title: Dietary iron restriction prevents further deterioration of renal damage in a chronic kidney disease rat model.
abstract: OBJECTIVE
  Iron accumulation is associated with the pathogenesis of chronic kidney disease (CKD). However, little is known about the effects of isolated iron restriction against CKD. We have recently reported that iron restriction prevents the development of renal damage in the well established 5/6 nephrectomy rat model of CKD. Herein, we investigated the therapeutic effects of iron restriction on preexisting hypertension and renal damage in a rat model of CKD.
  
  
  METHODS
  CKD was induced by 5/6 nephrectomy in Sprague-Dawley rats. After surgery, 5/6 nephrectomized rats were given an iron-restricted diet from 1 day to 16 weeks for prevention protocol or from 8 to 16 weeks for rescue protocol. Other CKD rats were given a normal diet.
  
  
  RESULTS
  At 16 weeks after surgery, CKD rats developed hypertension and renal damage. Early intervention with iron restriction prevented the development of hypertension and vascular remodeling. By contrast, late intervention with iron restriction did not remarkably ameliorate preexisting hypertension and vascular remodeling in CKD rats. On the contrary, late intervention with iron restriction prevented further progression of preexisting renal damage in CKD rats. Interestingly, iron restriction led to increased urinary sodium and decreased urinary potassium excretions in CKD rats. Moreover, iron restriction markedly attenuated renal expression of nuclear mineralocorticoid receptor and Rac1 activity in CKD rats.
  
  
  CONCLUSIONS
  Iron restriction prevented further deterioration of preexisting renal damage. The beneficial effects of iron restriction on renal damage seem to be associated with inhibition of renal mineralocorticoid receptor signaling.
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, Japan. ynaito@hyomed.ac.jp
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Naito
authors.forename: Aya
authors.initials: A
authors.lastname: Fujii
authors.forename: Hisashi
authors.initials: H
authors.lastname: Sawada
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hirotani
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Iwasaku
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Okuhara
authors.forename: Akiyo
authors.initials: A
authors.lastname: Eguchi
authors.forename: Mitsumasa
authors.initials: M
authors.lastname: Ohyanagi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tsujino
authors.forename: Tohru
authors.initials: T
authors.lastname: Masuyama
mesh_terms: D000818:Animals; D006973:Hypertension / Q000209:etiology / Q000517:prevention & control; D007501:Iron / Q000008:administration & dosage*; D007677:Kidney Function Tests; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000178:diet therapy* / Q000517:prevention & control; D014131:Trace Elements / Q000008:administration & dosage*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D018161:Receptors, Mineralocorticoid; D014131:Trace Elements; D007501:Iron; C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein