Lithium-induced impairment of urine acidification

Kidney Int. 1976 Apr;9(4):344-50. doi: 10.1038/ki.1976.40.


The purpose of this study was to clarify the means by which lithium induced a disorder of urine acidification. Rats infused with hydrochloric acid (1 mEq/kg) developed acute metabolic acidosis (blood Ph = 7.32; bicarbonate, 18 mEq/liter) with a urine pH of approximately 5.85. The addition of lithium chloride (4 mEq/kg i.p) caused an increase in the urine pH (6.38) and a further decrease in blood bicarbonate (11.0 mEq/liter). During bicarbonate loading, lithium caused the urine PCO2 to fall significantly (urine minus blood PCO2 decreased from 25.3 +/-2.8 To 14.4 +/- 2.3 mm Hg) These changes were not seen following equimolar i.p. administration of sodium chloride. Similarly, lithium administration depressed bicarbonate reabsorption by 11.1% (from 30.6 to 27.2muEq/ml of GFR) during alkali infusion, while saline caused only a 5% decrease (30.0 to 28.5muEq/ml of GFR). The combination of an increase in urine PCO2 in alkaline urine indicates that lithium produced a defect in distal nephron hydrogen ion secretion. The fall in bicarbonate reabsorption following lithium administration oculd be due to a mild hydrogen ion secretory defect located in the proximal tubule or a severe defect in the distal nephron.

MeSH terms

  • Acid-Base Imbalance / blood
  • Acid-Base Imbalance / chemically induced
  • Acid-Base Imbalance / urine*
  • Acidosis / urine
  • Acidosis, Renal Tubular / urine
  • Animals
  • Bicarbonates / blood
  • Bicarbonates / metabolism
  • Bicarbonates / urine
  • Glomerular Filtration Rate
  • Hydrogen-Ion Concentration
  • Kidney Tubules, Proximal / drug effects
  • Kidney Tubules, Proximal / metabolism
  • Lithium / pharmacology*
  • Male
  • Phosphates / urine
  • Rats
  • Sodium Chloride / pharmacology


  • Bicarbonates
  • Phosphates
  • Sodium Chloride
  • Lithium