Kidney Damage in Long-Term Lithium Patients: A Cross-Sectional Study of Patients with 15 Years or More on Lithium

Title: Kidney Damage in Long-Term Lithium Patients: A Cross-Sectional Study of Patients with 15 Years or More on Lithium
Authors: Bendz, H.; Aurell, Mattias; Balldin, J.; Mathe, A. A.; Sjodin, I.
Publisher: Nephrology Dialysis Transplantation
Date Published: 1994
Reference Number: 117
The renal risks associated with long-term lithium treatment are a growing concern. We have therefore studied renal function by means of glomerular filtration rate (GFR) and maximum urinary concentrating capacity (Umax) in 142 of 215 patients with more than 15 years of lithium treatment in nine psychiatric clinics. Data on psychiatric and somatic diseases, hospital admissions, cumulative lithium doses, and other psychotropic treatments were extracted from the medical records. The patients were investigated according to a standardized protocol. GFR was measured as 51Cr EDTA clearance and Umax using the DDAVP test. Thirteen patients had had signs of lithium intoxication. GFR was reduced in 21% of the patients and Umax in 44%. Nephrogenic diabetes insipidus was present in 12%. Umax but not GFR was inversely correlated to the cumulative lithium dose. Kidney function was more reduced in patients on lithium combined with psychotropic treatment and/or concomitant treatment for somatic disorders. Thirst was a complaint of 53% of the patients, predominantly those with additional psychotropics. We conclude that kidney damage is common in patients on long-term lithium treatment and that both glomerular and tubular function are affected.

This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)

Bendz, et al., studied the functional capacity of the kidneys of 142 patients with a history of long-term lithium use. The variables they examined and measured in their subjects were their glomerular filtration rate (GFR) and maximum urinary concentrating capacity (Umax). Each kidney has around one million units called nephrons that do the bulk of the work required of the kidney. The nephron consists of two parts: a glomerulus, which is a filter, and a tubule, which is a small tube. Body fluid flows through the nephron, is filtered by the glomerulus and drained by the tubule. The GFR is the quantity of glomerular filtrate (the body fluid filtered by the nephron) formed per unit of time in all nephrons of both kidneys. It is considered a good measure of kidney health.

The kidney is also able to concentrate urine and balance body water. It does this through a process mediated by the antidiuretic hormone, arginine vasopressin. Lithium, a drug often prescribed for treatment of certain psychological disorders such as manic depression, has been known to interfere with this process. Lithium can compromise the ability of the kidney to concentrate urine and thus reduce its Umax.

The authors' subject group had an average age of 61 years and averaged 19 years of lithium treatment. The patients' GFRs were measured and age adjusted. (GFR tends to become less efficient with age.) The patients' Umax was measured after abstaining from both their morning dose of lithium and water for a 12-hour period.

The patients' kidney function was found to be markedly reduced. GFR was reduced in 21% of the patients. The GFR of the other 71% was clustered in the lower limit of the normal range. Forty-four percent of the patients had reduced urinary concentrating capacity. Of those, 27% had developed nephrogenic diabetes insipidus (NDI), a kidney disorder marked by excessive thirst and excessive passage of poorly concentrated (i.e. dilute) urine.

Thus, long-term lithium treatment was associated with a decrease in GFR in one-fifth of the patients and a reduced urine concentrating capacity in nearly half the patients. This indicates that long-term lithium use does damage the kidney. Further, medical records of 73 other long-term lithium users similar to the test group in age, sex, diagnosis and lithium treatment indicated that their kidney function was also similar to the test group.

The authors noted that other studies have researched people who have been on lithium therapy for only six years. These studies indicate some detrimental effects on kidney function, but not to the extent found by the authors' study. The authors conclude that kidney damage in patients on long-term lithium treatment increases with time. They strongly advise careful monitoring of all people placed on lithium therapy.