Chronic use of opioids (COU) before kidney transplantation may be associated with an increased risk of early graft loss and higher mortality after transplant, according to a retrospective study from the University of Michigan presented at the American Transplant Congress in Philadelphia in May.
Of the 1064 adult patients who received a kidney graft at the university between 2004 and 2008, 42.5 percent reported that they had chronic pain and 10.2 percent reported that they had used opioids on a chronic basis before their transplants. The patients were followed up until the end of 2010. These figures are in line with published reports showing that 50 percent of patients with ESRD report some degree of chronic pain, and 5–36 percent use opioid analgesics on a chronic basis, said Fidel Barrantes, MD, clinical transplant fellow at the University of Michigan. Barrantes spoke at the session Painful Consequences: Chronic Use of Prescription Opioids Is Associated with Adverse Kidney Transplant Outcomes.
“Four types of opioids were used in more than 90 percent of this population,” Barrantes reported. Forty-four percent used hydrocodone, 17 percent propoxyphene, 15 percent oxycodone, and 14 percent tramadol. The most common pain was neuropathic (53 percent of patients), followed by limb pain (39 percent), lower back (16 percent), headache, abdominal, and other pains.
The COU group, comprising 108 patients, had more African Americans than did the non-COU group (25 percent versus 17.5 percent, respectively) and had more comorbidities, double the rate of alcohol abuse (18.5 percent versus 9.9 percent), more illicit drug abuse (20.4 percent versus 11.1 percent), a more positive psychiatric history (51.9 percent versus 27.8 percent), and three times the rate of use of nonopioid analgesics (26.9 percent versus 8.2 percent).
The non-COU group included more employed patients (44.1 percent versus 18.5 percent) and more patients with private insurance (43.8 percent versus 30.6 percent).
The two groups did not differ significantly in terms of age (approximately 50 years), gender (approximately 60 percent male), body mass index (approximately 28.5 kg/m2), proportion with diabetes, or length of time receiving dialysis.
“Pretransplant chronic opioid use is associated with worse patient survival at 1, 3, and 5 years,” Barrantes said, with significant differences in survival between the COU and non-COU groups at 3 and 5 years. The death rates at 3 years were 18 percent for the COU group and 7.5 percent for the non-COU group. At 5 years, death rates were 21 percent versus 12 percent, respectively (p = 0.026).
Reported chronic opioid use before transplant was associated with a 66 percent increased risk of death after transplant, according to a multivariate model. This risk was higher than even for the presence of diabetes before transplant, which conferred a 42 percent increased risk. Receipt of a kidney from a living donor lowered the risk of death after transplant by half.
Graft loss was significantly increased by COU only at the 1-year point in comparison with the non-COU group (5.5 percent versus 1.5 percent, respectively). At 3 years, graft loss was in the range of 4.5–6.5 percent and was around 7–7.5 percent at 5 years. These latter differences were not statistically significant between the COU and non-COU groups.
In the first year after transplant, COU emerged as the major predictor of graft loss. When compared with non-COU, COU conferred almost a threefold increased risk of graft loss (hazard ratio = 2.90). Current smoking was associated with a more than twofold increased risk (hazard ratio = 2.63).
A much smaller study by Walczak and colleagues also presented at the conference again showed that cigarette smoking (n = 9) was associated with a nonsignificant trend toward lower graft survival at 3 and 5 years after transplant, as was alcohol use.
Barrantes noted that his study was retrospective, depended on self-reported use of pain medication, and lacked information on opioid use after transplant—all limitations of the study.
Speaking with ASN Kidney News, he said that because the study was retrospective and based on self-reports, it was impossible to discern the reasons for opioid use, leaving open the possibility that patients used the drugs to treat painful conditions, such as diabetes or vascular conditions, that in themselves could affect patient or graft survival.
Barrantes cautioned that the study should not be interpreted to disqualify COU patents from consideration for transplants. However, clinicians should be vigilant to identify such patients and to target them for follow-up by social workers and possibly psychologists, particularly in the first year after transplant.