One lithium level >1.0 mmol/L causes an acute decline in eGFR: findings from a retrospective analysis of a monitoring database

Abstract

ObjectivesLithium is a mainstay of bipolar disorder treatment, however, there are still differences in opinion on the effects of lithium use on renal function. The aim of this analysis was to determine if there is an association between short-term exposure to various elevated lithium levels and estimated-glomerular filtration rate (eGFR) at ≤3 months, 6 months (±3 months) and 1 year (±3 months) follow-up.SettingNorfolk-wide (UK) lithium register and database.Participants699 patients from the Norfolk database.Primary outcome measureseGFR change from baseline at ≤3 months, 6 months (±3 months) and 1 year (±3 months) after exposure to a lithium level within these ranges: 0.81–1.0 mmol/L (group 2), 1.01–1.2 mmol/L (group 3) and 1.21–2.0 mmol/L (group 4). The reference group was patients whose lithium levels never exceeded 0.8 mmol/L.ResultsCompared to the reference group, groups 3 and 4 showed a significant decrease in eGFR in the first 3 months after exposure (p=0.047 and p=0.040). At 6 months (±3 months) postexposure group 4 still showed a decline in eGFR, however, this result was not significant (p=0.298).ConclusionsThese results show for the first time that a single incident of a lithium level >1.0 mmol/L is associated with a significant decrease in eGFR in the following 3 months when compared to patients whose lithium levels never exceeded 0.8 mmol/L. It is still not known whether the kidneys can recover this lost function and the impact that more than a single exposure to a level within these ranges can have on renal function. These results suggest that lithium level monitoring should be undertaken at least every 3 months, in line with current UK guidelines and not be reduced further until the impact of more than one exposure to these lithium levels has been fully established.

Long-term lithium treatment in bipolar disorder: effects on glomerular filtration rate and other metabolic parameters

“…In addition, there may be benefits in monitoring serum concentrations of lithium levels relatively frequently, especially in elderly patients. It has been suggested that lithium levels should be monitored every 3 months since even a single occurrence of a level higher than 1.0 mEq/L may result in a modest but significant decrease of the GFR lasting for at least 3 months (Bauer et al 2006 ; Van Beneden et al 2011 ; Kirkham et al 2014 ; Davis et al 2015 ; Shine et al 2015 ). In general, we would emphasize the importance of appropriate selection of patients for long-term lithium treatment, maintaining them on minimum effective doses and daily trough serum concentrations especially for older populations, and regular monitoring to assess adherence to prescribed treatment.…”

Compliance with the guidelines for laboratory monitoring of patients treated with lithium: A retrospective follow‐up study among ambulatory patients in the Netherlands

“…Adverse effects with regard to renal and thyroid function frequently occur . A significant decline in renal function has been reported in patients treated with lithium, in rare cases resulting in renal failure . Thyroid function may decline, with a risk of developing goiter.…”

Acute renal and neurotoxicity in older lithium users: How can we manage and prevent these events in patients with late-life mood disorders?

“…15 In this clinical vignette, the recent initiation of hydrochlorothiazide likely led to a cascade of events: increased lithium level, acute nephrogenic diabetes insipidus, dehydration, AKI and reduced renal clearance, leading to further lithium level increases. 6 In this case, permanent renal 4 and neurologic damage are unlikely. 2 The patient also had a history of poor psychiatric course following lithium discontinuation.…”

“…5 Consequently, lithium and renal function need monitoring every 3 months with aging. 4,5 Nephrogenic diabetes insipidus also increases toxicity risk, possibly through a feedback loop of elevated lithium levels causing acute diabetes insipidus and leading to further diuresis and lithium level elevations. 6 Other risk factors include medications commonly prescribed in late life, such as diuretics, loop diuretics, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers and nonsteroid anti-inflammatory drugs, which can increase lithium levels up to 50%.…”

“…3 Toxicity symptoms are common at levels higher than 1.5 mEq/L, although chronic lithium intoxication at levels above 0.8mEq/L may also be dangerous in older adults. 4 Natural aging also increases the risk for toxicity; the lithium dose required to achieve a given therapeutic serum level may decrease three-fold between the ages of 40 and 95 years, largely owing to decreased eGFR. 5 Consequently, lithium and renal function need monitoring every 3 months with aging.…”