Effects of Lithium Treatment on Renal Function in Bipolar Disorder: A Retrospective Cohort Study

Lithium remains a cornerstone treatment for bipolar disorder, but concerns about its long-term renal safety persist. This study examined clinical and lithium-related predictors of eGFR decline in patients receiving long-term lithium therapy.

In this retrospective cohort study, 636 patients with bipolar disorder treated with lithium for at least one year at a single psychiatric clinic (2010-2022) were evaluated. Estimated glomerular filtration rate (eGFR) was calculated at baseline, an intermediate time point, and the last follow-up using the CKD-EPI 2021 equation. The primary outcome was a decline of 25% or more in eGFR from baseline. Logistic regression, multiple linear regression, and linear mixed-effects models were used to identify independent predictors of eGFR decline.

A ≥25% decline in eGFR occurred in 87 patients (13.7%). Older age (OR=1.05) and a history of supratherapeutic lithium levels (OR=1.66) were independently associated with decline; when mean lithium level was modeled continuously, higher levels were also associated with decline (OR=1.51 per 0.1 mmol/L). In the mixed-effects model, older age and female sex were associated with lower eGFR, whereas lithium treatment duration was not independently associated with renal outcomes in any model.

The retrospective, single-center design limits causal inference and generalizability, and eGFR was estimated rather than directly measured.

Renal function decline was associated with older age and higher lithium exposure (a history of supratherapeutic levels and higher mean levels), but not with treatment duration. Regular monitoring and prevention of supratherapeutic lithium exposure may help minimize renal risk during long-term lithium therapy.