The Effect of Sodium Chloride on Kidney Function in Rats with Lithium Intoxication

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Abstract
The effect of lithium was studied in 3 groups of rats given food containing 20, 40, or 60 mmol LiCl/kg dry weight for 3‐4 weeks. The animals had free access to demineralized water. The mean serum lithium levels after 3 days were 0.4, 0.7, and 1.1 mM, respectively. The rats with low and medium lithium intakes could be maintained at this level for a very long time. In the rats with a high lithium intake the serum lithium concentration after 2‐3 weeks rose to high values as a result of a decrease in the renal lithium clearance; the rats developed severe lithium intoxication. Replacement of demineralized water with 80 mM NaCl solution in severely intoxicated rats reversed the toxic effects; the lithium clearance rose, and the serum lithium returned to the same level as observed before the intoxication. Administration from the start of the experiment of 20 mM NaCl as the only drinking fluid prevented the development of severe intoxication even in rats given food with 100 mmol LiCl/kg dry weight. No decrease in the lithium clearance occurred during an observation period of 8 weeks, and the serum lithium concentration remained constant with a mean value of 1.4 mM. The results indicate that the decrease in lithium clearance produced by prolonged administration of high lithium doses is not due to irreversible kidney damage; it can be reversed by the administration of sodium. The development of severe intoxication can also be prevented by administering sodium along with lithium. These observations support the hypothesis that sodium depletion plays an important role in the development of severe lithium intoxication.

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