Abstract
Introduction: Superior female tolerance of ischemia in mice is a known phenomenon but not well characterized. We wished to determine if murine gender differences in renal ischemia reperfusion injury (IRI) tolerance were intrinsic or extrinsic to the kidney and wished to determine if hormonal therapy could yield improved IRI tolerance. Methods: Murine c57B6 renal transplants were performed from male and female donors into male and female recipients, followed by native nephrectomy and later standardized 25 minutes of IRI of the transplanted kidney. Renal function was assessed daily for 4 days after IRI by BUN measurement and then renal injury and fibrosis was scored at 30 days after IRI by automated Sirius Red staining. Mice were then treated with 1mg/kg of 17-β estradiol or vehicle at 16 and 0.5 hours prior to 28 minutes of renal IRI and the same functional and structural assessments were made. Results: Female recipients of both male and female had similar BUN curves after IRI and significantly lower BUN that male recipients of either female or male kidneys (p<0.01). This demonstrated that female recipient phenotype and not female donor phenotype was protective of renal IRI. Similarly, fibrosis among female recipients of either gender kidney was significantly less than male recipients of either gender kidney after equivalent IRI (P< 0.01). Female mice treated with 17-β estradiol prior to renal IRI had significantly improved renal function after equivalent IRI demonstrating the estrogen treatment is protective in female mice (Fig 1).Figure: No Caption available.Conclusions: Female recipient gender is protective of renal IRI regardless of donor gender. This implies that an altered reperfusion response to IRI is likely responsible for the difference in IRI susceptibility and in congenic mice a hormonal effect is most likely. This is further supported by demonstration that treatment with 17-β estradiol mitigates renal IRI injury in terms of early function and fibrosis formation.
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