Inverse correlation of kidney interstitial cells expansion with hemoglobin level and erythropoietin expression in single and repeated kidney ischemic/reperfusion injury in mice

Ischemic/reperfusion injury (IRI) causes acute kidney injury (AKI) that may lead to chronic kidney disease (CKD). We investigated the correlation between kidney interstitial cells expansion, hemoglobin level, and erythropoietin expression as the chronic effects of single and repeated kidney IRI in mice. We created IRI model using male Swiss mice by clamping bilateral pedicle renal. Subjects were divided into 4 groups that contained 6 mice each: Control/sham operation (SO), single acute IRI (IR1), single chronic IRI (IR12), and repeated IRI (IR7-12). Our results showed that single chronic and repeated IRI significantly increased tubular injury score, decreased hemoglobin level, and increased erythropoietin expression compared to control. Lower hemoglobin level in all groups compared to control was associated with erythropoietin resistance. In single chronic and repeated kidney IRI, there were decreased creatinine level compared to control. Decreased creatinine levels from group IR1 to IR12 suggesting repair phase of IRI starting on day 7 occurred in group IR12. A macrophage marker, CD68, and an inflammatory mediator marker, MCP-1, significantly increased in all IR groups suggesting inflammation occurred due to IRI. In conclusion, chronic and repeated kidney IRI induced interstitial cells expansion and inflammation which associated with anemia.