Key PointsQuestionHow is lithium therapy, compared with valproate therapy, associated with kidney outcomes?FindingsIn this cohort study of 10 946 patients followed up for up to 10 years in Sweden, no significant differences in relative and absolute risk of chronic kidney disease progression, albuminuria, or acute kidney injury (AKI) were found among patients who received lithium compared with those who received valproate. However, high levels of lithium were strongly associated with AKI risks.MeaningInitiation of lithium therapy was not associated with risk of chronic kidney disease, albuminuria, or AKI, but the association between higher lithium levels and AKI calls for continuous patient monitoring and lithium dose adjustment to avoid toxic levels.