Opioids and NSAIDs are the most commonly used analgesics for managing pain in patients with chronic kidney disease (CKD), but these therapies come with important risks. “NSAIDs have direct nephrotoxic effects that may lead to fluid and electrolyte imbalances, hypertension, and other complications,” explains Rajiv Saran, MD. “Toxic side effects from opioid use can also accumulate in patients with reduced kidney function. In serious cases, such as those with repetitive hypotension, this can result in faster progression of kidney damage due to diminished blood flow in the kidneys (renal ischemia) and repetitive acute kidney injury.”

Patients with CKD are at risk for receiving suboptimal pain control and inappropriate use of prescription analgesics. “The opioid epidemic has received considerable attention from clinicians, policymakers, and the public,” says Yun Han, PhD. “However, few studies have assessed analgesic use and outcomes in patients with reduced kidney function, particularly the long-term effects.”

Robust New Data

Dr. Saran, Dr. Han, and colleagues had a study published in JAMA Open Network that examined trends in opioid and prescription NSAID use among adults aged 65 and older with CKD in the United States from 2006 to 2015. “We explored factors associated with opioid and NSAID use and outcomes associated with their use, focusing on end-stage kidney disease (ESKD) and death,” says Dr. Han. “Understanding these patterns and associations with outcomes may raise awareness of this issue and help inform quality improvement and policy to optimize pain management in these complex patients.”

For the study, researchers used the 5% Medicare claims data (2005-2015) to select 10 retrospective annual cohorts of Medicare Part D beneficiaries aged 65 and older from 2006-2015 and a retrospective longitudinal cohort. More than 6.2 million beneficiaries—9.6% of which were identified with CKD according to claims—were selected in the annual cohorts, and nearly 650,000 beneficiaries—8.3% of which were identified with CKD—were selected in the longitudinal cohort.

Important Findings

“Our study found that opioids and prescription NSAIDs have been increasingly used by older patients with CKD in the U.S. except until very recently,” says Dr. Saran. “Recent signs of decreased use may be owing to heightened awareness of the opioid epidemic.” Among patients with CKD, opioid use ranged from about 31% to 42% throughout the study period whereas NSAID use ranged from 11% to 17%. Long-term use of opioids increased from 2006 to 2014, rising from about 26% to 37%, but decreased through 2015 to approximately 36%. Long-term use of NSAIDs remained stable from 2006 to 2015.

The study also observed substantial geographic variations in opioids and NSAIDS use, suggesting that pain management practices vary across the country, says Dr. Han. In addition, opioid use was associated with progression to ESKD and death, regardless of CKD status and other covariates. Conversely, there appeared to be an inverse association between NSAID use and death (Table).

“These data highlight the need for careful monitoring of prescription practices with respect to pain management,” Dr. Saran says. “This is particularly important when managing patients who have CKD with potentially toxic and/or habit-forming drugs. Our study also suggests potential benefits with using NSAIDs instead of opioids for pain management. We must continue to monitor these trends and develop optimal protocols for pain management in older individuals with CKD.”

Evaluating Implications

According to Dr. Saran and Dr. Han, greater awareness by nephrologists and primary care providers on the importance of rational pain management in CKD is a critical first goal. “Clinical practice guidelines for pain management in patients with kidney disease may go a long way toward improving care for these patients, who often have multiple comorbidities,” says Dr. Saran. “Nonpharmacologic pain management strategies, such as physical therapy, ice-packs, acupuncture, and other alternatives, should be actively considered and individualized to reduce exclusive dependence on pharmacotherapy.”

Future research should further investigate the relationship of geographic variations in pain management practices in the context of environmental and social determinants of health, according to Dr. Han. “Such studies would help identify areas with greater need for resource allocation and guide appropriate policy changes to foster optimal pain management strategies,” she says. “Finding alternative nonpharmacologic pain management approaches and addressing the root causes of pain are important and deserve greater attention from the research and medical practice community.”