Use of Lithium and Anticonvulsants and the Rate of Chronic Kidney Disease: A Nationwide Population-Based Study
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Use of Lithium and Anticonvulsants and the Rate of Chronic Kidney Disease : A Nationwide Population-Based Study. / Kessing, Lars Vedel; Gerds, Thomas Alexander; Feldt-Rasmussen, Bo; Andersen, Per Kragh; Licht, Rasmus W.
I: J A M A Psychiatry, Bind 72, Nr. 12, 12.2015, s. 1182-91.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Use of Lithium and Anticonvulsants and the Rate of Chronic Kidney Disease
T2 - A Nationwide Population-Based Study
AU - Kessing, Lars Vedel
AU - Gerds, Thomas Alexander
AU - Feldt-Rasmussen, Bo
AU - Andersen, Per Kragh
AU - Licht, Rasmus W
N1 - Error in Author Affiliations JAMA Psychiatry. 2016;73(2):179. doi:10.1001/jamapsychiatry.2015.3326
PY - 2015/12
Y1 - 2015/12
N2 - 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; ≥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 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.
AB - 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; ≥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 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.
U2 - 10.1001/jamapsychiatry.2015.1834
DO - 10.1001/jamapsychiatry.2015.1834
M3 - Journal article
C2 - 26535805
VL - 72
SP - 1182
EP - 1191
JO - JAMA Psychiatry
JF - JAMA Psychiatry
SN - 2168-622X
IS - 12
ER -
ID: 157490841