Renal failure in lithium-treated bipolar disorder: a retrospective cohort study

PLoS One. 2014 Mar 26;9(3):e90169. doi: 10.1371/journal.pone.0090169. eCollection 2014.


Objective: Lithium users are offered routine renal monitoring but few studies have quantified the risk to renal health. The aim of this study was to assess the association between use of lithium carbonate and incidence of renal failure in patients with bipolar disorder.

Methods: This was a retrospective cohort study using the General Practice Research Database (GPRD) and a nested validation study of lithium exposure and renal failure. A cohort of 6360 participants aged over 18 years had a first recorded diagnosis of bipolar disorder between January 1, 1990 and December 31, 2007. Data were examined from electronic primary care records from 418 general practices across the UK. The primary outcome was the hazard ratio for renal failure in participants exposed to lithium carbonate as compared with non-users of lithium, adjusting for age, gender, co-morbidities, and poly-pharmacy.

Results: Ever use of lithium was associated with a hazard ratio for renal failure of 2.5 (95% confidence interval 1.6 to 4.0) adjusted for known renal risk factors. Absolute risk was age dependent, with patients of 50 years or older at particular risk of renal failure: Number Needed to Harm (NNH) was 44 (21 to 150).

Conclusions: Lithium is associated with an increased risk of renal failure, particularly among the older age group. The absolute risk of renal failure associated with lithium use remains small.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Bipolar Disorder / drug therapy*
  • Female
  • Humans
  • Lithium / adverse effects*
  • Lithium / therapeutic use*
  • Male
  • Middle Aged
  • Models, Biological
  • Proportional Hazards Models
  • Renal Insufficiency / chemically induced*
  • Reproducibility of Results
  • Retrospective Studies
  • Risk Factors
  • Survival Analysis
  • Treatment Outcome
  • Withholding Treatment
  • Young Adult


  • Lithium

Grants and funding

An unrestricted academic grant from the British Renal Society (grant no. 07/010). All authors are independent from the funding body. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.