#2559: Second-generation antipsychotics and the risk of chronic kidney disease: A population-based case-control study

Background: Second-generation antipsychotics (SGA) are associated with development of metabolic disturbances which can lead to cardiovascular and renal disease. Methods: We conducted a population-based case-control study by identifying 21,434 cases of incident CKD from 2001 to 2016 in the Funen Laboratory Cohort containing more than 7.7 million creatinine samples. Cases were identified based on creatinine measurements and matched by risk-set sampling to four population controls using age, sex, and calendar year. We obtained information on drug exposure and comorbidities from the Danish National Prescription Register and the Danish National Patient Register. We calculated odds ratios (OR) for the association between SGA use and CKD using conditional logistic regression. Results: Use of SGAs was associated with increased risk of CKD among ever-users (OR 1.24, 95%CI: 1.12-1.37) and current users (OR 1.26, 95%CI: 1.12-1.42). We found no clear evidence of dose-response-relationship. Both short duration (1-2 antipsychotic prescriptions; OR 1.22, 95%CI: 1.01-1.48), as well as long-term use (>30 prescriptions; OR 1.45, 95%CI 1.19-1.76) were associated with an increased risk of CKD. Both use of SGAs with mild and high risk of metabolic disturbances was associated with increased risk of CKD (Mild risk: OR 1.21, 95%CI: 1.06-1.39 and high risk OR 1.36, 95%CI: 1.11-1.68). Recent use of NSAIDs, prior use of lithium, hypertension, or prior AKI were not clearly associated with development of CKD in connection to SGA exposure. All SGAs, except for aripiprazole, were associated with increased risk of CKD, and the highest risk was found for clozapine (OR 1.81, 95%CI: 1.22-2.69). Conclusions: Use of SGA is associated with a small-to-moderately increased risk of incident CKD. All investigated second-generation antipsychotics, except for aripiprazole, were associated with an increased risk of CKD.