Use of Lithium and Anticonvulsants and the Rate of Chronic Kidney Disease: A Nationwide Population-Based Study

Lars Vedel Kessing; Thomas Alexander Gerds; Bo Feldt-Rasmussen; Per Kragh Andersen; Rasmus W Licht

doi:10.1001/jamapsychiatry.2015.1834

Use of Lithium and Anticonvulsants and the Rate of Chronic Kidney Disease: A Nationwide Population-Based Study

Lars Vedel Kessing, Thomas Alexander Gerds, Bo Feldt-Rasmussen, Per Kragh Andersen, Rasmus W Licht

72 Citations (Scopus)

Abstract

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 aDanish nationwide population-based study of 2 cohorts. Cohort 1 comprised a randomly selected sample of 1.5 million individuals among all persons whowere 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 Atotal 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 2were diagnosed as having possible, definite, or end-stage CKD, respectively. Based on the total sample and not considering diagnoses, use of lithiumwas associated with an increased rate of definiteCKD (0 prescriptions: hazard ratio [HR] = 1.09, 95% CI, 0.81-1.45;≥60prescriptions: 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; ≥60prescriptions: HR = 2.88, 95%CI, 2.17- 3.81; P for trend < .001), whereas use of anticonvulsants, antipsychotics, or antidepressantswas not. Neither use of lithium nor use of any other drug classwas associated with increasing rates of end-stageCKD. In patients with bipolar disorder, use of lithiumwas associated with an increased rate of definiteCKD (1-2 prescriptions: HR = 0.89, 95%CI, 0.39-2.06; ≥60prescriptions: HR = 2.54, 95%CI, 1.81-3.57; P for trend 7lt;.001) or possibleCKD (1-2 prescriptions: HR = 1.26, 95%CI, 0.65-2.43; ≥60prescriptions, HR = 2.48, 95%CI, 1.80-3.42; P for trend < .001), aswas use of anticonvulsants (definiteCKD, 1-2 prescriptions: HR = 1.23, 95%CI, 0.76-1.99; ≥60prescriptions, HR = 2.30, 95%CI, 1.53-3.44; P for trend < .001; possibleCKD, 1-2 prescriptions: HR = 1.11, 95%CI, 0.70-1.76; ≥60prescriptions: HR = 1.97, 95%CI, 1.34-2.90; P for trend <.001). Therewas 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; ≥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.

Original language	English
Journal	J A M A Psychiatry
Volume	72
Issue number	12
Pages (from-to)	1182-91
Number of pages	10
ISSN	2168-622X
DOIs	https://doi.org/10.1001/jamapsychiatry.2015.1834
Publication status	Published - Dec 2015

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10.1001/jamapsychiatry.2015.1834

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@article{6069f718d82e4d3fa9e36566cef1521c,

title = "Use of Lithium and Anticonvulsants and the Rate of Chronic Kidney Disease: A Nationwide Population-Based Study",

abstract = "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 aDanish nationwide population-based study of 2 cohorts. Cohort 1 comprised a randomly selected sample of 1.5 million individuals among all persons whowere 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 Atotal 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 2were diagnosed as having possible, definite, or end-stage CKD, respectively. Based on the total sample and not considering diagnoses, use of lithiumwas associated with an increased rate of definiteCKD (0 prescriptions: hazard ratio [HR] = 1.09, 95% CI, 0.81-1.45;≥60prescriptions: 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; ≥60prescriptions: HR = 2.88, 95%CI, 2.17- 3.81; P for trend < .001), whereas use of anticonvulsants, antipsychotics, or antidepressantswas not. Neither use of lithium nor use of any other drug classwas associated with increasing rates of end-stageCKD. In patients with bipolar disorder, use of lithiumwas associated with an increased rate of definiteCKD (1-2 prescriptions: HR = 0.89, 95%CI, 0.39-2.06; ≥60prescriptions: HR = 2.54, 95%CI, 1.81-3.57; P for trend 7lt;.001) or possibleCKD (1-2 prescriptions: HR = 1.26, 95%CI, 0.65-2.43; ≥60prescriptions, HR = 2.48, 95%CI, 1.80-3.42; P for trend < .001), aswas use of anticonvulsants (definiteCKD, 1-2 prescriptions: HR = 1.23, 95%CI, 0.76-1.99; ≥60prescriptions, HR = 2.30, 95%CI, 1.53-3.44; P for trend < .001; possibleCKD, 1-2 prescriptions: HR = 1.11, 95%CI, 0.70-1.76; ≥60prescriptions: HR = 1.97, 95%CI, 1.34-2.90; P for trend <.001). Therewas 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; ≥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.",

author = "Kessing, {Lars Vedel} and Gerds, {Thomas Alexander} and Bo Feldt-Rasmussen and Andersen, {Per Kragh} and Licht, {Rasmus W}",

note = "Error in Author Affiliations JAMA Psychiatry. 2016;73(2):179. doi:10.1001/jamapsychiatry.2015.3326 ",

year = "2015",

month = dec,

doi = "10.1001/jamapsychiatry.2015.1834",

language = "English",

volume = "72",

pages = "1182--91",

journal = "J A M A Psychiatry",

issn = "2168-622X",

publisher = "The JAMA Network",

number = "12",

}

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 aDanish nationwide population-based study of 2 cohorts. Cohort 1 comprised a randomly selected sample of 1.5 million individuals among all persons whowere 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 Atotal 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 2were diagnosed as having possible, definite, or end-stage CKD, respectively. Based on the total sample and not considering diagnoses, use of lithiumwas associated with an increased rate of definiteCKD (0 prescriptions: hazard ratio [HR] = 1.09, 95% CI, 0.81-1.45;≥60prescriptions: 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; ≥60prescriptions: HR = 2.88, 95%CI, 2.17- 3.81; P for trend < .001), whereas use of anticonvulsants, antipsychotics, or antidepressantswas not. Neither use of lithium nor use of any other drug classwas associated with increasing rates of end-stageCKD. In patients with bipolar disorder, use of lithiumwas associated with an increased rate of definiteCKD (1-2 prescriptions: HR = 0.89, 95%CI, 0.39-2.06; ≥60prescriptions: HR = 2.54, 95%CI, 1.81-3.57; P for trend 7lt;.001) or possibleCKD (1-2 prescriptions: HR = 1.26, 95%CI, 0.65-2.43; ≥60prescriptions, HR = 2.48, 95%CI, 1.80-3.42; P for trend < .001), aswas use of anticonvulsants (definiteCKD, 1-2 prescriptions: HR = 1.23, 95%CI, 0.76-1.99; ≥60prescriptions, HR = 2.30, 95%CI, 1.53-3.44; P for trend < .001; possibleCKD, 1-2 prescriptions: HR = 1.11, 95%CI, 0.70-1.76; ≥60prescriptions: HR = 1.97, 95%CI, 1.34-2.90; P for trend <.001). Therewas 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; ≥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 aDanish nationwide population-based study of 2 cohorts. Cohort 1 comprised a randomly selected sample of 1.5 million individuals among all persons whowere 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 Atotal 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 2were diagnosed as having possible, definite, or end-stage CKD, respectively. Based on the total sample and not considering diagnoses, use of lithiumwas associated with an increased rate of definiteCKD (0 prescriptions: hazard ratio [HR] = 1.09, 95% CI, 0.81-1.45;≥60prescriptions: 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; ≥60prescriptions: HR = 2.88, 95%CI, 2.17- 3.81; P for trend < .001), whereas use of anticonvulsants, antipsychotics, or antidepressantswas not. Neither use of lithium nor use of any other drug classwas associated with increasing rates of end-stageCKD. In patients with bipolar disorder, use of lithiumwas associated with an increased rate of definiteCKD (1-2 prescriptions: HR = 0.89, 95%CI, 0.39-2.06; ≥60prescriptions: HR = 2.54, 95%CI, 1.81-3.57; P for trend 7lt;.001) or possibleCKD (1-2 prescriptions: HR = 1.26, 95%CI, 0.65-2.43; ≥60prescriptions, HR = 2.48, 95%CI, 1.80-3.42; P for trend < .001), aswas use of anticonvulsants (definiteCKD, 1-2 prescriptions: HR = 1.23, 95%CI, 0.76-1.99; ≥60prescriptions, HR = 2.30, 95%CI, 1.53-3.44; P for trend < .001; possibleCKD, 1-2 prescriptions: HR = 1.11, 95%CI, 0.70-1.76; ≥60prescriptions: HR = 1.97, 95%CI, 1.34-2.90; P for trend <.001). Therewas 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; ≥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

SN - 2168-622X

VL - 72

SP - 1182

EP - 1191

JO - J A M A Psychiatry

JF - J A M A Psychiatry

IS - 12

ER -

Use of Lithium and Anticonvulsants and the Rate of Chronic Kidney Disease: A Nationwide Population-Based Study

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