Long-term lithium exposure does not increase renal dysfunction risk

By Lucy Piper, Senior medwireNews Reporter

Stable lithium maintenance therapy does not increase the risk of renal dysfunction in patients with bipolar affective disorder, findings from a population-based study suggest.

The results refute those of previous studies citing duration of lithium treatment and cumulative dose as the major causative factors for nephrotoxicity, which the researchers say were affected by inappropriate study design.

Indeed, they found that the main determinants of renal dysfunction among patients taking lithium were baseline estimated glomerular filtration rate (eGFR), age, comorbidities such as diabetes and hypertension, prescriptions of nephrotoxic drugs, and episodes of lithium toxicity (levels above 0.8 mmol/L), not duration of lithium exposure nor average lithium dose.

“[T]he findings from this study should be taken into account by physicians when they are considering discontinuation of maintenance therapy because of assumed chronic lithium toxicity in the absence of episodes of acute toxicity”, comment researcher Stefan Clos (Murray Royal Hospital, Perth, UK) and colleagues.

The team identified 1120 patients from the Health Informatics Centre prescribing database, 41% of whom had an ICD-10 mood disorder diagnosis. Of these, 305 had at least 6 months’ exposure to lithium and 815 to a comparator drug (quetiapine, olanzapine or semisodium valproate). None of the patients had prior exposure to lithium or the comparator drugs, a history of psychosis or previous kidney disease.

The average duration of lithium exposure was 55 months and the average serum lithium level was 0.56 mmol/L, ranging from 0.24 to 1.0 mmol/L, and 91% of recorded lithium levels did not exceed 0.8 mmol/L.

Based on assessment of a total 13,963 eGFR measurements over a maximum follow-up of 12 years, the average annual decline in eGFR among patients taking lithium was 1.3 mL/min per 1.73 m² after taking into account age, gender and baseline eGFR, and 1.0 mL/min per 1.73 m² after further adjustment for comorbidities, co-prescriptions and episodes of lithium toxicity.

These rates did not differ significantly from those of patients taking comparator drugs, at a respective 0.9 mL/min per 1.73 m² and 0.4 mL/min per 1.73 m², and were within the normal range according to The National Institute for Health and Care Excellence (NICE) guidelines for chronic kidney disease.

The researchers estimate that the monthly decline in eGFR attributable to lithium exposure was just 0.02 mL/min per 1.73 m².

“Our data strongly support the view that stable lithium maintenance therapy does not increase the risk of renal dysfunction in adult populations with affective disorder”, the team comments in TheLancet Psychiatry.

They note, however, that the present cohort was primarily White, and so are hesitant about extrapolating the recommendations to patients of other ethnic origins.

They conclude that, in line with the 2008 NICE guidelines, the focus for patients with incidental chronic kidney disease before or during lithium treatment should still be active management of comorbidities such as diabetes and hypertension and other cardiovascular risk factors and avoidance of acute lithium toxicity.

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