusion, together with sophisticated data analysis tools, will provide new insights into the pathophysiology of acute renal failure.