Increased Risk of End-Stage Renal Disease (ESRD) Requiring Chronic Dialysis is Associated With Use of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Nationwide Case-Crossover Study

Abstract

It is known that many medical adverse events can be caused by nonsteroidal anti-inflammatory drugs (NSAIDs); however, epidemiologic evidence has not granted an affirmative relationship between NSAID use and the risk of end-stage renal disease (ESRD). We aimed to investigate the relationship in a Chinese population between short-term NSAID use and development of ESRD requiring chronic dialysis. A retrospective case-crossover design was used in this study. Using the Taiwanese National Health Insurance database, we identified 109,400 incident chronic ESRD patients with dialysis initiation from 1998 to 2009. For each patient, we defined the case period as 1 to 14 days and the control period as 105 to 118 days, respectively, before the first dialysis date. The washout period was 90 days between the case and control period. Detailed information about NSAID use was compared between the case and control periods. We calculated odds ratios (ORs) and their 95% confidence intervals (CIs) using a conditional logistic regression model. NSAID use was found to be a significant risk factor associated with dialysis commencement. The adjusted OR was 2.73 (95% CI: 2.62-2.84) for nonselective NSAIDs and 2.17 (95% CI: 1.83-2.57) for celecoxib. The OR reached 3.05 for the use of acetic acid derivatives. Compared with the oral forms, significantly higher risks were seen in parenteral NSAID use (OR: 8.66, 95% CI: 6.12-20.19). NSAIDs should be prescribed with caution, especially for those in ESRD high-risk groups.

FIGURE 1

Risks of end-stage renal disease requiring chronic dialysis associated with short-term exposure of nonsteroidal anti-inflammatory drugs, stratified by different exposure dosage A, and B, duration. (Q1: ≤0.25, Q2: 0.26–0.50, Q3:0.51–0.75, Q4: >0.75 define daily dose, ^∗P < 0.05). NSAIDs = nonsteroidal anti-inflammatory drugs, OR = odds ratio.

FIGURE 2

Risk of chronic dialysis associated with current use of nonsteroidal anti-inflammatory drugs, stratified by sex, age, comorbidity status, year of dialysis commencement, and acute medical events that occurred during the case period. CVD = cardiovascular disease, DM = diabetes mellitus, HTN = hypertension, ICU = intensive care unit, NSAIDs = nonsteroidal anti-inflammatory drugs, OR = odds ratio.