Prolonged unilateral renal ischemia-reperfusion as a model for acute to chronic kidney injury in female mice

Acute kidney injury (AKI) is a significant risk factor for developing chronic kidney disease (CKD). Recent studies have highlighted notable gender differences in the susceptibility and expression of both AKI and CKD. The mechanisms underlying these differences remain unclear, and there is a lack of reliable models for studying the AKI-CKD transition in females. In this study, we evaluated various ischemia times in the unilateral renal ischemia-reperfusion injury (UIR) model in female mice to establish a model for studying the AKI-CKD transition. UIR was induced in the left kidneys of male and female C57Bl/6 mice. Kidney pathology and key injury markers were examined 28 days post-UIR. Comparable pathological changes were observed in female mice subjected to 50- and 60-min ischemia, similar to those in male mice subjected to 30-min UIR. Protein levels of key injury markers, including Vim-1, Krt8, and Acta2, were significantly increased in female mice subjected to 50- and 60-min UIR, comparable to male mice subjected to 30-min UIR, 28 days postinjury. In addition, an increase in mRNA expression of key kidney injury markers <i>Col1a1, Vim-1, FN</i>, and <i>Sox4</i>, along with a decline in <i>Slc34a1</i> expression, was observed in female mice subjected to 50- and 60-min UIR, similar to male mice subjected to 30-min UIR, at 28 days postinjury. Our findings suggest that the optimal ischemia time for inducing CKD changes in female mice is 50-60 min, compared to much shorter injury times in male mice.<b>NEW & NOTEWORTHY</b> Our findings identify a reliable timepoint at which female mice subjected to unilateral ischemia-reperfusion consistently develop CKD changes relative to much shorter duration in male mice. We provide a novel model to study the AKI-CKD transition in female mice.