Research Group
- Dr. Debra Hullett, Principal Investigator
- Alexander Pietsch, Research Associate
- Dr. Bryan Becker, Collaborator
Location
- University of Wisconsin, Madison, USA
Title
- Effect of Vitamin D on Renal Allograft Function
Graft failure following transplantation results from either acute or chronic rejection. There are currently many immunosuppressive agents that are effective at preventing acute rejection. There are no such reagents for the prevention of chronic rejection. In the kidney, chronic rejection is characterized by the development of fibrotic changes, which include interstitial fibrosis, tubular atrophy, glomerulosclerosis, and concentric intimal hyperplasia. This process has been termed chronic allograft nephropathy (CAN).
1,25-Dihyroxyvitamin D3 [1,25-(OH)2D3] is the active metabolite of vitamin D. Its long-known function is to regulate calcium metabolism. Recent evidence suggests that 1,25-(OH)2D3 also regulates the growth and differentiation of many cell types, and in particular that 1,25-(OH)2D3 regulates immune responses. We have shown that 1,25-(OH)2D3 treatment prolongs allograft survival. Importantly, we have shown in a retrospective study that renal transplant patients who received 1,25-(OH)2D3 supplementation because of renal insufficiency had stabilized graft function.
The mechanisms that lead to the development
of CAN are unknown, but are thought to involve both immune and non-immune
factors. The cytokine transforming growth factor beta (TGF�) has been implicated in the
pathogenesis of the fibrotic changes in
The experiments proposed in this application should lead to a greater understanding of the mechanisms underlying CAN and may identify new targets for therapy.