Compared with nonusers, high-dose users had a 26% increased risk of rapid CKD progression.
High cumulative exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk for rapid CKD progression in the elderly, new data suggest.
The frequency of NSAID use has risen during the past few years because of increased OTC availability, an aging population, and the perceived superior safety profile of cyclooxygenase-2 (COX-2) inhibitors. Elderly persons have high rates of both NSAID use and CKD, and may be particularly susceptible to the nephrotoxic effects of these drugs.
A team led by Bruce Culleton, MD, of the University of Calgary in Alberta, studied 10,184 community-based individuals aged 66 years and older who were not receiving hemodialysis and were without acutely unstable renal function.
The researchers evaluated renal function using the glomerular filtration rate (GFR). The primary study end point was rapid progression of renal disease, defined as a GFR decrease of 15 mL/min/1.73m2 or greater during a median follow-up period of 2.75 years.
Dr. Culleton and his colleagues categorized patients into nonusers (no use of any NSAID during the study period), low-dose users (cumulative dose below the 90th percentile) and high-dose users (cumulative dose in 90th percentile or higher). NSAID use was inversely associated with age and comorbidity score and directly associated with a higher mean baseline GFR.
The primary study end point was documented in 1,353 patients (13.3%), as reported in the American Journal of Medicine (2007;120:280.e1-280.e7). Compared with NSAID nonusers, high-dose users had a 26% increased risk of achieving the primary study outcome after adjusting for age, sex, mean GFR, diabetes, and comorbidity.
Among patients with a mean GFR of 60-89 mL/min/1.73 m2, COX-2 inhibitor users had a 25% increased risk of rapid progression of CKD and traditional NSAID users had a 29% increased risk as compared with NSAID nonusers.
The association between NSAID use and rapid progression of CKD was significant only in patients with a mean baseline GFR of 60-89 mL/min/1.73 m2. Each 100-unit increase in daily NSAID dose was associated with decrease in GFR of 0.08 mL/min/1.73m2 during the follow-up period. No risk differential was observed between selective and nonselective NSAIDs.
Nonselective NSAIDs and COX-2 inhibitors should be used with caution in older persons with CKD, and chronic exposure to any NSAID should be avoided.