In vivo characterization of renal iron transport in the anaesthetized rat

Abstract

In vivo microinjections of 55FeCl3 were made to assess renal iron (Fe2+/3+) transport in the anaesthetized rat. Following microinjection into proximal convoluted tubules (PCTs), 18·5 ± 2·9 % (mean ± s.e.m., n= 11) of the 55Fe was recovered in the urine. This recovery was not dependent on the injection site indicating that iron is not reabsorbed across the surface convolutions of the proximal tubule. Following microinjection into distal convoluted tubules (DCTs) 46·1 ± 6·1 % (n= 8) of the injected 55Fe was recovered. Taken together the recovery data from the PCT and DCT microinjection studies indicate that the transport of iron occurs in the loop of Henle (LH) and collecting duct system. In vivo luminal microperfusion was used to examine iron transport by the LH in more detail. In tubules perfused with 7 μmol l−155FeCl3, 52·7 ± 8·3 % (n= 8) of the perfused 55Fe was recovered in the collected fluid, indicating significant iron reabsorption in the LH. Addition of copper (Cu2+ as 7 μmol l−1 CuSO4), manganese (Mn2+ as 7 μmol l−1 MnSO4) or zinc (Zn2+ as 7 μmol l−1 ZnSO4) to the perfusate did not affect reabsorption of water, Na+ or K+, but increased recovery of 55Fe to 83·5 ± 6·8 % (n= 8, P < 0·04), 75·8 ± 5·9 (n= 6, not significant, n.s.) and 67·9 ± 3·8; (n= 9, n.s.), respectively. Thus, iron transport in the LH can be reduced by the addition of copper or manganese to the luminal perfusate suggesting that these ions may compete with iron for a common transport pathway. However, this pathway may not be shared by zinc.

Role of the kidney in iron homeostasis: renal expression of Prohepcidin, Ferroportin, and DMT1 in anemic mice

“…Since it has been reported in the literature that iron-restricted diets are associated with high renal DMT1 expression and a decrease in urinary iron (34), our evidence of the coincident localization of iron proteins and iron deposits under anemia might indicate the reabsorption of iron from glomerular ultrafiltrate when iron demand is high. The purpose of this mechanism could be the provision of iron to renal cells for their metabolic activity and to help maintain iron homeostasis, emphasizing the importance of renal physiology in hematological processes.…”

“…Although kidney is not usually associated with serum iron balance, several studies found renal DMT1 expression in mice and rats, suggesting that this organ may have a role in iron homeostasis (4,10,33). Furthermore, Wareing et al (34) reported a decrease in urinary iron levels, suggesting iron reabsorption in renal tubules.…”

“…Renal excretion is central to the control of other divalent cations, but little is actually known about how the kidney handles iron. A few years ago Wareing et al (34) reported not only that a significant amount of serum iron is available for glomerular ultrafiltration, but also that most of the filtered iron is reabsorbed in renal tubules. However, it is unclear whether this organ exerts any control over the amount of iron excreted (34).…”

Acute study of interaction among cadmium, calcium, and zinc transport along the rat nephron in vivo

“…Using microperfusion of 55 Fe, Wareing et al (34) demonstrated significant reabsorption of Fe 2ϩ in the LH and that this reabsorption could be mediated by DMT1 (10,34). Thus it is reasonable to conclude that, like with Fe 2ϩ , Cd 2ϩ is transported, at least in part, by DMT1 in the apical membrane of the LH, in its TAL segment where DMT1 has been shown to be present (10).…”

“…Since their study, a divalent metal transporter (DMT1) has been cloned (18) and immunolocalized to the apical membrane of the thick ascending limb (TAL), distal tubule (DT), and the cortical collecting tubule (CCT) of the rat nephron (11), suggesting a role for this transporter in the renal handling of divalent metal cations. In a recent study, Wareing et al (34) have clearly demonstrated in the rat that DMT1 can transport Fe 2ϩ along the loop of Henle (LH) and distal tubule. Besides Fe 2ϩ , DMT1 also transports Cd 2ϩ and Zn 2ϩ (18).…”