A large, nationwide Danish study finds no association between long-term lithium use and the risks of upper urinary tract cancers.
Previously, a small-scale study had found a strong link between lithium, a medication commonly used to treat bipolar affective disorders, and genitourinary cancers. Preliminary animal and human studies had also raised the possibility that lithium’s nephrotoxic effects extended to malignancy.
In Denmark, medical care is nationalized, allowing for comprehensive data capture on a population level. For the current study, investigators led by Anton Pottegard, PhD, a clinical pharmacist at the University of Southern Denmark, identified 6,477 histologically-verified upper urinary tract cancers cases from the Danish Cancer Registry between 2000 and 2012. The cancers included a first-time diagnosis of invasive cancer of the kidney, renal pelvis, or ureter. Cases were then matched by age and sex to 259,080 controls. Based on the Danish Prescription Registry, less than a quarter percent of cases and controls were taking lithium for at least 5 years.
According to findings published online ahead of print in the Journal of the American Society of Nephrology, long-term use of lithium was linked to a non-significant 30% increased odds of the cancers. Even in the worst case scenario, researchers estimated that it would take 3,091 person-years of lithium exposure to see 1 additional cancer case. Analyses by cancer stage and subtype also revealed only slight, non-significant increased odds. Results were adjusted for other drugs, diseases, and socioeconomic factors believed to affect the kidney.
“In conclusion, we can exclude any major effect of long-term lithium use on the risk of renal cancer or cancers of the renal pelvis or ureter,” the investigators wrote. “Although long-term lithium use may be associated with other renal adverse effects, it is reassuring that lithium use does not appear to induce renal cancer, and that lithium can be kept on the armamentarium for conditions as debilitating as bipolar disorder and severe unipolar depression.”
The researchers noted that their findings might be affected by surveillance bias, “as lithium users frequently undergo renal function tests and generally have more frequent contact with the health care system compared with individuals without bipolar disorder or severe depression, and no lithium use.”