Background: Studies have examined the association between acetaminophen (APAP) use and renal disease; however, their interpretation is limited by a number of methodological issues.
Objective: To study the association between acute and chronic prescription-acquired APAP use and renal disease.
Methods: This was a retrospective case-control study of medical and pharmacy claims of a 10% random sample of the enrollees from the IMS LifeLink Health Plans commercial claims dataset for dates of service from January 1, 1997, through December 31, 2009. Subjects were continuously enrolled and aged 18 years or older. Cases had at least 1 incident claim of renal disease defined by ICD-9-CM codes in the primary diagnosis field. Controls were randomly selected from individuals without evidence of renal disease, liver disease, or asthma in medical claims and matched to cases in a 3-to-1 ratio based on 3 variables (age, gender, and geographic region). APAP exposure, dosage, and duration of use were measured in the 7 and 30 days (acute) and in the 1-year (chronic) look-back periods. Multivariable conditional logistic regression was used to estimate the risk of APAP exposure adjusted for comorbidities, use of other nephrotoxic drugs, and health system factors.
Results: There were 4,724 cases and 14,172 controls with a mean (SD) age of 60.8 (17.8) years, and 52.6% were males; 10.9% of cases and 4.2% of controls had APAP exposure in the 30 days pre-index with mean potential maximum daily dosages of 3,846.5 mg and 3,190.8 mg, respectively. Acute APAP exposure was significantly associated with renal disease, and the risk decreased with longer look-back periods (7 days: adjusted odds ratio [OR] = 1.93, 95% CI = 1.61-2.30); 30 days: OR = 1.71, 95% CI = 1.48-1.97). Cumulative APAP dosage greater than 1 kg and APAP use for longer than 30 days in the pre-index year were not significantly associated with an increased risk of renal disease (both P values = 0.900).
Conclusions: Acute prescription-acquired APAP use was associated with renal disease, while chronic use was not. Because this study assessed APAP use in pharmacy claims, further research accounting for over-the-counter APAP use is warranted before the safety of chronic APAP consumption can be firmly established.