Analgesic use and the risk for progression of chronic kidney disease.
OBJECTIVE
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.
Kuo
Hsin-Wei
HW
Graduate Institute of Occupational Safety and Health, College of Health Science, Kaohsiung Medical University, Kaohsiung, Taiwan.
Tsai
Shang-Shyue
SS
Tiao
Mao-Meng
MM
Liu
Yi-Chun
YC
Lee
I-Ming
IM
Yang
Chun-Yuh
CY
D000082:Acetaminophen / Q000008:administration & dosage / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D000368:Aged; D000700:Analgesics / Q000008:administration & dosage / Q000009:adverse effects*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D016208:Databases, Factual; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007223:Infant; D007676:Kidney Failure, Chronic / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012306:Risk; D013624:Taiwan / Q000453:epidemiology; D055815:Young Adult
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D000082:Acetaminophen; D001241:Aspirin