Chronic lithium treatment may be associated with diminution of renal concentrating ability, occasionally presenting as nephrogenic diabetes insipidus, with polyuria and polydipsia. The concentrating defect and natriuretic effect characteristic of this condition may develop within weeks of lithium initiation. Lithium can also cause renal tubular acidosis, resulting in hyperchloremic metabolic acidosis. Such patients should be carefully managed to avoid dehydration with resulting lithium retention and toxicity. This condition is usually reversible when lithium is discontinued, although for patients treated with long-term lithium, nephrogenic diabetes insipidus may be only partly reversible upon discontinuation of lithium. Amiloride may be considered as a therapeutic agent for lithium-induced nephrogenic diabetes insipidus.
Lithium can cause hyponatremia by decreasing sodium reabsorption by the renal tubules, leading to sodium depletion. Therefore, it is essential for patients receiving lithium treatment to maintain a normal diet, including salt, and an adequate fluid intake (2,500 mL to 3,000 mL) at least during the initial stabilization period. Decreased tolerance to lithium has also been reported to ensue from protracted sweating or diarrhea and, if such occur, supplemental fluid and salt should be administered under careful medical supervision and lithium intake reduced or suspended until the condition is resolved. In addition, concomitant infection with elevated temperatures may also necessitate a temporary reduction or cessation of medication.
Symptoms are also more severe with faster-onset hyponatremia. Mild hyponatremia (i.e., serum Na > 120 mEq/L) can be asymptomatic. Below this threshold, clinical signs are usually present, consisting mainly of changes in mental status, such as altered personality, lethargy, and confusion. For more severe hyponatremia (serum Na < 115 mEq/L), stupor, neuromuscular hyperexcitability, hyperreflexia, seizures, coma, and death can result. During treatment of hyponatremia, serum sodium should not be elevated by more than 10 mEq/L to 12 mEq/L in 24 hours, or 18 mEq/L in 48 hours. In the case of severe hyponatremia where severe neurologic symptoms are present, a faster infusion rate to correct serum sodium concentration may be needed. Patients rapidly treated or with serum sodium < 120 mEq/L are more at risk of developing osmotic demyelination syndrome (previously called central pontine myelinolysis). Occurrence is more common among patients with alcoholism, undernutrition, or other chronic debilitating illness. Common signs include flaccid paralysis, dysarthria. In severe cases with extended lesions patients may develop a locked-in syndrome (generalized motor paralysis). Damage often is permanent. If neurologic symptoms start to develop during treatment of hyponatremia, serum sodium correction should be suspended to mitigate the development of permanent neurologic damage.