Kidney transplantation outcomes are adversely affected by ischemia-reperfusion injury, which occurs as a result of blood flow restrictions during the reperfusion stage of transplant surgery. In animal models of transplantation, females show increased tolerance to ischemia compared to males, but it is unclear whether sex disparities extend to human kidney transplantations. In this month's issue of the JCI, research led by Matthew Levine at the University of Pennsylvania linked female resilience to renal ischemia with protective effects of estrogen. Female mice displayed increased survival rates and lower levels of kidney injury compared to males following induced renal ischemia. The effects were attenuated in neutered females, but supplemental estrogen prior to the ischemic episode restored protection. Moreover, an analysis of over 46,000 human kidney transplantation outcomes associated greater failure rates in male compared to female transplant recipients. These findings suggest that improved female outcomes after kidney transplantation may be due to protective effects of estrogen, providing a mechanistic basis for potential therapeutic interventions for renal ischemia.
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