Mechanisms of renal lithium handling and their relationship to mineralocoticoids: A dissociation between sodium and lithium ions

• Published in: Journal of psychiatric research Vol. 8; no. 2; pp. 91 - 105
• Main Authors: Baer, Leslie, Platman, Stanley R., Kassir, Suham, Fieve, Ronald R.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 1971
• ISSN: 0022-3956; 1879-1379
• DOI: 10.1016/0022-3956(71)90011-2

Lithium-induced alterations in electrolyte excretion were studied in 16 patients with manic-depressive disease and in one normal subject under conditions of controlled sodium, potassium and fluid intake. An increase in urinary sodium and potassium excretion and in urine volume were noted on the first day of lithium administration. By lithium day 3, transient sodium retention occured. These changes in electrolyte excretion were not correlated with measurable changes in endogenous creatinine clearance. Sodium loading diminished and sodium depletion increased lithium retention. While sodium depletion always raised serum lithium levels, in one patient signs of lithium toxicity appeared despite relatively low serum lithium concentrations. These observations suggest that serum lithium may not be an accurate indicator of lithium overdose, especially during states of acute sodium depletion. Chlorothiazide and the aldosterone antagonist spironolactone produced a striking sodium diuresis, but lithium excretion did not increase consistently and at times decreased. Differences in renal sodium and lithium handling were also observed in response to desoxycorticosterone acetate (DOCA) administration. In rats, DOCA failed to cause lithium retention despite prompt retention of sodium. During the DOCA ‘escape’ period, lithium excretion increased and serum lithium concentration fell. Thus, renal lithium handling, unlike sodium handling, appears independent of mineralocorticoids. These characteristics of lithium excretion during DOCA administration in rats and aldosterone blockade in man suggest that the proximal tubule is the major site of lithium reabsorption in these species. These in vivo studies in man and animals indicate a decreased capacity of active transport systems in the kidney to handle the lithium ion as effectively as the sodium ion. These differences in sodium and lithium handling by the kidney may be related, in part, to lithium's mechanism of action, particularly if active transport systems in the central nervous system are qualitatively similar to those of the kidney with respect to lithium handling.