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Lithium induces proliferation in the epithelium of renal collecting ducts. A recent small-scale cohort study reported a strong association between use of lithium and increased risk of renal neoplasia. We therefore conducted a large-scale pharmacoepidemiologic study of the association between long-term use of lithium and risk of upper urinary tract cancer, including renal cell cancer and cancers of the renal pelvis or ureter. We identified all histologically verified upper urinary tract cancer cases in Denmark between 2000 and 2012 from the Danish Cancer Registry. A total of 6477 cases were matched by age and sex to 259,080 cancer-free controls. Data on lithium use from 1995 to 2012 were obtained from the Danish Prescription Registry. We estimated the association between long-term use of lithium (≥5 years) and risk of upper urinary tract cancer using conditional logistic regression with adjustment for potential confounders. Long-term use of lithium was observed among 0.22% of cases and 0.17% of controls. This yielded an overall nonsignificant adjusted odds ratio (OR) of 1.3 (95% confidence interval [95% CI], 0.8-2.2) for upper urinary tract cancer associated with long-term use of lithium. Analyses stratified by stage and subtype of upper urinary tract cancer revealed slight but nonsignificant increases in the ORs for localized disease (OR, 1.6; 95% CI, 0.8-3.0) and for renal pelvis/ureter cancers (OR, 1.7; 95% CI, 0.5-5.4). In conclusion, in our nationwide case-control study, use of lithium was not associated with an increased risk of upper urinary tract cancer.

Long-Term Lithium Use and Risk of Renal and Upper Urinary Tract Cancers