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.

Fig. 1 |. Factors contributing to altered pharmacokinetics in patients with hDKF.

Kidney failure and dialysis treatment can impact pharmacokinetics, which might change drug responses. For parent drugs and/or metabolites that are typically eliminated in the kidneys, reduced renal clearance in patients with haemodialysis-dependent kidney failure (HDKF) can potentially lead to drug and/or metabolite accumulation and increased systemic exposure. Hepatic drug metabolism and drug transporter activity are similarly decreased in patients with HDKF, which can additionally impair non-renal clearance^–. Although the net effects of HDKF and altered non-renal clearance on opioid disposition are complex, accumulation of drug substrates and increased systemic exposure is likely in these patients. Concurrent use of medications that inhibit or induce the activity of drug-metabolizing enzymes further complicate opioid management in patients with HDKF. CYP, cytochrome P450; OATPs, organic anion-transporting polypeptides; P-gp, P-glycopr otein.