Chronic pain is highly prevalent among adults treated with maintenance haemodialysis (HD) and has profound negative effects. Over four decades, research has demonstrated that 50–80% of adult patients treated with HD report having pain. Half of patients with HD-dependent kidney failure (HDKF) have chronic moderate-to-severe pain, which is similar to the burden of pain in patients with cancer. However, pain management in patients with HDKF is often ineffective as most patients report that their pain is inadequately treated. Opioid analgesics are prescribed more frequently for patients receiving HD than for individuals in the general population with chronic pain, and are associated with increased morbidity, mortality and health-care resource use. Furthermore, current opioid prescribing patterns are frequently inconsistent with guideline-recommended care. Evidence for the effectiveness of opioids in pain management in general, and in patients with HDKF specifically, is lacking. Nonetheless, long-term opioid therapy has a role in the treatment of some patients when used selectively, carefully and combined with an ongoing assessment of risks and benefits. Here, we provide a comprehensive overview of the use of opioid therapy in patients with HDKF and chronic pain, including a discussion of buprenorphine, which has potential as an analgesic option for patients receiving HD owing to its unique pharmacological properties.
Patients with kidney failure treated with haemodialysis have a pain burden that is comparable to that of patients with cancer and correlates with poor health outcomes. However, pain management is often ineffective in this population.
Opioid therapy can be an important pain management tool for patients treated with maintenance haemodialysis but opioids are frequently overprescribed and are associated with increased dialysis discontinuation, hospitalization and mortality.
Opioid use is associated with many potential risks and their risk–benefit ratio is not always clear. The use of opioids must be personalized, based on shared decision-making and implemented cautiously.
Kidney failure and haemodialysis can affect the pharmacokinetics and metabolism of certain opioids profoundly, which complicates their use in clinical practice; special prescribing considerations are necessary.
Buprenorphine has several unique pharmacological properties that make it an appealing analgesic option for patients treated with maintenance haemodialysis but effective prescribing requires a nuanced understanding of its special characteristics.
Monitoring for harm and the emergence of opioid use disorder in patients who are prescribed opioids is crucial. Screening for and managing opioid use disorder is an important aspect of safe opioid prescribing.
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M.B.L., W.C.B. and M.J.F. were supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the NIH under Award Number U01DK123787. M.J. was supported by the NIDDK of the NIH under Award Number U01DK123812A. P.L.K. is a Senior Advisor at NIDDK. M.B.L. was supported by the National Institute of Nursing Research of the NIH under Award Number K23NR018482. L.M.D. was supported by the NIDDK of the NIH under Award Number U01DK123813. The content is solely the responsibility of the authors. The views expressed in this paper do not necessarily represent the views of the NIDDK, the NIH, the Department of Health and Human Services, the Department of Veterans Affairs, or the government of the United States. The authors acknowledge A. Abelleira from the VA Connecticut Healthcare System in West Haven, CT, for assistance in drafting and reviewing pharmacological content presented in the tables before submission.
D.G.T. works as an expert witness for cases involving opioids. P.L.K. is a Co-Editor of Chronic Renal Disease (Academic Press) and Psychosocial Aspects of Chronic Kidney Disease, and receives royalties from Elsevier. L.M.D. receives compensation from the National Kidney Foundation for her role as a Deputy Editor of the American Journal of Kidney Diseases, and consulting fees from Merck, Cara Therapeutics and Astra Zeneca. N.D.E. receives fees from work as a scientific advisor for Somatus. T.D.N. receives consulting fees from MediBeacon and CytoSorbents, and royalties from McGraw-Hill Education. The other authors declare no competing interests.
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American Medical association opioid CME course: https://edhub.ama-assn.org/pages/opioid-cme-course
Hemodialysis Opioid Prescribing Effort (HOPE) Consortium: https://www.niddk.nih.gov/research-funding/researchprograms/hemodialysis-opioid-prescription-effort-consortium
Opioid use disorder symptoms and severity: https://pcssnow.org/resource/opioid-use-disorder-opioid-addiction/
Risk Evaluation and Mitigation Strategies courses: https://search.opioidanalgesicrems.com/RPC-RMS-PROD/Guest/GuestPageExternal.aspx
- Nociceptive pain
A type of pain that occurs due to the activation of nociceptors in the peripheral nervous system by noxious stimuli, including tissue injury, inflammation or disease.
- Neuropathic pain
A form of pain caused by a lesion or disease of the somatosensory nervous system.
- Morphine milligram equivalents
(MMEs). A dose that is calculated to be equivalent to a morphine dose based on the equi-analgesic potency of the opioid relative to morphine.
- Abuse-deterrent opioid formulations
Opioid formulations designed to resist or discourage physical or chemical adulteration of the drug (for example, by crushing, smoking, extracting or injecting the drug) while remaining safe and effective when used as intended.
- Prescription drug monitoring programs
(PDMPs). An electronic database that tracks and records controlled substance prescribing and dispensing data for patients.
- Partial opioid agonist
A drug that binds to and activates opioid receptors, but causes less receptor conformational change and activation than a full opioid agonist.
- Opioid antagonist
A drug that competitively binds to an opioid receptor without activating it, thus preventing receptor conformational change, and/or displacing and reversing the effects of a drug that previously activated the receptor.
- Corrected QT interval
(QTc). The time from the Q wave to the T wave (Q-T interval) on an electrocardiogram, divided by the square root of the time between successive R waves (R-R interval).
- Torsades de pointes
A form of polymorphic ventricular tachycardia that is characterized by a gradual change in the amplitude and twisting of the QRS complexes around the isoelectric line in an electrocardiogram.
- Opioid-tolerant individual
A patient with previous opioid exposure who can safely receive an opioid dose that would be otherwise dangerous without earlier repeated opioid exposure.
- Volume of distribution
The volume necessary to contain the total amount of an administered drug at the same concentration measured in plasma.
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Tobin, D.G., Lockwood, M.B., Kimmel, P.L. et al. Opioids for chronic pain management in patients with dialysis-dependent kidney failure. Nat Rev Nephrol 18, 113–128 (2022). https://doi.org/10.1038/s41581-021-00484-6
Nature Reviews Nephrology (2022)