Lithium may increase risk for renal decline among older adults

Lithium use among older adults was associated with increased risk for renal decline, according to results of a population-based cohort study published in Journal of Clinical Psychiatry.

“Recent large epidemiologic studies including both geriatric and adult patients have reported a 1.5- to 2.5-fold higher risk [for] incident [chronic kidney disease] among lithium users,” Soham Rej, MD, MSc, of the department of psychiatry at McGill University in Canada, and colleagues wrote. “Fears of increased renal disease have contributed to the low North American rates of prescribing lithium in bipolar disorder: [less than] 8% to 15% vs. 30% to 50% in parts of Europe. However, the link between lithium and a long-term decline in kidney function remains somewhat controversial, particularly in younger adult patients, with some studies finding no association.”

Prior studies in this area tended to have limited geriatric sample sizes of fewer than 50 to 100 participants. Further, extrapolating study findings related to younger adults did not prove feasible, since older adults were more likely to have premorbid renal decline, multiple cardiovascular comorbidities and concurrent pharmacotherapies that could affect risk.

In the current study, Rej and colleagues sought to determine whether lithium use was associated with increased risk for renal decline compared with valproate and whether this association varied with higher vs. lower baseline serum lithium concentrations. They used linked health care databases from Ontario, Canada, to analyze 2007 to 2015 data of older adults with a mean age of 71 years. They propensity-score matched 3,113 lithium users 1:1 to 3,113 valproate users and further examined those with higher or lower concentrations of serum lithium. A 30% or greater loss in estimated glomerular filtration rate from baseline served as the primary outcome.

Results showed similar baseline health indicators over a median follow-up of 3.1 years between lithium and valproate users. The researchers reported an association between lithium and increased risk for renal function loss compared with valproate, with 6.5 vs. 5.7 events per 100 person years for the former vs. the latter (hazard ratio = 1.14; 95% CI, 1.02-1.27). The risk for renal decline when baseline serum lithium concentrations were greater than 0.7 mmol/L was 1.26 (95% CI, 1.06-1.49) compared to valproate use, and this risk was 1.06 (95% CI, 0.92-1.22) when baseline lithium concentrations were 0.7 mmol/L or fewer.

“An interesting future direction, if ever feasible in an even larger older lithium user sample, could be the following: to use a receiver operating curve analysis to identify the serum lithium level at which CKD risk begins to elevate,” Rej and colleagues wrote. “Further research could also assess whether changing laboratory recommendations for geriatric lithium levels to [less than or equal to] 0.7 mmol/L and the use of centralized monitoring/warning systems could still be effective psychiatrically, while preventing renal disease in lithium users.”