MECHANISM OF LITHIUM-INDUCED RENAL TUBULAR-ACIDOSIS

Abstract

The effect of LiCl administration on urinary acidification was studied in dogs. Li-treated dogs developed hyperchloremic metabolic acidosis with alkaline urine. HCO3 loading resulted in a normal increase in urinary PCO2 in normal dogs but failed to produce the same response in Li-treated dogs. The HCO3 titration curve of Li-treated dogs revealed a small leak of HCO3 at low plasma levels of HCO3; at high plasma levels HCO3 reabsorption was significantly higher in Li-treated dogs. This pattern of HCO3 reabsorption was identical to that described in classic distal renal tubular acidosis. Sodium sulfate administration resulted in a normal urinary acidification in Li-treated dogs. It is possible that Li administration induced distal renal tubular acidosis by allowing excessive back-diffusion of acid. The excessive back-diffusion of acid would result in a low urinary PCO2 during HCO3 loading. Sodium sulfate administration, by increasing the negative intratubular potential, restricted back-diffusion of H+ and thereby resulted in a normal acidification in Li-treated dogs. Postureteral obstruction in the kidney failed to increase urinary PCO2 during HCO3 loading and lowered urinary pH with sodium sulfate. It is possible that a low urinary PCO2 during HCO3 loading occurred as a consequence of either diminished H+ secretion (postobstructed kidney) or excessive back-diffusion of acid (Li administration). Mechanisms in patients with distal renal tubular acidosis are presently unknown.