In vivo characterization of renal iron transport in the anaesthetized rat

Iron (Fe2+/3+) is an integral part of a diverse array of biologically active molecules, which form key components of homeostatic processes that are central to life. As part of the porphyrin group of haem it is a fundamental constituent of haemoglobin and the cytochromes (Alfrey, 1992; Didonato & Sarkar, 1997; Ponka, 1999). It is also a component of the non-haem prosthetic groups in enzymes of the electron transport chain, e.g. NADH-coenzyme Q reductase. However, the reactive properties that make iron desirable from a biochemical standpoint are precisely those that make it potentially hazardous. Because of this it is critical that the total amount of iron in the body is tightly regulated and the concentration of free, ionized Fe2+ or Fe3+ is minimal. Thus, most of the iron circulating in the blood is bound to the plasma protein transferrin (Tf) and within cells iron is tightly bound to ferritin. In this way the amount of free iron is tightly controlled and is thought to be very low. It is widely held that control of iron in the body is mainly dependent on tight regulation of gastrointestinal (GI) uptake from the diet to balance iron loss via GI and biliary routes. Although renal excretion is central to the control of the divalent cations calcium (Ca2+) and magnesium (Mg2+), it is thought to play little, if any, role in regulating iron levels. However, this assumption must be questioned because it is clear from the paucity of literature relating to renal iron handling that little is actually known about how the kidney handles iron. The current dogma is that loss is unaltered in response to altered dietary iron content or during disease states. An exception is proteinuria when iron bound to protein is lost in the urine (Alfrey & Hammond, 1990; Alfrey, 1992). Under normal circumstances iron is lost via the kidneys, but whether the kidneys exert control over the amount of iron excreted is unclear. There is evidence to suggest that renal tubular cells do transport iron although whether this process is regulated is unknown (for example see Blumenthal et al. 1994). Recent, molecular biology experiments have shown that large amounts of mRNA encoding the divalent metal transporter DMT1 are present in the kidney. As well as iron, this protein transports several other divalent metals, but does not transport calcium or magnesium. Interestingly, DMT1 mRNA has been shown to increase in response to a decrease in dietary iron, suggesting that the kidney may adapt to altered iron availability (Gunshin et al. 1997). Given the lack of data concerning renal iron handling and the discovery of DMT1, the aims of the current study were to determine and characterize the nephron sites of iron reabsorption in the rat by in vivo micropuncture.