Use of Lithium and Anticonvulsants and the Rate of Chronic Kidney Disease
Authors: Lars Vedel Kessing, Thomas Alexander Gerds, Bo Feldt-Rasmussen, Per Kragh Andersen, Rasmus W. Licht
Journal: JAMA Psychiatry (2015)

IMPORTANCE 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.DESIGN, SETTING, AND PARTICIPANTS 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. MAIN OUTCOMES AND MEASURES 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;Ն60 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;Ն60 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;Ն60 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;Ն60 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;Ն60 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;Ն60 prescriptions: HR = 1.97, 95% CI, 1.34-2.90;P for trend < .001).There was no such associationwithantipsychoticsorantidepressants.Alsoinpatientswithbipolardisorder,useoflithium was not significantly associated with an increased rate of end-stage CKD, whereas use of anticonvulsantswas(1-2prescriptions,HR = 0[95%CI,0.00-infinity];30-39prescriptions:HR= 3.23, 95% CI, 1.26-8.27;Ն60 prescriptions: HR = 2.06, 95% CI, 0.82-5.16;P for trend = .002).CONCLUSIONS AND RELEVANCE 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.