Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Opioids for chronic pain management in patients with dialysis-dependent kidney failure

Abstract

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.

Key points

  • 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.

Your institute does not have access to this article

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Fig. 1: Factors contributing to altered pharmacokinetics in patients with HDKF.

References

  1. Davison, S. N. The prevalence and management of chronic pain in end-stage renal disease. J. Palliat. Med. 10, 1277–1287 (2007).

    PubMed  Google Scholar 

  2. Kimmel, P. L., Emont, S. L., Newmann, J. M., Danko, H. & Moss, A. H. ESRD patient quality of life: symptoms, spiritual beliefs, psychosocial factors, and ethnicity. Am. J. Kidney Dis. 42, 713–721 (2003).

    PubMed  Google Scholar 

  3. Murtagh, F. E., Addington-Hall, J. & Higginson, I. J. The prevalence of symptoms in end-stage renal disease: a systematic review. Adv. Chronic Kidney Dis. 14, 82–99 (2007).

    PubMed  Google Scholar 

  4. Shayamsunder, A. K., Patel, S. S., Jain, V., Peterson, R. A. & Kimmel, P. L. Sleepiness, sleeplessness, and pain in end-stage renal disease: distressing symptoms for patients. Semin. Dial. 18, 109–118 (2005).

    PubMed  Google Scholar 

  5. Weisbord, S. D. et al. Symptom burden, quality of life, advance care planning and the potential value of palliative care in severely ill haemodialysis patients. Nephrol. Dial. Transpl. 18, 1345–1352 (2003).

    Google Scholar 

  6. Weisbord, S. D. et al. Prevalence, severity, and importance of physical and emotional symptoms in chronic hemodialysis patients. J. Am. Soc. Nephrol. 16, 2487–2494 (2005).

    PubMed  Google Scholar 

  7. Abdel-Kader, K., Unruh, M. L. & Weisbord, S. D. Symptom burden, depression, and quality of life in chronic and end-stage kidney disease. Clin. J. Am. Soc. Nephrol. 4, 1057–1064 (2009).

    PubMed  PubMed Central  Google Scholar 

  8. Brkovic, T., Burilovic, E. & Puljak, L. Prevalence and severity of pain in adult end-stage renal disease patients on chronic intermittent hemodialysis: a systematic review. Patient Preference Adherence 10, 1131–1150 (2016).

    PubMed  PubMed Central  Google Scholar 

  9. Davison, S. N. & Jhangri, G. S. Impact of pain and symptom burden on the health-related quality of life of hemodialysis patients. J. Pain. Symptom Manage. 39, 477–485 (2010).

    PubMed  Google Scholar 

  10. Davison, S. N. Pain in hemodialysis patients: prevalence, cause, severity, and management. Am. J. Kidney Dis. 42, 1239–1247 (2003).

    PubMed  Google Scholar 

  11. Claxton, R. N., Blackhall, L., Weisbord, S. D. & Holley, J. L. Undertreatment of symptoms in patients on maintenance hemodialysis. J. Pain. Symptom Manage. 39, 211–218 (2010).

    PubMed  Google Scholar 

  12. Weisbord, S. D. et al. Renal provider recognition of symptoms in patients on maintenance hemodialysis. Clin. J. Am. Soc. Nephrol. 2, 960–967 (2007).

    PubMed  Google Scholar 

  13. Jankovic, S. M. et al. Nonsteroidal antiinflammatory drugs and risk of gastrointestinal bleeding among patients on hemodialysis. J. Nephrol. 22, 502–507 (2009).

    CAS  PubMed  Google Scholar 

  14. Whelton, A. Nephrotoxicity of nonsteroidal anti-inflammatory drugs: physiologic foundations and clinical implications. Am. J. Med. 106, 13S–24S (1999).

    CAS  PubMed  Google Scholar 

  15. Heel, R. C., Brogden, R. N., Speight, T. M. & Avery, G. S. Buprenorphine: a review of its pharmacological properties and therapeutic efficacy. Drugs 17, 81–110 (1979).

    CAS  PubMed  Google Scholar 

  16. Gudin, J. & Fudin, J. A narrative pharmacological review of buprenorphine: a unique opioid for the treatment of chronic pain. Pain. Ther. 9, 41–54 (2020).

    PubMed  PubMed Central  Google Scholar 

  17. Harris, T. J. et al. Pain, sleep disturbance and survival in hemodialysis patients. Nephrol. Dial. Transpl. 27, 758–765 (2012).

    Google Scholar 

  18. Weisbord, S. D. Patient-centered dialysis care: depression, pain, and quality of life. Semin. Dial. 29, 158–164 (2016).

    PubMed  Google Scholar 

  19. Smith, D., Wilkie, R., Croft, P., Parmar, S. & McBeth, J. Pain and mortality: mechanisms for a relationship. Pain 159, 1112–1118 (2018).

    PubMed  Google Scholar 

  20. Smith, D., Wilkie, R., Croft, P. & McBeth, J. Pain and mortality in older adults: the influence of pain phenotype. Arthritis Care Res. 70, 236–243 (2018).

    Google Scholar 

  21. Weisbord, S. D. et al. Associations of depressive symptoms and pain with dialysis adherence, health resource utilization, and mortality in patients receiving chronic hemodialysis. Clin. J. Am. Soc. Nephrol. 9, 1594–1602 (2014).

    PubMed  PubMed Central  Google Scholar 

  22. Davison, S. N. & Jhangri, G. S. The impact of chronic pain on depression, sleep, and the desire to withdraw from dialysis in hemodialysis patients. J. Pain. Symptom Manage. 30, 465–473 (2005).

    PubMed  Google Scholar 

  23. Cohen, S. D., Patel, S. S., Khetpal, P., Peterson, R. A. & Kimmel, P. L. Pain, sleep disturbance, and quality of life in patients with chronic kidney disease. Clin. J. Am. Soc. Nephrol. 2, 919–925 (2007).

    PubMed  Google Scholar 

  24. Cheatle, M. D. Biopsychosocial approach to assessing and managing patients with chronic pain. Med. Clin. North. Am. 100, 43–53 (2016).

    PubMed  Google Scholar 

  25. Wyne, A., Rai, R., Cuerden, M., Clark, W. F. & Suri, R. S. Opioid and benzodiazepine use in end-stage renal disease: a systematic review. Clin. J. Am. Soc. Nephrol. 6, 326–333 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Fillingim, R. B. et al. Sex-related psychological predictors of baseline pain perception and analgesic responses to pentazocine. Biol. Psychol. 69, 97–112 (2005).

    PubMed  Google Scholar 

  27. Campbell, C. M., Edwards, R. R. & Fillingim, R. B. Ethnic differences in responses to multiple experimental pain stimuli. Pain 113, 20–26 (2005).

    PubMed  Google Scholar 

  28. Fillingim, R. B. et al. Morphine responses and experimental pain: sex differences in side effects and cardiovascular responses but not analgesia. J. Pain. 6, 116–124 (2005).

    CAS  PubMed  Google Scholar 

  29. Hastie, B. A., Riley, J. L. & Fillingim, R. B. Ethnic differences and responses to pain in healthy young adults. Pain. Med. 6, 61–71 (2005).

    PubMed  Google Scholar 

  30. Schafer, G., Prkachin, K. M., Kaseweter, K. A. & Williams, A. C. Health care providers’ judgments in chronic pain: the influence of gender and trustworthiness. Pain 157, 1618–1625 (2016).

    PubMed  Google Scholar 

  31. Hoffman, K. M., Trawalter, S., Axt, J. R. & Oliver, M. N. Racial bias in pain assessment and treatment recommendations, and false beliefs about biological differences between blacks and whites. Proc. Natl Acad. Sci. USA 113, 4296–4301 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Chen, E. H. et al. Gender disparity in analgesic treatment of emergency department patients with acute abdominal pain. Acad. Emerg. Med. 15, 414–418 (2008).

    PubMed  Google Scholar 

  33. Berger, A. J. et al. Racial disparities in analgesic use amongst patients presenting to the emergency department for kidney stones in the United States. Am. J. Emerg. Med. 39, 71–74 (2021).

    PubMed  Google Scholar 

  34. FitzGerald, C. & Hurst, S. Implicit bias in healthcare professionals: a systematic review. BMC Med. Ethics 18, 19 (2017).

    PubMed  PubMed Central  Google Scholar 

  35. Drwecki, B. B. Education to identify and combat racial bias in pain treatment. AMA J. Ethics 17, 221–228 (2015).

    PubMed  Google Scholar 

  36. Drwecki, B. B., Moore, C. F., Ward, S. E. & Prkachin, K. M. Reducing racial disparities in pain treatment: the role of empathy and perspective-taking. Pain 152, 1001–1006 (2011).

    PubMed  Google Scholar 

  37. Greenwald, A. G., McGhee, D. E. & Schwartz, J. L. Measuring individual differences in implicit cognition: the implicit association test. J. Pers. Soc. Psychol. 74, 1464–1480 (1998).

    CAS  PubMed  Google Scholar 

  38. Bailie, G. R., Mason, N. A., Bragg-Gresham, J. L., Gillespie, B. W. & Young, E. W. Analgesic prescription patterns among hemodialysis patients in the DOPPS: potential for underprescription. Kidney Int. 65, 2419–2425 (2004).

    PubMed  Google Scholar 

  39. Feldman, R. et al. Improving symptom management in hemodialysis patients: identifying barriers and future directions. J. Palliat. Med. 16, 1528–1533 (2013).

    PubMed  PubMed Central  Google Scholar 

  40. Green, J. A. et al. Renal provider perceptions and practice patterns regarding the management of pain, sexual dysfunction, and depression in hemodialysis patients. J. Palliat. Med. 15, 163–167 (2012).

    PubMed  Google Scholar 

  41. Koncicki, H. M., Brennan, F., Vinen, K. & Davison, S. N. An approach to pain management in end stage renal disease: considerations for general management and intradialytic symptoms. Semin. Dial. 28, 384–391 (2015).

    PubMed  Google Scholar 

  42. Nagar, V. R., Birthi, P., Salles, S. & Sloan, P. A. Opioid use in chronic pain patients with chronic kidney disease: a systematic review. Pain Med. 18, 1416–1449 (2017).

    PubMed  Google Scholar 

  43. Ishida, J. H., McCulloch, C. E., Steinman, M. A., Grimes, B. A. & Johansen, K. L. Opioid analgesics and adverse outcomes among hemodialysis patients. Clin. J. Am. Soc. Nephrol. 13, 746–753 (2018).

    PubMed  PubMed Central  Google Scholar 

  44. Butler, A. M., Kshirsagar, A. V. & Brookhart, M. A. Opioid use in the US hemodialysis population. Am. J. Kidney Dis. 63, 171–173 (2014).

    PubMed  Google Scholar 

  45. Daubresse, M., Alexander, G. C., Crews, D. C., Segev, D. L. & McAdams-DeMarco, M. A. Trends in opioid prescribing among hemodialysis patients, 2007-2014. Am. J. Nephrol. 49, 20–31 (2019).

    PubMed  Google Scholar 

  46. Kimmel, P. L. et al. Opioid prescription, morbidity, and mortality in United States dialysis patients. J. Am. Soc. Nephrol. 28, 3658–3670 (2017).

    PubMed  PubMed Central  Google Scholar 

  47. Manley, H. J. et al. Factors associated with medication-related problems in ambulatory hemodialysis patients. Am. J. Kidney Dis. 41, 386–393 (2003).

    PubMed  Google Scholar 

  48. Institute of Medicine (US) Committee on Advancing Pain Research, Care and Education. Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research (The National Academies Press, 2011).

  49. Interagency Pain Research Coordinating Committee. National Pain Strategy: a comprehensive population health-level strategy for pain (IPRCC, 2016).

  50. Busse, J. W. et al. Opioids for chronic noncancer pain: a systematic review and meta-analysis. JAMA 320, 2448–2460 (2018).

    PubMed  PubMed Central  Google Scholar 

  51. Chou, R. et al. The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a National Institutes of Health Pathways to Prevention Workshop. Ann. Intern. Med. 162, 276–286 (2015).

    PubMed  Google Scholar 

  52. Roy, P. J. et al. Pain management in patients with chronic kidney disease and end-stage kidney disease. Curr. Opin. Nephrol. Hypertens. 29, 671–680 (2020).

    PubMed  PubMed Central  Google Scholar 

  53. Clive, D. M. & Clive, P. H. in Chronic Renal Disease 2nd edn Ch 65 (eds Kimmel, P. L. & Rosenberg, M. E.) 1071–1092 (Academic Press, 2019).

  54. Kienzler, J. L., Gold, M. & Nollevaux, F. Systemic bioavailability of topical diclofenac sodium gel 1% versus oral diclofenac sodium in healthy volunteers. J. Clin. Pharmacol. 50, 50–61 (2010).

    CAS  PubMed  Google Scholar 

  55. Federation of State Medical Boards. Guidelines for the chronic use of opioid analgesics (FSMB, 2017).

  56. Dowell, D., Haegerich, T. M. & Chou, R. CDC guideline for prescribing opioids for chronic pain - United States, 2016. MMWR Recomm. Rep. 65, 1–49 (2016).

    PubMed  Google Scholar 

  57. US Department of Veterans Affairs. VA/DoD clinical practice guideline for opioid therapy for chronic pain (USDVA, 2017).

  58. Wachterman, M. W. et al. One-year mortality after dialysis initiation among older adults. JAMA Intern. Med. 179, 987–990 (2019).

    PubMed  PubMed Central  Google Scholar 

  59. Clarke, H., Soneji, N., Ko, D. T., Yun, L. & Wijeysundera, D. N. Rates and risk factors for prolonged opioid use after major surgery: population based cohort study. BMJ 348, g1251 (2014).

    PubMed  PubMed Central  Google Scholar 

  60. Deyo, R. A. et al. Association between initial opioid prescribing patterns and subsequent long-term use among opioid-naive patients: a statewide retrospective cohort study. J. Gen. Intern. Med. 32, 21–27 (2017).

    PubMed  Google Scholar 

  61. Meske, D. S. et al. Efficacy of opioids versus placebo in chronic pain: a systematic review and meta-analysis of enriched enrollment randomized withdrawal trials. J. Pain Res. 11, 923–934 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Tobin, D. G., Keough Forte, K. & Johnson McGee, S. Breaking the pain contract: a better controlled-substance agreement for patients on chronic opioid therapy. Cleve Clin. J. Med. 83, 827–835 (2016).

    PubMed  Google Scholar 

  63. Bialas, P., Maier, C., Klose, P. & Hauser, W. Efficacy and harms of long-term opioid therapy in chronic non-cancer pain: systematic review and meta-analysis of open-label extension trials with a study duration ≥26 weeks. Eur. J. Pain 24, 265–278 (2020).

    PubMed  Google Scholar 

  64. Krebs, E. E. et al. Effect of opioid vs nonopioid medications on pain-related function in patients with chronic back pain or hip or knee osteoarthritis pain: the SPACE randomized clinical trial. JAMA 319, 872–882 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Vowles, K. E. et al. Rates of opioid misuse, abuse, and addiction in chronic pain: a systematic review and data synthesis. Pain 156, 569–576 (2015).

    PubMed  Google Scholar 

  66. Klimas, J. et al. Strategies to identify patient risks of prescription opioid addiction when initiating opioids for pain: a systematic review. JAMA Netw. Open 2, e193365 (2019).

    PubMed  PubMed Central  Google Scholar 

  67. Bronstein, K., Passik, S., Munitz, L. & Leider, H. Can clinicians accurately predict which patients are misusing their medications? J. Pain 12, P3 (2011).

    Google Scholar 

  68. Moore, T. M., Jones, T., Browder, J. H., Daffron, S. & Passik, S. D. A comparison of common screening methods for predicting aberrant drug-related behavior among patients receiving opioids for chronic pain management. Pain Med. 10, 1426–1433 (2009).

    PubMed  Google Scholar 

  69. Cheatle, M. D., Compton, P. A., Dhingra, L., Wasser, T. E. & O’Brien, C. P. Development of the revised opioid risk tool to predict opioid use disorder in patients with chronic nonmalignant pain. J. Pain 20, 842–851 (2019).

    PubMed  PubMed Central  Google Scholar 

  70. Paulozzi, L., Dellinger, A. & Degutis, L. Lessons from the past. Inj. Prev. 18, 70 (2012).

    PubMed  Google Scholar 

  71. Benyamin, R. et al. Opioid complications and side effects. Pain Physician 11, S105–S120 (2008).

    PubMed  Google Scholar 

  72. Wiese, A. D., Griffin, M. R., Schaffner, W., Stein, C. M. & Grijalva, C. G. Opioid analgesic use and risk for invasive pneumococcal diseases. Ann. Intern. Med. 169, 355 (2018).

    PubMed  Google Scholar 

  73. Edelman, E. J. et al. Association of prescribed opioids with increased risk of community-acquired pneumonia among patients with and without HIV. JAMA Intern. Med. 179, 297–304 (2019).

    PubMed  PubMed Central  Google Scholar 

  74. Saunders, K. W. et al. Relationship of opioid use and dosage levels to fractures in older chronic pain patients. J. Gen. Intern. Med. 25, 310–315 (2010).

    PubMed  PubMed Central  Google Scholar 

  75. Fountas, A., Van Uum, S. & Karavitaki, N. Opioid-induced endocrinopathies. Lancet Diabetes Endocrinol. 8, 68–80 (2020).

    CAS  PubMed  Google Scholar 

  76. Yi, P. & Pryzbylkowski, P. Opioid induced hyperalgesia. Pain. Med. 16 (Suppl. 1), 32–36 (2015).

    Google Scholar 

  77. Ren, Z. Y. et al. The impact of genetic variation on sensitivity to opioid analgesics in patients with postoperative pain: a systematic review and meta-analysis. Pain Physician 18, 131–152 (2015).

    PubMed  Google Scholar 

  78. Gourlay, D. L., Heit, H. A. & Almahrezi, A. Universal precautions in pain medicine: a rational approach to the treatment of chronic pain. Pain Med. 6, 107–112 (2005).

    PubMed  Google Scholar 

  79. Manchikanti, L. et al. American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic non-cancer pain: Part 2–guidance. Pain Physician 15, S67–S116 (2012).

    PubMed  Google Scholar 

  80. Chou, R. et al. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J. Pain 10, 113–130 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Centers for Disease Control and Prevention. Quality improvement and care coordination: implementing the CDC guideline for prescribing opioids for chronic pain. https://www.cdc.gov/drugoverdose/pdf/prescribing/CDC-DUIP-QualityImprovementAndCareCoordination-508.pdf (2018).

  82. McGee, S. & Silverman, R. D. Treatment agreements, informed consent, and the role of state medical boards in opioid prescribing. Pain Med. 16, 25–29 (2015).

    PubMed  Google Scholar 

  83. Buchman, D. Z. & Ho, A. What’s trust got to do with it? Revisiting opioid contracts. J. Med. Ethics 40, 673–677 (2014).

    PubMed  Google Scholar 

  84. Dunn, K. M. et al. Opioid prescriptions for chronic pain and overdose: a cohort study. Ann. Intern. Med. 152, 85–92 (2010).

    PubMed  PubMed Central  Google Scholar 

  85. Braden, J. B. et al. Emergency department visits among recipients of chronic opioid therapy. Arch. Intern. Med. 170, 1425–1432 (2010).

    PubMed  PubMed Central  Google Scholar 

  86. Bohnert, A. S. et al. Association between opioid prescribing patterns and opioid overdose-related deaths. JAMA 305, 1315–1321 (2011).

    CAS  PubMed  Google Scholar 

  87. Paulozzi, L. J. et al. A history of being prescribed controlled substances and risk of drug overdose death. Pain Med. 13, 87–95 (2012).

    PubMed  Google Scholar 

  88. Volkow, N. D. & McLellan, A. T. Opioid abuse in chronic pain — misconceptions and mitigation strategies. N. Engl. J. Med. 374, 1253–1263 (2016).

    CAS  PubMed  Google Scholar 

  89. Cassidy, T. A., DasMahapatra, P., Black, R. A., Wieman, M. S. & Butler, S. F. Changes in prevalence of prescription opioid abuse after introduction of an abuse-deterrent opioid formulation. Pain Med. 15, 440–451 (2014).

    PubMed  Google Scholar 

  90. Dasgupta, N. et al. Cohort study of the impact of high-dose opioid analgesics on overdose mortality. Pain Med. 17, 85–98 (2016).

    PubMed  Google Scholar 

  91. Hirschtritt, M. E., Olfson, M. & Kroenke, K. Balancing the risks and benefits of benzodiazepines. JAMA 325, 347–348 (2021).

    CAS  PubMed  Google Scholar 

  92. Gomes, T. et al. Gabapentin, opioids, and the risk of opioid-related death: a population-based nested case-control study. PLoS Med. 14, e1002396 (2017).

    PubMed  PubMed Central  Google Scholar 

  93. Gomes, T. et al. Pregabalin and the risk for opioid-related death: a nested case-control study. Ann. Intern. Med. 169, 732–734 (2018).

    PubMed  Google Scholar 

  94. Ruchi, R. et al. Opioid safety and concomitant benzodiazepine use in end-stage renal disease patients. Pain Res. Manag. 2019, 3865924 (2019).

    PubMed  PubMed Central  Google Scholar 

  95. Waddy, S. P. et al. Concomitant use of gabapentinoids with opioids is associated with increased mortality and morbidity among dialysis patients. Am. J. Nephrol. 51, 424–432 (2020).

    CAS  PubMed  Google Scholar 

  96. Inciardi, J. A., Surratt, H. L., Lugo, Y. & Cicero, T. J. The diversion of prescription opioid analgesics. Law Enforc. Exec. Forum 7, 127–141 (2007).

    PubMed  PubMed Central  Google Scholar 

  97. Singh, N., Fishman, S., Rich, B. & Orlowski, A. Prescription opioid forgery: reporting to law enforcement and protection of medical information. Pain Med. 14, 792–798 (2013).

    PubMed  Google Scholar 

  98. van Eeghen, C., Edwards, M., Libman, B. S., MacLean, C. D. & Kennedy, A. G. Order from chaos: an initiative to improve opioid prescribing in rheumatology using lean A3. ACR Open Rheumatol. 1, 546–551 (2019).

    PubMed  PubMed Central  Google Scholar 

  99. Longo, L. P., Parran, T., Johnson, B. & Kinsey, W. Addiction: part II. Identification and management of the drug-seeking patient. Am. Fam. Physician 61, 2401–2408 (2000).

    CAS  PubMed  Google Scholar 

  100. US Food and Drug Administration. Where and how to dispose of unused medicines. https://www.fda.gov/consumers/consumer-updates/where-and-how-dispose-unused-medicines (2021).

  101. Lea-Henry, T. N., Carland, J. E., Stocker, S. L., Sevastos, J. & Roberts, D. M. Clinical pharmacokinetics in kidney disease. Clin. J. Am. Soc. Nephrol. 13, 1085–1095 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Déri, M. T. et al. End-stage renal disease reduces the expression of drug-metabolizing cytochrome P450s. Pharmacol. Rep. 72, 1695–1705 (2020).

    PubMed  PubMed Central  Google Scholar 

  103. Dreisbach, A. W. & Lertora, J. J. L. The effect of chronic renal failure on drug metabolism and transport. Expert. Opin. Drug Metab. Toxicol. 4, 1065–1074 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Davison, S. N. Clinical pharmacology considerations in pain management in patients with advanced kidney failure. Clin. J. Am. Soc. Nephrol. 14, 917–931 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  105. King, S., Forbes, K., Hanks, G. W., Ferro, C. J. & Chambers, E. J. A systematic review of the use of opioid medication for those with moderate to severe cancer pain and renal impairment: a European Palliative Care Research Collaborative opioid guidelines project. Palliat. Med. 25, 525–552 (2011).

    CAS  PubMed  Google Scholar 

  106. Paglialunga, S., Offman, E., Ichhpurani, N., Marbury, T. C. & Morimoto, B. H. Update and trends on pharmacokinetic studies in patients with impaired renal function: practical insight into application of the FDA and EMA guidelines. Expert. Rev. Clin. Pharmacol. 10, 273–283 (2017).

    CAS  PubMed  Google Scholar 

  107. Goedel, W. C. et al. Association of racial/ethnic segregation with treatment capacity for opioid use disorder in counties in the United States. JAMA Netw. Open 3, e203711 (2020).

    PubMed  PubMed Central  Google Scholar 

  108. Hansen, H., Siegel, C., Wanderling, J. & DiRocco, D. Buprenorphine and methadone treatment for opioid dependence by income, ethnicity and race of neighborhoods in New York City. Drug Alcohol. Depend. 164, 14–21 (2016).

    PubMed  PubMed Central  Google Scholar 

  109. Schuckit, M. A. Treatment of opioid-use disorders. N. Engl. J. Med. 375, 357–368 (2016).

    PubMed  Google Scholar 

  110. Davis, M. P., Pasternak, G. & Behm, B. Treating chronic pain: an overview of clinical studies centered on the buprenorphine option. Drugs 78, 1211–1228 (2018).

    PubMed  PubMed Central  Google Scholar 

  111. Daitch, J. et al. Conversion of chronic pain patients from full-opioid agonists to sublingual buprenorphine. Pain Physician 15, ES59–ES66 (2012).

    PubMed  Google Scholar 

  112. Daitch, D. et al. Conversion from high-dose full-opioid agonists to sublingual buprenorphine reduces pain scores and improves quality of life for chronic pain patients. Pain Med. 15, 2087–2094 (2014).

    PubMed  Google Scholar 

  113. Malinoff, H. L., Barkin, R. L. & Wilson, G. Sublingual buprenorphine is effective in the treatment of chronic pain syndrome. Am. J. Ther. 12, 379–384 (2005).

    PubMed  Google Scholar 

  114. Sorge, J. & Sittl, R. Transdermal buprenorphine in the treatment of chronic pain: results of a phase III, multicenter, randomized, double-blind, placebo-controlled study. Clin. Ther. 26, 1808–1820 (2004).

    CAS  PubMed  Google Scholar 

  115. Center for Substance Abuse Treatment. Clinical guidelines for the use of buprenorphine in the treatment of opioid addiction (Substance Abuse and Mental Health Services Administration, 2004).

  116. Harris, S. C., Morganroth, J., Ripa, S. R., Thorn, M. D. & Colucci, S. Effects of buprenorphine on QT intervals in healthy subjects: results of 2 randomized positive- and placebo-controlled trials. Postgrad. Med. 129, 69–80 (2017).

    PubMed  Google Scholar 

  117. Kao, D. P., Haigney, M. C., Mehler, P. S. & Krantz, M. J. Arrhythmia associated with buprenorphine and methadone reported to the Food and Drug Administration. Addiction 110, 1468–1475 (2015).

    PubMed  PubMed Central  Google Scholar 

  118. Volpe, D. A. et al. Uniform assessment and ranking of opioid μ receptor binding constants for selected opioid drugs. Regul. Toxicol. Pharmacol. 59, 385–390 (2011).

    CAS  PubMed  Google Scholar 

  119. Becker, W. C., Frank, J. W. & Edens, E. L. Switching from high-dose, long-term opioids to buprenorphine: a case series. Ann. Intern. Med. 173, 70–71 (2020).

    PubMed  Google Scholar 

  120. Ghosh, S. M., Klaire, S., Tanguay, R., Manek, M. & Azar, P. A review of novel methods to support the transition from methadone and other full agonist opioids to buprenorphine/naloxone sublingual in both community and acute care settings. Can. J. Addict. 10, 41–50 (2019).

    Google Scholar 

  121. Filitz, J. et al. Effects of intermittent hemodialysis on buprenorphine and norbuprenorphine plasma concentrations in chronic pain patients treated with transdermal buprenorphine. Eur. J. Pain 10, 743–748 (2006).

    CAS  PubMed  Google Scholar 

  122. Elkader, A. & Sproule, B. Buprenorphine: clinical pharmacokinetics in the treatment of opioid dependence. Clin. Pharmacokinet. 44, 661–680 (2005).

    CAS  PubMed  Google Scholar 

  123. Salili, A. R., Muller, D., Skendaj, R., Jehle, A. W. & Taegtmeyer, A. B. Breakthrough pain associated with a reduction in serum buprenorphine concentration during dialysis. Clin. Ther. 38, 212–215 (2016).

    CAS  PubMed  Google Scholar 

  124. Substance Abuse and Mental Health Services Administration. Medications for opioid use disorder. Treatment Improvement Protocol: TIP 63 (SAMHSA, 2021).

  125. Becker, W. C. et al. Evaluation of an integrated, multidisciplinary program to address unsafe use of opioids prescribed for pain. Pain Med. 19, 1419–1424 (2018).

    PubMed  Google Scholar 

  126. Jannetto, P. J. & Langman, L. J. Using clinical laboratory tests to monitor drug therapy in pain management patients. J. Appl. Lab. Med. 2, 471–472 (2019).

    Google Scholar 

  127. Argoff, C. E. et al. Rational urine drug monitoring in patients receiving opioids for chronic pain: consensus recommendations. Pain Med. 19, 97–117 (2018).

    PubMed  Google Scholar 

  128. Tobin, D. G. A rational approach to opioid use disorder in primary care. Cleve Clin. J. Med. 84, 385–387 (2017).

    PubMed  Google Scholar 

  129. Substance Abuse and Mental Health Services Administration. Federal guidelines for opioid treatment programs (SAMHSA, 2015).

  130. Ward, M. B., Hackenmueller, S. A. & Strathmann, F. G. for the Education Committee of the Academy of Clinical Laboratory Physicians and Scientists. Pathology consultation on urine compliance testing and drug abuse screening. Am. J. Clin. Pathol. 142, 586–593 (2014).

    PubMed  Google Scholar 

  131. Kluge, J., Rentzsch, L., Remane, D., Peters, F. T. & Wissenbach, D. K. Systematic investigations of novel validity parameters in urine drug testing and prevalence of urine adulteration in a two-year cohort. Drug Test. Anal. 10, 1536–1542 (2018).

    CAS  PubMed  Google Scholar 

  132. Allen, K. R. Screening for drugs of abuse: which matrix, oral fluid or urine? Ann. Clin. Biochem. 48, 531–541 (2011).

    CAS  PubMed  Google Scholar 

  133. Honarmand, M., Farhad-Mollashahi, L., Nakhaee, A. & Sargolzaie, F. Oral manifestation and salivary changes in renal patients undergoing hemodialysis. J. Clin. Exp. Dent. 9, e207–e210 (2017).

    PubMed  PubMed Central  Google Scholar 

  134. Chiu, Y. W. et al. Pill burden, adherence, hyperphosphatemia, and quality of life in maintenance dialysis patients. Clin. J. Am. Soc. Nephrol. 4, 1089–1096 (2009).

    PubMed  PubMed Central  Google Scholar 

  135. Park, H. et al. Adherence and persistence to prescribed medication therapy among Medicare part D beneficiaries on dialysis: comparisons of benefit type and benefit phase. J. Manag. Care Spec. Pharm. 20, 862–876 (2014).

    PubMed  Google Scholar 

  136. St. Peter, W. L. Management of polypharmacy in dialysis patients. Semin. Dialysis 28, 427–432 (2015).

    Google Scholar 

  137. Pai, A. B. et al. Medication reconciliation and therapy management in dialysis-dependent patients: need for a systematic approach. Clin. J. Am. Soc. Nephrol. 8, 1988–1999 (2013).

    PubMed  PubMed Central  Google Scholar 

  138. Kaplan, B., Mason, N. A., Shimp, L. A. & Ascione, F. J. Chronic hemodialysis patients. Part I: characterization and drug-related problems. Ann. Pharmacother. 28, 316–319 (1994).

    CAS  PubMed  Google Scholar 

  139. Nakhaee, S. et al. Tramadol and the occurrence of seizures: a systematic review and meta-analysis. Crit. Rev. Toxicol. 49, 710–723 (2019).

    CAS  PubMed  Google Scholar 

  140. Hanes, S. D., Franklin, M., Kuhl, D. A. & Headley, A. S. Prolonged opioid antagonism with naloxone in chronic renal failure. Pharmacotherapy 19, 897–901 (1999).

    CAS  PubMed  Google Scholar 

  141. Sohn, M., Talbert, J. C., Huang, Z., Lofwall, M. R. & Freeman, P. R. Association of naloxone coprescription laws with naloxone prescription dispensing in the United States. JAMA Netw. Open 2, e196215 (2019).

    PubMed  PubMed Central  Google Scholar 

  142. Guy, G. P. Jr et al. Vital signs: pharmacy-based naloxone dispensing–United States, 2012–2018. MMWR Morb. Mortal. Wkly. Rep. 68, 679–686 (2019).

    PubMed  PubMed Central  Google Scholar 

  143. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5™ 5th ed (American Psychiatric Publishing, 2013).

  144. Banta-Green, C. J. et al. The Prescribed Opioids Difficulties Scale: a patient-centered assessment of problems and concerns. Clin. J. Pain. 26, 489–497 (2010).

    PubMed  PubMed Central  Google Scholar 

  145. Tobin, D. G., Andrews, R. & Becker, W. C. Prescribing opioids in primary care: safely starting, monitoring, and stopping. Cleve Clin. J. Med. 83, 207–215 (2016).

    PubMed  Google Scholar 

  146. Bruneau, J. et al. Management of opioid use disorders: a national clinical practice guideline. CMAJ 190, E247–E257 (2018).

    PubMed  PubMed Central  Google Scholar 

  147. Kampman, K. & Jarvis, M. American Society of Addiction Medicine (ASAM) National Practice Guideline for the use of medications in the treatment of addiction involving opioid use. J. Addict. Med. 9, 358–367 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  148. European Monitoring Centre for Drugs and Drug Addiction. Health and social responses to drug problems: a European guide (Publications Office of the European Union, 2017).

  149. Zhan, M. et al. Association of opioids and nonsteroidal anti-inflammatory drugs with outcomes in CKD: findings from the CRIC (Chronic Renal Insufficiency Cohort) study. Am. J. Kidney Dis. 76, 184–193 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  150. Jaffe, J. A. & Kimmel, P. L. Chronic nephropathies of cocaine and heroin abuse: a critical review. Clin. J. Am. Soc. Nephrol. 1, 655–667 (2006).

    CAS  PubMed  Google Scholar 

  151. Konstantinidis, I. et al. Representation of patients with kidney disease in trials of cardiovascular interventions: an updated systematic review. JAMA Intern. Med. 176, 121–124 (2016).

    PubMed  Google Scholar 

  152. Kitchlu, A. et al. Representation of patients with chronic kidney disease in trials of cancer therapy. JAMA 319, 2437–2439 (2018).

    PubMed  PubMed Central  Google Scholar 

  153. US Food and Drug Administration. Enhancing the diversity of clinical trial populations — eligibility criteria, enrollment practices, and trial designs guidance for industry. https://www.fda.gov/media/127712/download (2020).

  154. US Food and Drug Administration. Guidance for industry: pharmacokinetics in patients with impaired renal function–study design, data analysis, and impact on dosing. https://www.fda.gov/media/78573/download (2020).

  155. Agarwal, D., Udoji, M. A. & Trescot, A. Genetic testing for opioid pain management: a primer. Pain. Ther. 6, 93–105 (2017).

    PubMed  PubMed Central  Google Scholar 

  156. Ettienne, E. B. et al. Pharmacogenomics-guided policy in opioid use disorder (OUD) management: an ethnically-diverse case-based approach. Addict. Behav. Rep. 6, 8–14 (2017).

    PubMed  PubMed Central  Google Scholar 

  157. Kapur, B. M., Lala, P. K. & Shaw, J. L. Pharmacogenetics of chronic pain management. Clin. Biochem. 47, 1169–1187 (2014).

    CAS  PubMed  Google Scholar 

  158. Raouf, M., Bettinger, J., Wegrzyn, E. W., Mathew, R. O. & Fudin, J. J. Pharmacotherapeutic management of neuropathic pain in end-stage renal disease. Kidney Dis. 6, 157–167 (2020).

    Google Scholar 

  159. He, X., Fan, L., Wu, Z., He, J. & Cheng, B. Gene expression profiles reveal key pathways and genes associated with neuropathic pain in patients with spinal cord injury. Mol. Med. Rep. 15, 2120–2128 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  160. Descalzi, G. et al. Neuropathic pain promotes adaptive changes in gene expression in brain networks involved in stress and depression. Sci. Signal. 10, eaaj1549 (2017).

    PubMed  PubMed Central  Google Scholar 

  161. Minerbi, A. et al. Altered microbiome composition in individuals with fibromyalgia. Pain 160, 2589–2602 (2019).

    CAS  PubMed  Google Scholar 

  162. Martin, C. R., Osadchiy, V., Kalani, A. & Mayer, E. A. The brain-gut-microbiome axis. Cell Mol. Gastroenterol. Hepatol. 6, 133–148 (2018).

    PubMed  PubMed Central  Google Scholar 

  163. Dworsky-Fried, Z., Kerr, B. J. & Taylor, A. M. W. Microbes, microglia, and pain. Neurobiol. Pain 7, 100045–100045 (2020).

    PubMed  PubMed Central  Google Scholar 

  164. Kaye, A. D. et al. Update on the pharmacogenomics of pain management. Pharmgenomics Pers. Med. 12, 125–143 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  165. Ruano, G. & Kost, J. A. Fundamental considerations for genetically-guided pain management with opioids based on CYP2D6 and OPRM1 polymorphisms. Pain Physician 21, E611–E621 (2018).

    PubMed  Google Scholar 

  166. Molanaei, H. et al. Influence of the CYP2D6 polymorphism and hemodialysis on codeine disposition in patients with end-stage renal disease. Eur. J. Clin. Pharmacol. 66, 269–273 (2010).

    CAS  PubMed  Google Scholar 

  167. Guay, D. R. et al. Pharmacokinetics and pharmacodynamics of codeine in end-stage renal disease. Clin. Pharmacol. Ther. 43, 63–71 (1988).

    CAS  PubMed  Google Scholar 

  168. Koehntop, D. E. & Rodman, J. H. Fentanyl pharmacokinetics in patients undergoing renal transplantation. Pharmacotherapy 17, 746–752 (1997).

    CAS  PubMed  Google Scholar 

  169. Joh, J., Sila, M. K. & Bastani, B. Nondialyzability of fentanyl with high-efficiency and high-flux membranes. Anesth. Analg. 86, 447 (1998).

    CAS  PubMed  Google Scholar 

  170. Bastani, B. & Jamal, J. A. Removal of morphine but not fentanyl during haemodialysis. Nephrol. Dial. Transpl. 12, 2802–2804 (1997).

    CAS  Google Scholar 

  171. Darwish, M., Yang, R., Tracewell, W., Robertson, P. Jr & Bond, M. Effects of renal impairment and hepatic impairment on the pharmacokinetics of hydrocodone after administration of a hydrocodone extended-release tablet formulated with abuse-deterrence technology. Clin. Pharmacol. Drug Dev. 5, 141–149 (2016).

    CAS  PubMed  Google Scholar 

  172. Perlman, R. et al. Intradialytic clearance of opioids: methadone versus hydromorphone. Pain 154, 2794–2800 (2013).

    CAS  PubMed  Google Scholar 

  173. Lee, M. A., Leng, M. E. & Tiernan, E. J. Retrospective study of the use of hydromorphone in palliative care patients with normal and abnormal urea and creatinine. Palliat. Med. 15, 26–34 (2001).

    CAS  PubMed  Google Scholar 

  174. Davison, S. N. & Mayo, P. R. Pain management in chronic kidney disease: the pharmacokinetics and pharmacodynamics of hydromorphone and hydromorphone-3-glucuronide in hemodialysis patients. J. Opioid Manag. 4, 335–344 (2008).

    PubMed  Google Scholar 

  175. Hsu, C. H., Lin, T. C., Lu, C. C., Lin, S. H. & Ho, S. T. Clearance of meperidine and its metabolite normeperidine in hemodialysis patients with chronic noncancer pain. J. Pain Symptom Manage 47, 801–805 (2014).

    PubMed  Google Scholar 

  176. Hassan, H., Bastani, B. & Gellens, M. Successful treatment of normeperidine neurotoxicity by hemodialysis. Am. J. Kidney Dis. 35, 146–149 (2000).

    CAS  PubMed  Google Scholar 

  177. Opdal, M. S. et al. Effects of hemodialysis on methadone pharmacokinetics and QTc. Clin. Ther. 37, 1594–1599 (2015).

    CAS  PubMed  Google Scholar 

  178. Kreek, M. J., Schecter, A. J., Gutjahr, C. L. & Hecht, M. Methadone use in patients with chronic renal disease. Drug Alcohol. Depend. 5, 197–205 (1980).

    CAS  PubMed  Google Scholar 

  179. Furlan, V. et al. Methadone is poorly removed by haemodialysis. Nephrol. Dial. Transpl. 14, 254–255 (1999).

    CAS  Google Scholar 

  180. Dean, M. Opioids in renal failure and dialysis patients. J. Pain. Symptom Manage 28, 497–504 (2004).

    CAS  PubMed  Google Scholar 

  181. Osborne, R., Joel, S., Grebenik, K., Trew, D. & Slevin, M. The pharmacokinetics of morphine and morphine glucuronides in kidney failure. Clin. Pharmacol. Ther. 54, 158–167 (1993).

    CAS  PubMed  Google Scholar 

  182. O’Connor, N. R. & Corcoran, A. M. End-stage renal disease: symptom management and advance care planning. Am. Fam. Physician 85, 705–710 (2012).

    PubMed  Google Scholar 

  183. Smith, H. S. Opioid metabolism. Mayo Clin. Proc. 84, 613–624 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  184. Leuppi-Taegtmeyer, A. et al. Pharmacokinetics of oxycodone/naloxone and its metabolites in patients with end-stage renal disease during and between haemodialysis sessions. Nephrol. Dial. Transpl. 34, 692–702 (2019).

    CAS  Google Scholar 

  185. Samolsky Dekel, B. G. et al. Dialyzability of oxycodone and its metabolites in chronic noncancer pain patients with end-stage renal disease. Pain. Pract. 17, 604–615 (2017).

    PubMed  Google Scholar 

  186. Kirvela, M., Lindgren, L., Seppala, T. & Olkkola, K. T. The pharmacokinetics of oxycodone in uremic patients undergoing renal transplantation. J. Clin. Anesth. 8, 13–18 (1996).

    CAS  PubMed  Google Scholar 

  187. Pham, P. C. et al. 2017 update on pain management in patients with chronic kidney disease. Clin. Kidney J. 10, 688–697 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  188. Izzedine, H. et al. Pharmacokinetics of tramadol in a hemodialysis patient. Nephron 92, 755–756 (2002).

    PubMed  Google Scholar 

  189. Vardanyan, R. S. & Hruby, V. J. Fentanyl-related compounds and derivatives: current status and future prospects for pharmaceutical applications. Future Med. Chem. 6, 385–412 (2014).

    CAS  PubMed  Google Scholar 

  190. Paramanandam, G., Prommer, E. & Schwenke, D. C. Adverse effects in hospice patients with chronic kidney disease receiving hydromorphone. J. Palliat. Med. 14, 1029–1033 (2011).

    PubMed  Google Scholar 

  191. Aiyer, R., Mehta, N., Gungor, S. & Gulati, A. A systematic review of NMDA receptor antagonists for treatment of neuropathic pain in clinical practice. Clin. J. Pain 34, 450–467 (2018).

    PubMed  Google Scholar 

  192. Chou, R. et al. Methadone safety: a clinical practice guideline from the American Pain Society and College on Problems of Drug Dependence, in collaboration with the Heart Rhythm Society. J. Pain 15, 321–337 (2014).

    CAS  PubMed  Google Scholar 

  193. Grond, S. & Sablotzki, A. Clinical pharmacology of tramadol. Clin. Pharmacokinet. 43, 879–923 (2004).

    CAS  PubMed  Google Scholar 

  194. [No authors listed] Transdermal buprenorphine (Butrans) for chronic pain. Med. Lett. Drugs Ther. 53, 31–32 (2011).

    Google Scholar 

  195. US Food and Drug Administration. Highlights of prescribing information: Butrans. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021306s015s019lbl.pdf (2014).

  196. [No authors listed] Buprenorphine buccal film (Belbuca) for chronic pain. Med. Lett. Drugs Ther. 58, 47–48 (2016).

    Google Scholar 

  197. Chou, R., Ballantyne, J. & Lembke, A. Rethinking opioid dose tapering, prescription opioid dependence, and indications for buprenorphine. Ann. Intern. Med. 171, 427–429 (2019).

    PubMed  Google Scholar 

  198. Heit, H. A., Covington, E. & Good, P. M. Dear DEA. Pain. Med. 5, 303–308 (2004).

    PubMed  Google Scholar 

Download references

Acknowledgements

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.

Author information

Authors and Affiliations

Authors

Consortia

Contributions

All authors researched data for the article, made substantial contributions to discussions of the content and wrote, reviewed or edited the manuscript before submission.

Corresponding author

Correspondence to Daniel G. Tobin.

Ethics declarations

Competing interests

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.

Additional information

Peer review information

Nature Reviews Nephrology thanks M. Bair, I. Istampoulouoglou, A. Leuppi-Taegtmeyer and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Related links

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/

PDMP: https://www.pdmpassist.org/

Risk Evaluation and Mitigation Strategies courses: https://search.opioidanalgesicrems.com/RPC-RMS-PROD/Guest/GuestPageExternal.aspx

Supplementary information

Glossary

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.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41581-021-00484-6

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing