The renal handling of δ-aminolevulinic acid in normal and lead-poisoned rabbits

Abstract

This article describes the renal handling of δ-aminolevulinic acid (ALA) in normal and lead-exposed rabbits. In normal animals, fractional reabsorption (FR) of filtered ALA amounted to 85 ± 6% (SD), as measured with [ 14C]ALA. To validate the use of [ 14C]ALA, its clearance was compared in six further experiments with that of ALA determined by a new gas-liquid chromatographic procedure; this assay yielded a mean FR of 89% ± 12. The high FR observed in rabbits contrasts with preliminary results in humans where FR was much lower. The reaborptive process in rabbits can be saturated, although only at concentrations of plasma ALA much higher than those reported even in severe lead poisoning. Reabsorption is also independent of urine flow. Presumably mediation by a carrier system is involved; this differs from carrier systems responsible for transport of several α-amino acids, none of which affect transport of ALA. The daily sc administration of lead, sufficient to increase urinary ALA 50-fold, did not alter FR; however, poisoning of tubules with either CdCl 2 or uranyl acetate greatly reduced FR. We conclude that in normal rabbits, the renal ALA reabsorptive process is a high capacity, low affinity, carrier-mediated system. The increased excretion of ALA seen in lead-poisoned animals cannot be attributed to inhibition of ALA reabsorption and must therefore reflect extrarenal effects of lead.