title: On the mechanism of lithium-induced renal tubular acidosis.
abstract: The effect of lithium chloride administration on urinary acidification was studied in dogs. Lithium-treated dogs developed hyperchloremic metabolic acidosis with alkaline urine. Bicarbonate loading resulted in a normal increase in urinary Pco2 in normal dogs but failed to produce the same response in lithium-treated dogs. The bicarbonate titration curve of lithium-treated dogs revealed a small leak of bicarbonate at low plasma levels of bicarbonate; at high plasma levels bicarbonate reabsorption was significantly higher in lithium-treated dogs. This pattern of bicarbonate reabsorption is identical to that described in classic distal renal tubular acidosis. Sodium sulfate administration resulted in a normal urinary acidification ilithium-treated dogs. It is possible that lithium administration induces distal renal tubular acidosis by allowing excessive back-diffusion of acid. This excessive back-diffusion of acid would result in a low urinary Pco2 during bicarbonate loading. Sodium sulfate administration, by increasing the negative intratubular potential, would restrict back-diffusion of hydrogen ion and thereby result in a normal acidification in lithium-treated dogs. We previously demonstrated that postureteral obstruction of the kidney fails to increase urinary Pco2 during bicarbonate loading and to lower urinary pH with sodium sulfate. It is possible that a low urinary Pco2 during HCO3 loading can occur as a consequence of either diminished hydrogen ion secretion (postobstructed kidney) or excessive back-diffusion of acid (lithium administration). Further studies are indicated to determine whether both mechanisms may be found in patients with distal renal tubular acidosis.
mesh_terms: D000042:Absorption; D000141:Acidosis, Renal Tubular / Q000139:chemically induced / Q000503:physiopathology* / Q000652:urine; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D002245:Carbon Dioxide / Q000652:urine; D004285:Dogs; D005260:Female; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology*; D008094:Lithium; D011188:Potassium / Q000652:urine
chemical_list: D001639:Bicarbonates; D002245:Carbon Dioxide; D008094:Lithium; D011188:Potassium