title: Use of Lithium and Anticonvulsants and the Rate of Chronic Kidney Disease: A Nationwide Population-Based Study.
abstract: OBJECTIVE
  Lithium is the main mood stabilizing drug for bipolar disorder. However, it is controversial whether long-term maintenance treatment with lithium or other drugs for bipolar disorder causes chronic kidney disease (CKD).
  
  
  OBJECTIVE
  To compare rates of CKD and in particular rates of end-stage CKD among individuals exposed to successive prescriptions of lithium, anticonvulsants, or other drugs used for bipolar disorder.
  
  
  METHODS
  This is a Danish nationwide population-based study of 2 cohorts. Cohort 1 comprised a randomly selected sample of 1.5 million individuals among all persons who were registered in Denmark on January 1, 1995, all patients with a diagnosis of a single manic episode or bipolar disorder between January 1, 1994, and December 31, 2012 (n =10,591), and all patients exposed to either lithium (n = 26,731) or anticonvulsants (n=420,959). Cohort 2 included the subgroup of 10,591 patients diagnosed as having bipolar disorder.
  
  
  METHODS
  Possible CKD, definite CKD, and end-stage CKD (defined as long-term dialysis or renal transplantation).
  
  
  RESULTS
  A total of 14,727 (0.8%), 18,762 (1.0%), and 3407 (0.2%) in cohort 1 and 278 (2.6%), 319 (3.0%), and 62 (0.6%) in cohort 2 were diagnosed as having possible, definite, or end-stage CKD, respectively. Based on the total sample and not considering diagnoses, use of lithium was associated with an increased rate of definite CKD (0 prescriptions: hazard ratio [HR] = 1.09, 95% CI, 0.81-1.45; ≥60 prescriptions: HR = 3.65, 95% CI, 2.64-5.05; P for trend < .001) and possible CKD (0 prescriptions: HR = 1.01, 95% CI, 0.79-1.30; ≥60 prescriptions: HR = 2.88, 95% CI, 2.17-3.81; P for trend < .001), whereas use of anticonvulsants, antipsychotics, or antidepressants was not. Neither use of lithium nor use of any other drug class was associated with increasing rates of end-stage CKD. In patients with bipolar disorder, use of lithium was associated with an increased rate of definite CKD (1-2 prescriptions: HR = 0.89, 95% CI, 0.39-2.06; ≥60 prescriptions: HR = 2.54, 95% CI, 1.81-3.57; P for trend < .001) or possible CKD (1-2 prescriptions: HR = 1.26, 95% CI, 0.65-2.43; ≥60 prescriptions, HR = 2.48, 95% CI, 1.80-3.42; P for trend < .001), as was use of anticonvulsants (definite CKD, 1-2 prescriptions: HR = 1.23, 95% CI, 0.76-1.99; ≥60 prescriptions, HR = 2.30, 95% CI, 1.53-3.44; P for trend < .001; possible CKD, 1-2 prescriptions: HR = 1.11, 95% CI, 0.70-1.76; ≥60 prescriptions: HR = 1.97, 95% CI, 1.34-2.90; P for trend < .001). There was no such association with antipsychotics or antidepressants. Also in patients with bipolar disorder, use of lithium was not significantly associated with an increased rate of end-stage CKD, whereas use of anticonvulsants was (1-2 prescriptions, HR = 0 [95% CI, 0.00-infinity]; 30-39 prescriptions: HR = 3.23, 95% CI, 1.26-8.27; ≥60 prescriptions: HR = 2.06, 95% CI, 0.82-5.16; P for trend = .002).
  
  
  CONCLUSIONS
  Maintenance treatment with lithium or anticonvulsants as practiced in modern care is associated with an increased rate of CKD. However, use of lithium is not associated with an increased rate of end-stage CKD. The associations between use of medication and CKD may at least partly be attributed to bias.
authors.affiliation: Psychiatric Center Copenhagen, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Lars Vedel
authors.initials: LV
authors.lastname: Kessing
authors.affiliation: Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Thomas Alexander
authors.initials: TA
authors.lastname: Gerds
authors.affiliation: Department of Nephrology, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark4Department of Psychiatry, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Bo
authors.initials: B
authors.lastname: Feldt-Rasmussen
authors.affiliation: Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Per Kragh
authors.initials: PK
authors.lastname: Andersen
authors.affiliation: Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
authors.forename: Rasmus W
authors.initials: RW
authors.lastname: Licht
mesh_terms: D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000009:adverse effects*; D000928:Antidepressive Agents / Q000009:adverse effects; D014150:Antipsychotic Agents / Q000009:adverse effects; D001714:Bipolar Disorder / Q000188:drug therapy; D003718:Denmark / Q000453:epidemiology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000139:chemically induced / Q000453:epidemiology; D008094:Lithium / Q000009:adverse effects*; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000139:chemically induced* / Q000453:epidemiology*
chemical_list: D000927:Anticonvulsants; D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D008094:Lithium