The exposure to NSAIDs was always assessed prior to the index date. Use of more
than one NSAID was evaluated separately and mutually exclusive categories of individual
NSAID exposure compared to non-exposure were considered. The exposure to NSAIDs was
evaluated within three different observation periods (time windows): 90, 180, and 365 days
prior to the Index Date. The number of cases and controls using one or more than one NSAID
over the different time windows was reported in S1 Table. Patients receiving at least one
NSAID prescription in the first time window (within 90 days prior to the index date) were
Fig 1. Selection of cases and controls.
doi:10.1371/journal.pone.0122899.g001
Non-Steroidal Anti-Inflammatory Drugs Use and CKD Risk
PLOS ONE | DOI:10.1371/journal.pone.0122899 April 16, 2015 4 / 14
defined as “current users” and were investigated in more detail as more strictly related in time
to the onset of CKD.
To explore the effect of NSAID treatment duration of use on CKD risk, “cumulative exposure
to NSAIDs” was categorized in three classes among current users: less than or equal to 90
days, between 91 and 180 days, more than 180 days. For each prescription, the duration of exposure
was estimated by dividing the total amount of active principle in each prescription with
NSAID-specific defined daily dose (DDD). The estimated number of days of NSAID exposure
for each prescription issued during the observation period was summed up.