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.
Short-term antimanic therapy with lithium and relapse-repressive, so-called "prophylactic" long-term therapy with lithium, may present clinical problems which demand an understanding of two cardinal properties of this form of therapy--the need to individualise the dose and the recognition that successful therapy involves the use of near-toxic dosage. Therefore, treatment must be constantly supervised, not only by the physician but also primarily by the patient himself, especially to avoid the ever-present risk of intoxication. Results of 25 years' clinical experience and more recent knowledge of the clinical pharmacokinetics of the lithium ion have shown that a serum level standardised with regard to dosage schedule, a fixed interval between last intake and blood sampling, blood sampling at the same hour, and choice of tablet brand, must all be considered essential to adjust dosage and to correctly monitor treatment. Optimum use of the lithium ion as a psychotherapeutic drug and of the standardised 12 hour lithium serum concentration, presupposes that the pharmacokinetics of the lithium ion are well understood by the clinician.
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