The renal pathology in a case of lithium-induced diabetes insipidus

SYNOPSIS A case of lithium-induced diabetes insipidus is reported. At necropsy microscopy showed unique and extensive damage to cells lining the distal nephron. It is suggested that these changes represent a specific toxic effect of lithium, reported here for the first time in man. Lithium carbonate is widely used in psychiatric practice in the treatment of manic depressive psychosis. The toxic effects of lithium ion have been known since lithium chloride was used as a salt substitute for patients on low sodium diets 25 years ago. These are well reviewed by Schou (1968). Among the reported toxic effects is a diabetes insipidus-like state of polyuria and polydipsia (Forrest et al, 1974). Histopathological studies of the kidney in patients with this manifestation of lithium toxicity have been carried out both by renal biopsy (Schou et al, 1968) and at necropsy in fatal cases (Schou et al, 1968; Chapman and Lewis 1972). The results of these studies have been mostly nega-tive. This paper presents a case report of lithium toxicity with diabetes insipidus, showing histological evidence of unusual damage to the cells lining the distal nephron. This appears to be the first time that such changes have been described in man. Case Report A 27-year-old man had suffered from manic depres-sive psychosis for ten years. In March 1970, he was started on prophylactic treatment with lithium carbonate, initially in a dose of 1 2 g per day, rising to 2-2 g per day. Estimation of the serum lithium levels was performed at approximately monthly intervals, and at no time did the serum level exceed 1 2 mEq 1-1. Eleven months after starting lithium therapy he began to develop increasing polyuria and polydipsia, until, at the time of investigation in 1973, he was passing some 6-9 litres of urine per day. On admission to hospital physical examination revealed an obese man with a blood pressure of 170/80 mmHg. Routine investigations showe