Fig. 1

Study design and definition of exposure. A In analysis 1, we aimed to investigate the association between proton pump inhibitor (PPI) use and the development of acute kidney injury (AKI). The start of the observation was defined as the earliest date of the first serum creatinine measurement or PPI prescription. The end of observation was defined as the latest data of the last serum creatinine measurement, 30 days after the end of last administration of a PPI, or date of death. PPI exposure period (risk period) was defined as the period from the start of PPI administration to 30 days after the end of administration. B In analysis 2, we evaluated the effect of concomitant use of macrolide antibiotics on the risk of AKI only during the initial PPI exposure period. The exposure period of macrolide antibiotics (risk period) was defined as the period from the start of macrolide antibiotics administration to 14 days after the end of its administration