CKD patients have worse outcomes with opioids versus NSAIDs

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Among patients with CKD, those taking opioids have a higher rate of adverse outcomes than those taking nonsteroidal anti-inflammatory drugs (NSAIDs), reports a study in the American Journal of Kidney Diseases.

Using data from the Chronic Renal Insufficiency Cohort (CRIC), the researchers analyzed the relationship between analgesic use and clinical outcomes in patients with CKD. The analysis included 3939 CRIC participants with CKD not requiring kidney replacement therapy (KRT). The patients reported 30-day analgesic use at annual study visits. At baseline, 9.9% of patients were using opioids and 15.5% were taking NSAIDs.

Adverse outcomes were compared for groups with differing patterns of analgesic use. The analysis focused on four clinical outcomes: kidney failure requiring KRT, a composite of kidney failure with KRT plus a 50% reduction in eGFR, death before development of kidney failure, and number of hospital admissions (without kidney failure) between annual study visits. The median follow-up time was 6.84 years.

Time-updated opioid use was associated with increased risk of all four outcomes of interest: HR 1.4 for the composite outcome, 1.4 for kidney failure requiring KRT, and 1.5 for death; and rate ratio 1.7 for hospitalization, compared with patients not taking opioids. Similar patterns were found on subgroup analysis of patients reporting any use of analgesics other than opioids or NSAIDs or tramadol.

By contrast, for time-updated NSAID use, the associations were smaller and were nonsignificant on subgroup analysis. Some associations varied with patient characteristics, including a significant increase in the composite outcome among black patients taking NSAIDs: HR 1.3. For women and for patients with eGFR <45 mL/min per 1.73 m2, NSAID use was associated with a lower risk of kidney failure: HR 0.63 and 0.77, respectively.

Pain is a common problem among CKD patients, who have limited safe options for analgesia. There are conflicting recommendations as to the safety of NSAIDs in patients with CKD. Some patients use opioids as a supplement to or replacement for NSAID treatment for pain.

This comparative analysis of CRIC data suggests that opioids are more strongly related to adverse kidney outcomes in patients with CKD, compared with NSAIDs. Associations of NSAIDs with adverse outcomes may be limited to certain subgroups, particularly black patients. The researchers write, “Both classes of agents have recognized risk profiles that are likely amplified in CKD, justifying close consideration of their risk versus benefit” [Zhan M, et al. Association of opioids and nonsteroidal anti-inflammatory drugs with outcomes in CKD: Findings from the CRIC (Chronic Renal Insufficiency Cohort) study. Am J Kidney Dis doi: 10.1053/j.ajkd.2019.12.010].