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530 www.psychopharmacology.com current evidence is sufficient to conclude that long-term use (>10 years) of lithium may inducemicrocysts, oncocytomas, and collecting duct renal carcinomas. Thereupon, marketing authorization holders of lithium containing medical products were requested to amend the product information accordingly. The currently available epidemiological studies regarding the association between lithium therapy (LT) and renal and urinary tract tumors, however, differ significantly in terms of included tumors, methodology, and results. Thus, an adequate evaluation of the relation between (long-term) LT and the risk for renal und urinary tract tumors is currently not possible. The mechanisms underlying lithiuminduced nephrotoxicity in general and lithium-associated oncogenesis in the kidney and the upper and lower urinary tract in particular are not completely understood. Lithium exerts possible oncogenic effects merely in the intracellular space and primarily enters the cells of the kidney via the amiloride-sensitive epithelial sodium channel (ENaC). The urothelium of renal pelvis, ureter, bladder, and urethra also expresses ENaCs, thus making these tissues theoretically also susceptible to lithium-associated oncogenesis. However, the aforementioned epidemiological studies have not considered the lower urinary tract (urethra and bladder). In addition, the ENaC consists of 3 different subunits (α, β, γ) and a fourth so-called δ subunit, whose function is unknown. These subunits are expressed differently in kidneys and the urothelium of renal pelvis, ureter, bladder, and urethra (eg, stronger expression of α, β, and γ subunits in the kidney than in the urothelium of the bladder). Therefore, there may be a relation between the tissue-specific expression of ENaCs and the tissue-specific susceptibility regarding lithium-associated oncogenesis. Taking into account these aspects, we performed an exploratory retrospective, single-center analysis of patients with malignant and benign renal and upper and lower urinary tract tumors to (1) determine the prevalence of LT and (2) investigate if the prevalence of LT varies significantly between different tumor entities as an indication of a possible relation between the tissue-specific susceptibility regarding lithium-associated oncogenesis and the tissue-specific expression of ENaCs. The study protocol was introduced to the local ethics committee/human subjects committee of Ulm University and received approval. All patients receiving treatment in the Department of Urology at the University Hospital of Ulm between January 1, 2006, and December 31, 2015, owing to 1 or more of the following index tumor

Lithium Therapy Associated With Renal and Upper and Lower Urinary Tract Tumors