Analgesic use and the risk for progression of chronic kidney disease

Purpose: The chronic effect of various analgesics on the progression of chronic kidney disease (CKD) is inconclusive. There is also lack of information on the renal safety of selective cyclooxygenase-2 (COX-2) inhibitors. This study aimed to clarify the renal risk of analgesic use in CKD patients. Methods: A cohort study using a nationally representative database randomly sampled from National Health Insurance (NHI) enrollees was performed. The study population included a total of 19,163 newly diagnosed CKD patients. Clinical conditions were defined by diagnostic codes and exposure information on analgesics was derived from service claims. Cox proportional hazard model was used to assess the association between analgesic use and the risk of progression to end stage renal disease (ESRD). Results: CKD patients using acetaminophen, aspirin, and non-selective non-steroidal anti-inflammatory drugs (NSAIDs) had an increased risk for ESRD with multivariable-adjusted HRs (95%CIs) of 2.92 (2.47-3.45), 1.96 (1.62-2.36), and 1.56 (1.32-1.85), respectively. The trends toward higher risk with increasing exposure dose were significant for all classes of analgesics (all P for trend < 0.001). Among COX-2 inhibitors, only rofecoxib, but not celecoxib, shows a significant risk association with ESRD (HR = 1.98; 95%CI, 1.15-3.40). Conclusions: Our data indicated exacerbating effects of acetaminophen, aspirin, and non-selective NSAIDs on CKD in a dose-dependent manner. For COX-2 inhibitors, only rofecoxib showed an increased risk for ESRD. Although the possibility of residual confounding cannot be completely ruled out, given the common use of analgesics, the possible relation suggested by this study warrants further investigation.