Renal filtration and excretion of aluminium in the rat: dose-response relationships and effects of aluminium speciation

Abstract

The known toxicity of aluminium, and the toxicity of agents (such as desferrioxamine) used to remove alumini um from the body, has prompted us to investigate whether there may be ways of enhancing aluminium excretion by exploiting the normal renal handling of aluminium. Aluminium (as sulphate or citrate) was administered intravenously to conscious rats at doses ranging from 25 μg (0.93 μmol) to 800 μg (29.6 μmol) aluminium, and alu minium excretion was monitored over the following 2 h. Measurements of the filterability of aluminium from the rat plasma, and the glomerular filtration rate (inulin clearance), enabled us to calculate the filtered load of alu minium, and hence determine aluminium reabsorption.

At all doses of administered aluminium, that adminis tered as sulphate was excreted less effectively than that administered as citrate. This difference was attributable to the much greater filterability of aluminium administered as citrate. However, for any given filtered load, the excre tion of aluminium administered as citrate was not signifi cantly different (in either fractional or absolute terms) from the excretion of aluminium administered as sulphate.

It seems likely that, following aluminium sulphate administration, the filtered aluminium may be an alumini um citrate form which is then reabsorbed in the same way as aluminium administered as citrate.

It is thus apparent that aluminium removal from the body could be further enhanced if it were possible to pre vent the tubular reabsorption of the aluminium species which is so effectively filtered following aluminium citrate administration.