Even Brief Lithium Exposure Can Harm

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Study highlights the importance of regular monitoring of renal function in patients taking the drug.

 

WASHINGTON, D.C.—Impaired renal function is a well-known side effect of lithium, which has been used since the 1950s to treat acute episodes of mania and as maintenance therapy for bipolar disorder. In the largest study to date of the renal effects of lithium, researchers found that the duration of lithium treatment did not correlate with glomerular filtration rate (GFR).

 

“This study confirms the importance of regular monitoring of renal function in patients taking lithium regardless of how long they have been on the drug,” said Susan Moore, MD, of St. Patrick's Hospital in Dublin, who presented findings here at the American Psychiatric Association annual meeting. “You can have impairment at any time point on lithium.”

 

She recommended monitoring renal function every six months, with a calculation of eGFR, for all patients on lithium regardless of the duration of exposure. If eGFR falls below 60, she said that patients should be referred to the nephrology department.

 

The most common form of chronic renal disease associated with lithium is a chronic tubulointerstitial nephropathy, which may lead to a reduction in GFR and a gradual rise in serum creatinine. This condition is not always reversible, even when lithium is discontinued, but it rarely progresses to end stage renal failure, she explained. Previous smaller studies have been inconclusive regarding the association of increased renal morbidity and duration of exposure to lithium, which was the impetus for the present study.

 

The retrospective study was based on computer records of 1,280 patients on lithium who had lithium levels measured while attending St. Patrick's psychiatric hospital in 2006 (both inpatients and outpatients). Forty-five percent were male. An estimated GFR above 80 mL/min per 1.73 m2 was considered normal renal function. An estimated GFR of 60-80, 30-59, and below 30 mL/min per 1.73 m2 was considered mild, moderate, and severe impairment, respectively.

 

About 26% of subjects were on lithium for as long as 18 months, whereas 11.6%, 16.6%, 18.4%, and 27.6% were on the drug for 18 months to three years, three to six years, six to nine years, and for more than 10 years, respectively.

 

Investigators observed moderate renal failure in 33.5% of those on therapy for up to 18 months; 30.2% on therapy for 18 months to three years; 34.4% on therapy for three to six years; and 49.3% on therapy for more than 10 years. Rates of severe renal impairment ranged from 0% in patients taking lithium for 0-18 months to 1.7% among those on the drug for more than 10 years, Dr. Moore said. No correlation was found for duration of exposure and eGFR. 

 

Moderate renal failure was observed in no patient younger than 20 years, 4.6% of those aged 20-29 years, 14.2% of those aged 30-44 years, 39.1% of those aged 45-59 years, 61% of those aged 60-74 years, and 80.4% of those aged 75 or older. The rate of severe renal impairment in these age groups was 0%, 0%, 0%, 0.7%, 1.7%, and 1.7%, respectively. A moderate negative association was observed between age and eGFR.

 

Study limitations include a lack of data on comorbidities and concurrent drug administration during the study period. Also, no information was provided about renal function over time.

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