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Prescription opioid use linked to higher mortality risk for patients with reduced kidney function
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While prescription opioid use was associated with increased mortality and hospitalization risks for all patients regardless of kidney function, researchers found the risk for death was highest among those with moderate to severe chronic kidney disease.
“An estimated 58% of individuals with CKD experience chronic pain, a prevalence two- [to] three-times that of the general population,” Tessa Novick, MD, MSW, of the department of internal medicine, division of nephrology, at Johns Hopkins University, and colleagues wrote. “Neuropathy, peripheral vascular disease and pain syndromes unique to kidney disease, such as osteodystrophy and calciphylaxis are common. However, kidney disease limits therapeutic options for pain control, in large part due to the relative contraindication to NSAIDs. Opioids are an alternative, and over 40% of individuals with advanced CKD have received opioid prescriptions ... Literature on risks associated with opioid use in kidney disease has largely focused on the dialysis population, and little is known about pre-dialysis CKD.”
Hypothesizing that higher doses of opioids would increase risk for adverse outcomes, researchers examined data from the Geisinger Health System of Pennsylvania related to 42,246 primary care patients with or without CKD who were receiving either opioids or NSAIDs between 2008 and 2017. Propensity matching was used to ensure similarity of the cohorts (mean age, 54 years; 56% were women; 3% were black) and patients with ESKD were excluded. The most commonly prescribed opioids included oxycodone, tramadol, hydrocodone and codeine.
Risk of death and hospitalization were compared between the opioid and NSAID groups, with researchers categorizing opioid medication exposure at time-varying oral morphine milligram equivalents ([MMEs] one to 59 or 60) across time-varied eGFR.
While prescription opioid use was associated with increased mortality and hospitalization risks for all patients regardless of kidney function, researchers found the risk for death was highest among those with moderate to severe chronic kidney disease.
When evaluated at eGFR 80 mL/min/1.73 m2, researchers found that, compared with NSAIDs, opioid prescriptions of one to 59 and at least 60 MMEs were associated with a higher risks for both death (HR = 1.70 and HR = 2.25, respectively) and hospitalization (HR = 1.38 and HR = 1.68). While the risk for hospitalization with opioid use did not appear to vary by level of eGFR, relative risk of death increased for patients at lower eGFR with higher opioid dose (eGFR of 40 mL/min/1.73 m2 and opioid prescription of 60 MME: HR for hospitalization = 1.46 vs. HR for death = 3.94).
Researchers concluded that, while studies of patients on dialysis have shown opioid use to be associated with increased risk for altered mental status, fractures, poor sleep and dialysis discontinuation in addition to death and hospitalization, this study is one of the first to evaluate patients with lower eGFRs who have not yet reached ESKD.
“The manifest clinical question is how to better treat pain in a population with limited therapeutic options,” they wrote. “More research is needed on optimal dosing in patients with reduced kidney function, and on dosing and risks associated with non-opioid therapies. For patients with reduced eGFR and opioid prescriptions, counseling about the possible risks associated with opioids, promotion of nonpharmacologic therapies and regular consideration of whether the benefit of pain control outweighs such risks is crucial.” – by Melissa J. Webb
Disclosures: Novick reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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