OBJECTIVE: To review the relationship between lithium-related renal dysfunction and microcysts. METHOD: Electronic databases (PubMed and Google Scholar) were queried. RESULTS: From a total of 12,425 publications, 76 were reviewed. DISCUSSION: Glomerular renal dysfunction occurs after an average of 20 years of continuous lithium treatment, and the severity is related to the total lithium load as measured by dose and duration. Recently, several reports have highlighted the relationship between renal microcyst formation and significant reductions in glomerular filtration rate. Radiologically visible lithium-related microcysts are usually 1-2 mm and occasionally 3 mm. Smaller cysts, which are impossible to resolve, are probably more common than the visible cysts, based on observations of renal needle biopsies. Increases in the number of microcysts and the space they occupy within kidney volume appear to be related to both the duration of lithium treatment and the reduction in kidney function. The proposed mechanism of microcyst formation is related to the antiapoptotic effect of lithium. Specifically, by preventing renal tubular epithelial cells from undergoing apoptosis as part of the process of normal renal maintenance, lithium may be allowing the inappropriate growth of the surface area of tubules to form invaginations and ultimately cysts. It is proposed that the physical space occupied by these cysts in the limited volume within the renal capsule compromises the function of otherwise healthy renal tissue. Monitoring of kidneys utilizing radiographic imaging may be more sensitive than monitoring laboratory values. Additional research is required to optimize this new monitoring tool.
