LONG-TERM OPIOID AND GABAPENTINOID RELATED HARMS AMONG ADULTS WITH CHRONIC KIDNEY DISEASE: A TIME-UPDATED, POPULATION-BASED COHORT STUDY

Over half of patients with chronic kidney disease (CKD) live with chronic pain. Optimal management strategies are unclear, however, despite a limited evidence base, half of patients with CKD are treated with opioids and a fifth receive gabapentinoids each year. Long-term safety data relating to new opioid or gabapentinoid use, which accounts for prevalent use among adults with non-dialysis dependent CKD, are lacking. This study aimed to establish the risks of new long-term opioid or gabapentinoid use for chronic pain among adults with CKD.

A retrospective, population-based cohort study was performed using linked national datasets (i.e. the Scottish morbidity record, cancer register, renal registry, SCI-Diabetes collaboration, prescribing information and deaths data). The study included adults from the East of Scotland with CKD from 1st Jan 2010-23. The primary exposure was new long-term (i.e. 90 per 180 days) use of opioids and/or gabapentinoids for pain. Cumulative analgesic exposure was defined using the refill-gap method with a permissible gap of 28 days. The primary outcome was all-cause mortality. Patients were followed from CKD diagnosis until the earliest of death, exit from health board or 1st Jan 2024. Prevalent analgesic users were excluded from the primary new user analysis. A discrete time logistic model was used to assess the impact of cumulative analgesic exposure on mortality risk. The model controlled for allocation bias by including joint terms for ever/never analgesic use and cumulative exposure, with adjustment for baseline socioeconomic status, and time-updated age, CKD duration, eGFR, cardiovascular disease, cancer, depression, diabetes and chronic respiratory disease with sex stratification. The study was pre-registered via the Open Science Framework (osf.io/5qsyh).

30,674 patients were diagnosed with CKD during the study period and following exclusions (n=163). Table 1 outlines the characteristics of the study cohort at baseline stratified by prevalent analgesic use. 9,220 (30.1%) were prevalent opioid or gabapentinoid users in the six months prior to CKD diagnosis. The most frequently prescribed opioid items were co-codamol, tramadol and codeine (4,055, 2,075 and 1,236 prescriptions, respectively) whilst gabapentin was prescribed more often than pregabalin (1,273 vs 742 prescriptions). 11,961 (38.9%) patients died during a median of 4.2 years of follow-up (range 0-13 years). Among 21,454 patients with CKD, but without prior opioid or gabapentinoid use, 2,399 (11.2%) and 350 (1.6%) received at least one 90-day continuous stretch of opioids and gabapentinoids, respectively. A discrete time logistic model showed that each additional 90-day cumulative exposure to opioids was associated with a 2.7% (OR 1.03 [95% CI 1.02-1.04]) and 2.2% (OR 1.02 [95% CI 1.01-1.03]) increased risk of mortality, in males and females, respectively. There was no association between long-term gabapentinoid use and death. Sensitivity analyses employing a shorter permissible gap or alternative CKD definition did not substantially alter the results. 

Long-term use of opioids is associated with an increased risk of mortality among adults with CKD and without prior analgesic exposure. Cumulative gabapentinoid use is not associated with death in such patients. This abstract was also submitted for the Scottish Renal Association meeting as permitted.