Effect of citrate on plasma aluminium concentration and aluminium excretion in the rat

Abstract

1. Plasma aluminium concentration and urinary aluminium excretion were monitored for 4.5 h in rats after the administration of 25 μg or 800 μg of aluminium as an intravenous bolus, either as aluminium chloride or as aluminium citrate (i.e. aluminium chloride together with sodium citrate). 2. Immediately after the bolus aluminium administration, the plasma aluminium concentration was higher in the groups given aluminium chloride than in those which received aluminium citrate, although the difference was significant (P<0.05) only for the 25 μg dose. This difference between aluminium chloride and citrate indicates that the citrate form has a higher volume of distribution (i.e. is able to leave the plasma). The calculated volume of distribution for the 25 μg dose of aluminium chloride (17.5 ml) was similar to the plasma volume of the rats used (15 ml). 3. In experiments in vitro, the ultrafilterability of aqueous solutions of aluminium chloride and aluminium citrate were compared. Only 1.05 ± 0.09% of the aluminium chloride solution was ultrafilterable (aluminium concentration 28 200 ± 730 ng/ml), whereas 97.3 ± 2.4% of the aluminium citrate was ultrafilterable (aluminium concentration 42000 ± 370 ng/ml). When the filterability of aluminium in plasma was examined, the aluminium chloride ultrafilterability was identical with that in aqueous solution (1.06 ± 0.13%, aluminium concentration 19 800 ± 2956 ng/ml), but the aluminium citrate was 79.8 ± 7.1% ultrafilterable (aluminium concentration 10125 ± 591 ng/ml). 4. The differences in ultrafilterability in vitro were reflected in the urinary aluminium excretion in vivo. Even though the plasma levels of aluminium were lower in the groups that received citrate, the aluminium administered as citrate was excreted much more rapidly than the aluminium chloride. With the 25 μg dose of aluminium as chloride, 13.39 ± 0.87 μg (i.e. 53%) was excreted in 4.5 h, whereas with the citrate form 21.85 ± 3.05 μg (87%) was excreted in 4.5 h (P<0.01). For the 800 μg dose of aluminium, the excretion was 160.03 ± 18.40 μg (chloride) and 451.16 ± 36.76 μg (citrate) (P<0.01). 5. It is clear that renal aluminium excretion is much more efficient if aluminium citrate is administered rather than aluminium chloride. The findings raise the possibility that intravenous citrate could have therapeutic applications in patients who have accumulated aluminium.