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Renal Toxicity of Lithium

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Summary

Lithium is a valuable psychotropic drug, but its therapeutic index is low. As the lithium ion is almost exclusively eliminated by the kidneys, reduced renal lithium elimination may lead to increasing serum lithium levels and lithium intoxication. Since lithium intoxication may be complicated by acute renal insufficiency, which will further delay lithium elimination, a ‘vicious circle’ can be established. Fluid therapy of any kind has been shown to have only a very limited effect on renal lithium elimination during lithium intoxication. The most efficient method for eliminating lithium from the body is through haemodialysis treatment. Peritoneal dialysis is slower but also effective. Dialysis treatment has to be carried out long enough to ensure a serum lithium concentration of less than 1mmol/L after equilibrium between intracellular and plasma lithium is established.

Lithium intoxication is often preceded by events leading to decreased fluid intake and/or increased extrarenal water and sodium loss. However, treatment with large amounts of sodium chloride should be avoided so as not to induce a condition of hypernatraemia in patients with severely impaired renal concentrating ability, which is commonly seen during and after acute lithium intoxication. Reduced renal concentrating ability is also a common complication with long term lithium treatment even without overt intoxication. As in the situation of intoxication, this condition makes the lithium-treated patient more susceptible to dehydration due to reduced fluid intake and/or increased extrarenal water and sodium loss. The reduction in renal concentrating ability is of renal, not hypothalamic, origin since plasma arginine-vasopressin concentrations are increased in patients with lithium-induced impairment of renal concentrating ability, and the hypothalamic region in these patients reacts to stimuli such as water deprivation and water loading. The impairment of renal concentrating ability is correlated to the duration of lithium treatment or to the product of serum lithium concentration and the duration of lithium treatment. The impairment of renal concentrating ability parallels histological damage to the tubules. Reduced renal concentrating ability is the most prominent lithium-induced renal lesion, since glomerular filtration rate is normal or almost normal in the majority of the patients, as is renal albumin excretion. Normal or almost normal β2-microglobulin excretion excludes any severe constant toxic action on the proximal tubules. Thus, the lithium-induced renal lesion is located in the distal part of the nephron where the highest lithium concentrations are present. Histologically, tubular lesions, cystic tubular dilatation or cysts characterise the lithium-induced nephropathy, but the origin of the fibrotic changes is still debatable, since such changes have also been found in manic-depressive patients who have not been treated with lithium.

It is unlikely that lithium-induced nephropathy will cause severe renal failure or terminal uraemia. The changes in renal function which may develop during long term lithium treatment should not result in unnecessary anxiety and do not contraindicate lithium treatment. Nevertheless, lithium therapy should be used only for severe mood disorders, and certainly lithium treatment should be efficiently controlled in order to avoid lithium intoxication, which can result in sudden deterioration in renal function, and which is the most important complication of long term lithium treatment. Patients should be warned about the dangers of dehydration, and from the initiation of treatment should drink not less than 2 to 3L of fluid per day in order to minimise lithium concentrations in the distal part of the nephron.

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    Hans Erik Hansen

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Hansen, H.E. Renal Toxicity of Lithium. Drugs 22, 461–476 (1981). https://doi.org/10.2165/00003495-198122060-00003

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