Lithium and renal and upper urinary tract tumors - results from a nationwide population-based study

Bipolar Disord. 2015 Dec;17(8):805-13. doi: 10.1111/bdi.12344. Epub 2015 Nov 3.

Abstract

Objectives: A recent alarming finding suggested an increased risk of renal tumors among long-term lithium users. The objectives of the present study were to estimate rates of renal and upper urinary tract tumors (RUT), malignant and benign, among individuals exposed to successive prescriptions for lithium, anticonvulsants, and other psychotropic agents used for bipolar disorder, and among unexposed individuals.

Methods: This was a nationwide, population-based longitudinal study including time-specific data from all individuals exposed to lithium (n = 24,272) or anticonvulsants (n = 386,255), all individuals with a diagnosis of bipolar disorder (n = 9,651), and a randomly selected sample of 1,500,000 from the Danish population. The study period was from 1995 to 2012, inclusive. Outcomes were hazard rate ratios (HR) for RUT in three groups: (i) combined malignant and benign, (ii) malignant, and (iii) benign. Analyses were adjusted for the number of prescriptions for lithium/anticonvulsants, antipsychotic agents, antidepressants, and use of all other types of medication; age; gender; employment status; calendar year; and a diagnosis of bipolar disorder.

Results: Continued treatment with lithium was not associated with increased rates of RUT [adjusted HR malignant or benign: 0.67-1.18, p (trend) = 0.70; adjusted HR malignant: 0.61-1.34, p (trend) = 0.90; adjusted HR benign: 0.74-1.18, p (trend) = 0.70]. Similarly, continued treatment with anticonvulsants was not associated with increased rates of RUT [adjusted HR malignant or benign: 0.97-1.18, p (trend) = 0.10; adjusted HR malignant: 0.82-1.15, p (trend) = 0.80; adjusted HR benign: 0.94-1.36, p (trend) = 0.20]. The associations were confirmed among the 9,651 patients with a diagnosis of bipolar disorder.

Conclusions: Treatment with lithium is not associated with increased rates of RUT.

Keywords: bipolar disorder; lithium; renal and upper urinary tract cancer; renal and upper urinary tract tumors; renal tumor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anticonvulsants* / administration & dosage
  • Anticonvulsants* / adverse effects
  • Anticonvulsants* / therapeutic use
  • Bipolar Disorder* / diagnosis
  • Bipolar Disorder* / drug therapy
  • Bipolar Disorder* / epidemiology
  • Denmark / epidemiology
  • Female
  • Humans
  • Incidence
  • Lithium Compounds* / administration & dosage
  • Lithium Compounds* / adverse effects
  • Long Term Adverse Effects* / chemically induced
  • Long Term Adverse Effects* / diagnosis
  • Long Term Adverse Effects* / epidemiology
  • Long Term Adverse Effects* / pathology
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care
  • Proportional Hazards Models
  • Psychotropic Drugs* / administration & dosage
  • Psychotropic Drugs* / adverse effects
  • Psychotropic Drugs* / classification
  • Risk Factors
  • Socioeconomic Factors
  • Urologic Neoplasms* / classification
  • Urologic Neoplasms* / epidemiology
  • Urologic Neoplasms* / etiology
  • Urologic Neoplasms* / pathology

Substances

  • Anticonvulsants
  • Lithium Compounds
  • Psychotropic Drugs