Analysis of Donor Biopsy Tissue Samples at the Time of Kidney Transplant

• Primary endpoint for Aim 1 is the incidence of early organ dysfunction, defined by standard criteria for each organ defined as the need for dialysis within 7 days after transplant [ Time Frame: 7 days ] [ Designated as safety issue: No ]
  
• Primary endpoint for Aim 2 is the incidence of biopsy proven acute cellular rejection within the first 12 months after transplant [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  

• Serum Creatinine [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  Correlation between proinflammatory mediators at the time of transplantation and renal function as measured by serum creatinine
  
  
• Incidence of chronic allograft nephropathy [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  Correlation between proinflammatory mediators at the time of transplantation and incidence of chronic allograft nephropathy
  
  

Procedure: Kidney Biopsy
biopsy of transplant kidney

Background:

Early post-transplant kidney function can be attributed to inherent donor characteristics, damage from storage, and perioperative events and recipients factors. The incidence of severe injury to the transplant kidneys is 10-25% in the early post-transplant period. In addition, milder forms of early transplant kidney injury can impact on long term allograft function. Severe transplant kidney injury in the immediate post-transplant period has been hypothesized to be associated with higher rates of rejection.

Hypothesis:

In the current investigation, we would like to test the hypotheses that 1) mRNA and microRNA expression of proinflammatory genes in donor tissues is a risk factor for development of early kidney transplant dysfunction and 2) early inflammatory mRNA and microRNA expression in the allograft is associated with subsequent activation of cell mediated immunity as evidenced by increased incidence of acute rejection episodes and increased expression of cell mediated immunity genes during the first year post-transplant.

Aims:

Aim 1: Test the association between proinflammatory mRNA and microRNA expression in donor samples and subsequent development of early organ dysfunction in the immediate period following transplantation.

Aim 2: Test the association of mRNA and microRNA expression of proinflammatory mediators in the transplanted organ in the immediate pre and post-reperfusion period with subsequent incidence of acute rejection and expression of genes involved in cell mediated immunity.