Association between renal iron accumulation and renal interstitial fibrosis in a rat model of chronic kidney disease

• Published in: Hypertension research Vol. 38; no. 7; pp. 463 - 470
• Main Authors: Naito, Yoshiro, Fujii, Aya, Sawada, Hisashi, Oboshi, Makiko, Iwasaku, Toshihiro, Okuhara, Yoshitaka, Morisawa, Daisuke, Eguchi, Akiyo, Hirotani, Shinichi, Masuyama, Tohru
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.07.2015
• Subjects: Animals; Benzoates - pharmacology; Blood Pressure; Fibrosis - pathology; Gene expression; Gene Expression - drug effects; Hypertension; Iron - metabolism; Iron Chelating Agents - pharmacology; Kidney - metabolism; Kidney - pathology; Kidney diseases; Male; Nephrectomy; Nephritis, Interstitial - pathology; Proteinuria - drug therapy; Proteinuria - metabolism; Rats; Rats, Sprague-Dawley; Renal Insufficiency, Chronic - genetics; Renal Insufficiency, Chronic - metabolism; Renal Insufficiency, Chronic - pathology; Rodents; Triazoles - pharmacology
• ISSN: 0916-9636; 1348-4214
• DOI: 10.1038/hr.2015.14

Iron accumulation is associated with the pathophysiology of chronic kidney disease (CKD). Renal fibrosis is a final common feature that contributes to the progression of CKD; however, little is known about the association between renal iron accumulation and renal interstitial fibrosis in CKD. Here we investigate the effects of iron chelation on renal interstitial fibrosis in a rat model of CKD. CKD was induced by 5/6 nephrectomy in Sprague-Dawley rats. At 8 weeks after operation, 5/6 nephrectomized rats were administered an oral iron chelator, deferasirox (DFX), in chow for 8 weeks. Other CKD rats were given a normal diet. Sham-operative rats given a normal diet served as a control. CKD rats exhibited hypertension, glomerulosclerosis and renal interstitial fibrosis. Iron chelation with DFX did not change hypertension and glomerulosclerosis; however, renal interstitial fibrosis was attenuated in CKD rats. Consistent with these findings, renal gene expression of collagen type III and transforming growth factor-β was increased in CKD rats compared with the controls, while iron chelation suppressed these increments. In addition, a decrease in vimentin along an increase in E-cadherin in renal gene expression was observed in CKD rats with iron chelation. CKD rats also showed increased CD68-positive cells in the kidney, whereas its increase was attenuated by iron deprivation. Similarly, increased renal gene expression of CD68, tumor necrosis factor-α and monocyte chemoattractant protein-1 was suppressed in CKD rats with iron chelation. Renal iron accumulation seems to be associated with renal interstitial fibrosis in a rat model of CKD.