Predictors of severe kidney disease in long-term lithium treatment

Abstract

The thesis aims to advance the understanding of severe chronic kidney disease in lithium-treated patients through four observational studies in which subjects were recruited from the Sahlgrenska University Hospital laboratory database. The findings of Paper I revealed a gradual increase in adherence to lithium monitoring guidelines over 30 years, with mean lithium levels decreasing over time, within the recommended range. Paper II showed an almost sevenfold increased risk of severe chronic kidney disease in patients with moderately elevated serum creatinine, indicating pre-existent renal damage, prior to lithium initiation, compared to matched controls. Paper III indicated that a low (1%) risk of severe chronic kidney disease during the first ten years of lithium treatment remained unchanged over a time span of three decades. Paper IV highlighted age-dependent variations in the lifetime risk of severe chronic kidney disease, with the highest risk in patients starting lithium at age 65-74 years. Patients below 55 years of age at lithium start had negligible 10-year risk. Prolonged lithium exposure, especially over 20 years, was a significant risk factor. The findings corroborate the notion that lithium treatment per se poses a certain risk of severe chronic kidney disease. While pretreatment renal impairment markedly elevates the risk, a normal serum creatinine level is associated with moderate excess risk and should not preclude lithium use in patients who could benefit from it. Key predictors of severe renal impairment include age, baseline creatinine and duration of lithium exposure, with no significant influence of sex.