Long-Term Opioid and Gabapentinoid Related Harms in CKD

Chronic pain affects over half of the patients with chronic kidney disease (CKD). This study aimed to evaluate the association between new long-term opioids or gabapentinoids and the risk of death, hospitalization, and hip fractures in adults with CKD.

This is a retrospective, time-updated, population-based cohort study from the East of Scotland (N = 953,542) using linked routinely collected data. The study population included adults with biochemically confirmed CKD (estimated glomerular filtration rate [eGFR] <60 ml/min per 1.73 m²) without kidney failure from 2010 to 2023. The primary exposures were new, long-term cumulative opioids or gabapentinoids. Discrete time logistic regression modelling with generalized estimating equations and adjustment for relevant covariates and treatment allocation bias was used to determine the association between chronic analgesic use and all-cause mortality.

A total of 30,674 adults with CKD entered the study. Of them, 21,440 patients without prevalent analgesic use were included in the primary and secondary analyses (median follow-up 4.3 years). Among 2399 patients with at least 1 continuous 90-day episode of opioid prescriptions during follow-up, 1159 died. The risk of death increased as continuous 90-day opioid stretches (reference 0) increased from 1 (absolute risk of death: 0.4% [0.3-0.4]; odds ratio [OR]: 1.09 [1.06-1.12], P < 0.001) to 6 (absolute risk of death: 0.6% [0.5-0.7]; OR: 1.68 [1.41-2.00], P < 0.001). Long-term gabapentinoids were potentially associated with a modest increase in death amongst males (OR: 1.04 [1.00-1.08], P = 0.050), but not females (OR: 1.02 [0.99-1.05], P = 0.201).

Long-term opioid use is associated with increased mortality and hospitalization in adults with CKD independent of demographics, comorbidities, and treatment allocation bias. These findings support prioritization of safer pain management strategies in people with CKD.