Background: The mechanism of anemia in cardio-renal anemia syndrome remains completely unknown. We have previously reported that impaired intestinal iron transporters may contribute to the mechanism of anemia in heart failure (HF) using HF model rats. In this study, we assessed intestinal iron transporters in chronic kidney disease (CKD) model rats to investigate the association of intestinal iron transporters in the mechanism of cardio-renal anemia syndrome. Methods and Results: CKD was induced by 5/6 nephrectomy in Sprague-Dawley rats. Sham-operated rats served as a control. After 24 weeks surgery, CKD rats exhibited normocytic normochromic anemia and normal serum erythropoietin levels despite of anemia. Serum iron levels were decreased in CKD rats compared with the controls. Of interest, intestinal expression of critical iron importers such as duodenal cytochrome b and divalent metal transporter 1 was decreased in CKD rats compared with the controls. On the other hand, intestinal expression of ferroportin, an intestinal iron exporter, was not different in the control and CKD groups. Moreover, hepatic expression of hepcidin, a regulator of iron homeostasis, did not differ between the control and CKD groups. Conclusion: Impaired intestinal iron transporters may be associated with the mechanism of anemia in cardio-renal anemia syndrome.
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