The kidney filters and reabsorbs a metabolically important amount of iron. The renal mechansim of iron reabsorption is not known. The divalent metal transporter DMT1 (also known as DCT1 or NRAMP2) transports iron, copper and manganese and to a lesser extent other divelent metals, but not calcium or magnesium. We have shown that DMT1 is expressed on the apical membrane of early distal convoluted tubule and cortical and outer medullary collecting ducts indicating that it may be involved in iron reabsorption in these segements (Wareing et al. 2000; Ferguson et al. 2001). The Belgrade (b) rat is homozygous for a mutation causing loss of DMT1 function. This study aimed to determine the effect of this mutation on renal divalent metal handling.

Experiments were carried out in accordance with UK legislation. Male Wistar, heterozygote (b/+) and homozygous (b/b) Belgrade rats (all groups n = 4) were maintained on a synthetic diet containing 220 mg kg^-1 iron and housed in metabolism cages. 24 h collections of urine were made and analysed by inductively coupled plasma mass spectrometry. Analysis of variance revealed b/+ and b/b rats excreted equivalent amounts of urine (osmoles) sodium and potassium, although these variables were significantly reduced compared with Wistar rats. Urinary iron outputs of b/+ and b/b rats were not different; however, both groups excreted significantly less iron than Wistar rats. b/b rats excreted significantly more calcium and significantly less magnesium than b/+ or Wistar rats. Urinary copper and zinc excretion did not differ between b/+ and b/b rats, but was significantly higher for Wistar rats. In contrast, output of manganese was not different between groups.

In conclusion, b/+ and b/b rats have a similar profile of renal ion excretion, but these profiles are surprisingly different from the pattern observed for Wistar rats. Therefore possession of the mutant allele may be responsible for these phenotypes.