Heme Oxygenase in Delayed Graft Function in Kidney Transplant
The efficacy of the HO pathway and the therapeutic use of CO in DGF in kidney transplantation is based on substantial clinical and preclinical data developed over the last forty years. Data from Phase 1 and Phase 2 clinical trials of CO using a different means of delivery point to therapeutic potential. In addition, both the up-regulation of HO and the exogenous administration of CO have been shown to reduce delayed graft function as well as improve clinical signs including renal function in a number of large and small animal models of kidney transplantation, as well as in animal models of the transplantation of other organs.
The primary mechanism of action are anti-inflammatory and anti-apoptotic. The HO pathway acts in an anti-inflammatory manner by down-regulating genes associated with inflammation (NFκB, VCAM-1, and ICAM-1) and in an anti-apoptotic manner by increasing key anti-oxidant pathways (Nrf-2, HO-1). Please see the Citations for more information..
The targeting of the heme oxygenase pathway to reduce DGF in kidney transplantation could potentially provide a much-needed therapeutic intervention for these patients.