• Filip Fransson, Ursula Werneke, Louise Öhlund, P Andreas Jonsson, and Michael Ott.
• Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
• J. Intern. Med. 2025 Jan 20.

BackgroundLong-term lithium treatment decreases kidney function. However, it remains unclear whether stopping lithium improves kidney function.ObjectivesTo study kidney function in patients who stopped and subsequently restarted lithium treatment.MethodsMirror-image design using data from the LiSIE retrospective cohort study. The mirror was set to when lithium was stopped with a 5-year pre- and post-mirror period. Adult patients with bipolar, schizoaffective disorder or unipolar depression, who had lithium ≥4.5 years in the pre-mirror period, were included. Creatinine measurements were available from 1997 to 2017. The main outcome was the difference in mean annual change of the estimated glomerular filtration rate (eGFR) adjusted for sex, hypertension and diabetes mellitus.ResultsA total of 168 participants (94 women, 74 men) were included. Mean annual eGFR change was -1.58 (-1.87 to -1.28) mL/min/1.73 m2/year before and -0.023 (-0.49 to +0.44) mL/min/1.73 m2/year after lithium discontinuation (p < 0.0001 for difference). The improvement was 0.77 (0.35-1.20) mL/min/173 m2/year in participants with eGFR >60 mL/min/1.73 m2, and 3.03 (2.15-3.92) mL/min/1.73 m2/year for participants with eGFR <30 mL/min/1.73 m2. The effect was persistent over the 5-year post-mirror study period. For participants restarting lithium, the mean annual eGFR change was -1.71 (-2.26 to -1.16) mL/min/1.73 m2/year, a setback compared to their lithium-free post-mirror period (p < 0.0001). We did not see any difference compared to the pre-mirror period (p = 0.51).ConclusionsStopping lithium slowed down mean eGFR decline. This effect was more pronounced in participants with lower eGFR at the time of lithium discontinuation. In participants who restarted lithium, the annual decline of eGFR reverted to pre-lithium discontinuation levels.© 2025 The Author(s). Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

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