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

Abstract

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.

Keywords: COX-2 inhibitor; Chronic kidney disease (CKD); analgesics; drug safety; end-stage renal disease (ESRD); kidney disease progression; kidney function; non-steroidal anti-inflammatory drug (NSAID); opioids; outcomes; pain management.