Effect of lithium on renal transport and utilization of alpha-ketoglutarate in the rat

Experiments were carried out in the intact functioning rat kidney to study the effect of lithium on both the renal transport of alpha-ketoglutarate (alpha-KG) along the nephron by micropuncture techniques and the renal uptake and peritubular transport of alpha-KG by measuring the renal blood flow, the urinary flow and the rate of renal alpha-KG delivery, filtration, reabsorption or secretion and excretion. At endogenous plasma alpha-KG concentration, 2.3 mM plasma lithium caused an increase in the fractional excretion of alpha-KG, whereas 4.6 mM plasma lithium led to a net secretion of alpha-KG. The micropuncture data indicate that this secretion occurred between the late proximal and the distal tubule, i.e., in the pars recta and/or in the loop of Henle. When plasma alpha-KG concentration was elevated, the two doses of lithium used inhibited the reabsorption of alpha-KG both in the proximal tubule and in the pars recta and/or the loop of Henle. Renal arteriovenous measurements reveal that, at low plasma alpha-KG concentrations, lithium caused a significant decrease in both the renal uptake of alpha-KG and the peritubular transport of this organic anion. These results suggest that the alpha-KG secreted in the pars recta and/or the loop of Henle was synthesized within the renal cells of the latter segments and not transported from the blood to the tubular lumen. At higher plasma alpha-KG concentrations, both the peritubular transport and the renal reabsorption were reduced by lithium.