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Lithium maintenance does not increase risk for renal dysfunction

Recent findings indicate stable lithium maintenance does not increase risk for renal dysfunction among adults with bipolar affective disorder.

“Lithium remains a key drug in the maintenance therapy of bipolar affective disorder, but has a narrow therapeutic index and requires regular monitoring of serum levels and renal function, as it is nearly exclusively excreted over the kidneys,” Stefan Clos, MSc, PhD, of Murray Royal Hospital, Perth, United Kingdom, and colleagues wrote. “Subsequently it has been speculated whether there is a specific lithium nephropathy or glomerular disease leading to renal insufficiency or end-stage renal disease.”

To analyze the effect of lithium maintenance therapy on estimated glomerular filtration rate among individuals with affective disorders, researchers compared individuals who recently started lithium maintenance treatment (n = 305) with those exposed to other first-line drugs used to treat affective disorders (n = 815), such as quetiapine, olanzapine and semisodium valproate between January 2000 and December 2011. Study participants had at least 6 months of exposure to lithium or any of the comparator drugs. Maximum follow-up was 12 years.

Mean duration of exposure to lithium was 55 months.

Mean annual decline in estimated glomerular filtration rate was 1.3 mL/min per 1.73 m² among individuals exposed to lithium and 0.9 mL/min per 1.73 m² among those exposed to comparator drugs, when adjusting for age, sex and baseline estimated glomerular filtration rate.

After adjusting for additional cofounders, monthly decline in estimated glomerular filtration rate related to lithium exposure was 0.02 mL/min per 1.73 m² (P = .3).

Researchers estimated an annual decline in estimated glomerular filtration rate of 1 mL/min per 1.73 m² for those exposed to lithium and 0.4 mL/min per 1.73 m² for those exposed to comparator drugs.

Age, baseline estimated glomerular filtration rate, comorbidities, co-prescriptions of nephrotoxic drugs and episodes of lithium toxicity were significant predictors of decline in estimated glomerular filtration rate.

“Our data strongly support the view that stable lithium maintenance does not increase the risk [for] renal dysfunction in adult affective disorder patients. We identified predictors for a decline in [estimated glomerular filtration rate] to baseline [estimated glomerular filtration rate], age, comorbidities, co-prescriptions of nephrotoxic drugs and episodes of lithium toxicity, but not length of lithium exposure or mean lithium serum level,” the researchers wrote. “The present findings should be taken into account when considering discontinuation of maintenance therapy due to assumed ‘chronic lithium toxicity in the absence of episodes of acute toxicity.” – by Amanda Oldt

Disclosure: Please see the full study for a list of all authors’ relevant financial disclosures.