Abstract
Although iron is reported to be associated with the pathogenesis of chronic kidney disease, it is unknown whether iron participates in the pathophysiology of nephrosclerosis. Here, we investigate whether iron is involved in the development of hypertensive nephropathy and the effects of iron restriction on nephrosclerosis in salt- loaded stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP were given either a normal or high-salt diet for 8 weeks. Another subset of SHRSP were fed a high-salt with iron-restricted diet. SHRSP given a high-salt diet developed severe hypertension and nephrosclerosis. As a result, survival rate was decreased after 8 weeks diet. Importantly, massive iron accumulation and increased iron content were observed in the kidneys of salt-loaded SHRSP, along with increased superoxide production, urinary 8-Hydroxy-2′-deoxyguanosine excretion, and urinary iron excretion; however, these changes were markedly attenuated by iron restriction. Of interest, expression of cellular iron transport proteins, transferrin receptor 1 and divalent metal transporter 1, was increased in the tubules of salt-loaded SHRSP. Notably, iron restriction attenuated the development of severe hypertension and nephrosclerosis, thereby improving survival rate in salt-loaded SHRSP. Taken together, these results suggest a novel mechanism by which iron plays a role in the development of hypertensive nephropathy and establish the effects of iron restriction on salt-induced nephrosclerosis.
Highlights
The number of patients with chronic kidney disease (CKD) is increasing, and CKD is associated with increased risk of sudden death [1]
In order to investigate whether iron is involved in the development of hypertensive nephropathy in salt-loaded SHRSP, we assessed iron accumulation and intracellular iron transport proteins, such as transferrin receptor 1 (TfR1) and divalent metal transporter 1 (DMT-1), in the kidney of these groups
We show for the first time that dietary iron restriction attenuates the development of severe hypertension and nephrosclerosis, thereby improving survival rate in salt-loaded SHRSP
Summary
The number of patients with chronic kidney disease (CKD) is increasing, and CKD is associated with increased risk of sudden death [1]. Abnormal iron deposition is observed in the tubules of human chronic renal disease [3] and animal models of nephropathy [4,5,6]. We have recently reported that renal iron accumulation and expression of intracellular iron transport proteins, such as transferrin receptor 1 (TfR1) and divalent metal transporter 1 (DMT-1), are increased in the tubules of the well-established 5/6 nephrectomy rat model of CKD. We have shown that dietary iron restriction attenuates the development of renal damage in CKD model rats [7]. It is largely unknown whether iron and intracellular iron transport proteins participate in the pathophysiology of hypertensive nephropathy. The effects of iron restriction on the development of salt-induced nephrosclerosis remain unknown
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