Hans Erik Hansen

Twenty-three patients were studied, 21 of whom developed intoxication during maintenance therapy with a lithium dosage which had been unchanged for months to years. Toxic effects on brain, heart and kidneys were found and the severity of lithium intoxication seemed to depend on at least three factors: the height of the serum lithium concentration (SLi), the duration of lithium intoxication and individual tolerance. Disorders of water and electrolyte metabolism preceded lithium intoxication in the majority of the patients. Water loss due to impaired renal concentrating ability seemed to be a major predisposing factor. Renal insufficiency was apparent in 17 of the patients on admission and five of these did not regain normal renal function. In seven patients, renal biopsy showed abnormalities which suggest that a chronic nephropathy, possibly caused by lithium, might be another predisposing factor. Treatment with sodium chloride infusion had no specific effect on lithium excretion and led to hypernatraemia in some patients and is therefore not recommended. Hemodialysis is the most effective method available for removing the lithium ion from intoxicated patients. Hemodialysis should be carried out long enough to secure a SLi of less than 1 mmol/l after redistribution of lithium in the body. Treatment by peritoneal dialysis is appropriate only if hemodialysis facilities are unavailable. Lithium intoxication is a serious condition. Of the 23 patients reported, two died and two developed persisting neurological sequelae. The best way to prevent lithium intoxication is to control the serum concentration and to assess renal function and renal concentrating ability regularly during therapy.

One-hundred and ten patients treated with lithium for more than six months were studied in order to determine the prevalence of lithium induced nephropathy. Eighteen of 69 patients (26 per cent) who had been treated for more than two years presented a chronic interstitial nephropathy characterized by a marked decrease in renal concentrating ability with a disproportionate preservation of glomerular filtration rate. Histologically, increased amounts of fibrotic tissue in the medulla and the cortex were found together with tubular atrophy. In 40 per cent of the patients who underwent renal biopsy, cystic formations in the cortex were found. The impairment of renal concentrating ability could be related to the duration of lithium treatment and the degree of tubular damage correlated with the degree of impairment of renal concentrating ability. Lithium induced, chronic nephropathy is a rather common complication of long-term lithium treatment and reduces the patients capacity to regulate water and electrolyte metabolism. As water and electrolyte loss appears to precede the slowly progressing lithium intoxication, the main hazard of lithium induced nephropathy is lithium intoxication.

Kidney function has been examined in 237 patients who in the autumn of 1977 were in lithium treatment at the Psychiatric Hospital in Risskov, most of them as outpatients. The average age was 42 years. The patients had been given lithium treatment for 0.5-17 years, mean duration 5 years. The mean lithium dosage was 33 mmol/day and the mean 12-hour serum lithium concentration 0.85 mmol/l. Glomerular filtration rate was assessed through determination of 24-hour creatinine clearance and serum creatinine, in some cases iothalamate clearance. Water excretion was assessed through determination of 24-hour urine volume and in some cases urine osmolality after 26 hours of fluid deprivation. Creatinine clearances, serum creatinine concentrations, and urine volumes were subjected to multiple regression analysis with various clinically relevant predictor variables. Affection of glomerular filtration rate was only moderate and progressed slowly. The data indicate that the risk of renal insufficiency and terminal azotemia is remote even when lithium is given for many years. A large number of the patients had altered water excretion with polyuria or lowered urine concentrating ability or both. Due to the extra fluid loss these patients are apt to develop dehydration, and they may then be in danger of lithium poisoning. We hypothesize that lithium-induced changes of kidney function may become less frequent and less pronounced if patients are maintained at serum lithium levels somewhat lower than those employed in the group studied here. We recommend careful monitoring of serum lithium levels, regular control of kidney function, and extra caution when physical illness or additional drug treatment may lead to disturbance of fluid and electrolyte balance.