Background: Gender has been shown to have some impact on tolerance of ischemia-reperfusion injury (IRI) in animal models, with female mice having greater IRI tolerance. It is not clear whether this is due to a difference in the kidney itself, the inflammatory capacity of the animal, or a combination of the two. We wished to assess which factor had greatest influence on this gender difference.

Method: We performed renal transplantation in four groups of c57b/6 mice, with male kidneys being transplanted into either male or female recipients and female kidneys being transplanted into male or female reicipients. We waited 10 days, removed native kidneys, assessed baseline BUN after a week, and then performed standard renal IRI on the transplanted kidney and assessed BUN for 4 days after IRI. 25 mins of IRI was performed for 3 groups but 20 mins was used for the MtoM group due to intolerance of 25 mins IRI. At least 5 mice per group were analyzed.

Results: The controls yielded similar data to standard nontransplant IRI experiments with female to female transplant (FtoF) surviving 25 mins IRI with BUN rise but MtoM mice tolerating only 20 mins IRI to achieve similar BUN rise and with 25 mins being uniformly lethal. Because of shorter IRI time, the MtoM group is not displayed in Fig 1. In cross transplantation with subsequent 25 mins IRI, the FtoM group responded similarly to the MtoM group with all but one mouse being euthanized after 48 hours due to poor condition and BUN at maximal reading of 140. The MtoF group had slightly improved BUN relative to the FtoF group after 25 mins IRI (Fig 1), but the curves were similar between these groups.

Conclusion: There may be minor effects on donor gender but the predominant difference in tolerance of renal IRI between the genders appears not to be intrinsic to the kidney itself but rather within the host, likely within the inflammatory response to injury. Small nephron dosing differences may explain the slight improvement in the MtoF group relative to the FtoF group.

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