Association of Opioids and Nonsteroidal Anti-inflammatory Drugs With Outcomes in CKD: Findings From the CRIC (Chronic Renal Insufficiency Cohort) Study.

RATIONALE & OBJECTIVE: Safe analgesic choices are limited in chronic kidney disease (CKD). We conducted a comparative analysis of harm from opioids versus nonsteroidal anti-inflammatory drugs (NSAIDs) in CKD. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 3,939 patients with CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study. EXPOSURES: 30-day analgesic use reported at annual visits. OUTCOMES: A composite outcome of 50% glomerular filtration rate reduction and kidney failure requiring kidney replacement therapy (KRT), as well as the outcomes of kidney failure requiring KRT, hospitalization, and pre-kidney failure death. ANALYTICAL APPROACH: Marginal structural models with time-updated exposures. RESULTS: Participants were followed up for a median of 6.84 years, with 391 (9.9%) and 612 (15.5%) reporting baseline opioid and NSAID use, respectively. Time-updated opioid use was associated with the kidney disease composite outcome, kidney failure with KRT, death (HRs of 1.4 [95% CI, 1.2-1.7], 1.4 [95% CI, 1.1-1.7], and 1.5 [95% CI, 1.2-2.0], respectively), and hospitalization (rate ratio [RR], 1.7; 95% CI, 1.6-1.9) versus opioid nonusers. Similar results were found in an analysis restricted to a subcohort of participants reporting ever using other (nonopioid and non-NSAID) analgesics or tramadol. Time-updated NSAID use was associated with increased risk for the kidney disease composite (HR, 1.2; 95% CI, 1.0-1.5) and hospitalization (RR, 1.1; 95% CI, 1.0-1.3); however, these associations were not significant in the subcohort. The association of NSAID use with the kidney disease composite outcome varied by race, with a significant risk in blacks (HR, 1.3; 95% CI, 1.0-1.7). NSAID use was associated with lower risk for kidney failure with KRT in women and individuals with glomerular filtration rate<45mL/min/1.73m2 (HRs of 0.63 [95% CI, 0.45-0.88] and 0.77 [95% CI, 0.59-0.99], respectively). LIMITATIONS: Limited periods of recall of analgesic use and potential confounding by indication. CONCLUSIONS: Opioid use had a stronger association with adverse events than NSAIDs, with the latter's association with kidney disease outcomes limited to specific subgroups, notably those of black race.

Duke Scholars

Author Clarissa Jonas Diamantidis Medicine, General Internal Medicine