Lithium nephrotoxicity: a systematic review and meta-analysis of lithium versus non-lithium control studies in patients with affective disorders

Abstract

Background: Lithium, the gold standard treatment of bipolar disorder (BD), is thought to cause nephropathy in long-term users. However, the role of confounding variables linked to BD in exerting this adverse effect remains unclear. Objectives: This paper evaluates kidney function in patients with affective disorders who are taking lithium compared to patients not on lithium treatment. Design: This article is a systematic review and meta-analysis. Data sources and methods: A comprehensive search of publications up to October 2023 within Cochrane, Embase, PubMed, Scopus, Web of Science, and CINAHL databases was performed. Three assessors screened and extracted data from eligible observational studies. Risk of bias assessment was done with the ROBINS-E tool. Eligible studies were comparative studies of adult patients with diagnoses of affective disorders, including BD on lithium, with control groups not on lithium, reporting kidney function outcomes. Results: Mean estimated Glomerular filtration rate (eGFR) showed less favorable outcomes in the lithium group compared to the non-lithium group (n = 1622, MD = −11.14 ml/min/1.73 m2, 95% CI: −16.61, −5.68, I2 = 86%). The mean annual eGFR decline comparison favored the non-lithium group (n = 13,280, MD = 0.13 ml/min/1.73 m2, 95% CI: 0.06, 0.20,I2 = 0%). Serum creatinine concentration (mg/dl) was found to be higher in the lithium compared to non-lithium groups (n = = 1704, MD = 0.05, 95% CI: 0.03, 0.07,I2 = 3%). New or progressing chronic kidney disease events were not found to be statistically different between the lithium and control groups (n = = 17,740, OR = 2.16, 95% CI: 0.59, 7.94,I2 = 99%). The high heterogeneity in this meta-analysis limits the reliability and interpretability of our results. Conclusion: Kidney function, as measured by eGFR, was decreased in the lithium-taking groups versus the non-lithium groups. Continuous monitoring and discussion of risks and benefits with patients, especially those with a baseline of reduced kidney function, is imperative. Trial registration: This review was registered prospectively with PROSPERO (CRD42024517414).