Use of Lithium and Anticonvulsants and the Rate of Chronic Kidney Disease.

Use of Lithium and Anticonvulsants and the Rate of Chronic Kidney Disease.
JAMA Psychiatry. November 04, 2015.

DESIGN:
* Danish nationwide population-based study of 2 cohorts.
* Cohort 1: 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: subgroup of 10 591 patients diagnosed as having bipolar disorder.

RESULTS:
(A)
* Cohort 1: total of 14 727 (0.8%), 18 762 (1.0%), and 3407 (0.2%) diagnosed as having possible, definite, or end-stage CKD, respectively.
* Cohort 2: total of 278 (2.6%), 319 (3.0%), and 62 (0.6%) diagnosed as having possible, definite, or end-stage CKD, respectively.

(B)
* Based on the total sample and not considering diagnoses, use of lithium was associated with:
# increased rate of definite CKD (0 prescriptions: hazard ratio = 1.09, 95% CI, 0.81-1.45; ≥60 prescriptions: HR = 3.65, 95% CI, 2.64-5.05; P for trend < .001) and
# increased rate of 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)

* Based on the total sample and not considering diagnoses, use of anticonvulsants, antipsychotics, or antidepressants was not associated with increased rate of definite or possible CKD.

* Based on the total sample and not considering diagnoses, Neither use of lithium nor use of any other drug class was associated with increasing rates of end-stage CKD.

(C)
* In patients with bipolar disorder, use of lithium was associated with:
# 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
# increased rate of 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),
* In patients with bipolar disorder, use of anticonvulsants was associated with:
# increased rate of 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)
# increased rate of 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.

(D) Also in patients with bipolar disorder
* use of lithium was not significantly associated with an increased rate of end-stage CKD
* use of anticonvulsants was associated with an increased rate of end-stage CKD (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.