Abstract 13960: Dietary Iron Restriction Prevents and Rescues Renal Injury in a Rat Model of Chronic Kidney Disease
Background: Iron accumulation is associated with the pathogenesis of cardiovascular disease and chronic kidney disease (CKD). However, little is known about the effects of iron restriction against these diseases. Here, we investigated the effects of dietary iron restriction on hypertension and renal injury in a rat model of CKD.
Methods and Results: CKD was induced by 5/6 nephrectomy in Sprague-Dawley rats. After operation, 5/6 nephrectomized rats were given iron-restricted diet from 1 day to 16 week for prevention protocol or from 8 week to 16 week for rescue protocol. Other CKD rats were given a normal diet. Sham-operative rats given a normal diet served as a control. CKD rats developed hypertension, proteinuria, glomerulosclerosis, podocyte injury, and tubular dilatation. In contrast, dietary iron restriction prevented the development of hypertension and kidney injury after 16 weeks diet. Iron restriction suppressed vascular hypertrophy, fibrosis, and inflammation in CKD rats. The phosphorylation of Akt and endothelial nitric oxide synthase was decreased in the aorta of CKD rats, whereas those changes were ameliorated by iron-restricted diet. In preexisting renal injury and hypertension in CKD, 8 weeks iron-restricted diet did not attenuate hypertension and vascular remodeling, while renal injury was ameliorated by iron restriction. Of interest, dietary iron restriction immediately led to increased urinary sodium excretion in CKD rats. Increased expression of nuclear mineralocorticoid receptor (MR) and Rac1 activity in the CKD kidney were significantly suppressed by iron restriction.
Conclusions: In conclusion, iron restriction prevents the development of hypertension and renal injury, and rescues preexisting renal injury. These beneficial effects of iron restriction on renal injury seem to be associated with the inhibition of renal MR signaling.
- © 2012 by American Heart Association, Inc.