Chronic Opioid Use Shortens Kidney Transplant Survival

Daniel M. Keller, PhD

June 07, 2011

June 7, 2011 (Philadelphia, Pennsylvania) — Self-reported chronic opioid use (COU) before kidney transplantation is associated with an increased risk for early graft loss and higher mortality posttransplant, according to a retrospective study from the University of Michigan, Ann Arbor, presented here at the American Transplant Congress (ATC) 2011.

Fidel Barrantes, MD, clinical transplant fellow at the University of Michigan, told meeting attendees that of the 1064 adult patients who received a kidney graft at the university between 2004 and 2008 and who were followed until the end of 2010, 42.5% reported chronic pain and 10.2% reported COU in the pretransplant period.

He said that these figures are in line with the literature showing that 50% of patients with end-stage renal disease report some degree of chronic pain, and that 5% to 36% use opioid analgesics on a chronic basis.

"Four types of opioids were used in more than 90% of this population," Dr. Barrantes reported; 44% used hydrocodone, 17% used propoxyphene, 15% used oxycodone, and 14% used tramadol. The most common pain was neuropathic (53% of patients), followed by limb pain (39%), lower back pain (16%), headache, abdominal pain, and other pains.

The COU group (n = 108) had higher comorbidity scores (P < .001), double the rate of alcohol abuse (18.5% vs 9.9%; P = .006), and more illicit drug abuse (20.4% vs 11.1%; P < .001) than the non-COU group (n = 956). More people in the COU group had a positive psychiatric history (51.9% vs 27.8%; P < .001), and the COU group had 3 times the rate of use of nonopioid analgesics (26.9% vs 8.2%; P = .017).

The non-COU group contained more people who were employed (44.1% vs 18.5%; P < .001) and more people with private insurance (43.8% vs 30.6%; P = .008).

There were more African Americans in the COU group than in the non-COU group (25% vs 17.5%; P = .05).

The COU group and the non-COU group did not differ significantly in terms of age (average, 51.3 vs 49.2 years), sex (58.3% vs 63.3% men), body mass index (28.6 vs 28.4 kg/m2), proportion with diabetes, or length of time on dialysis.

Results

"Pretransplant chronic opioid use is associated with worse patient survival at 1, 3, and 5 years," Dr. Barrantes said, with significant differences in survival between the COU and non-COU groups at 3 and 5 years. The death rates were higher in the COU group at 3 years (18% vs 7.5%; P = .001) and at 5 years (21% vs 12%; P = .026).

In a multivariate model of predictors of mortality, COU was associated with a 66% increase in risk for mortality (hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.05 to 2.62; P = .03). This risk was higher than even the presence of diabetes pretransplantation (HR, 1.42; P = .076). The risk was lower with a living donor kidney (HR, 0.50; 95% CI, 0.33 to 0.74; P = .001).

In contrast to patient survival, death-censored graft survival was significantly diminished with COU only at 1 year. Graft loss was about 5.5% with COU and 1.5% with non-COU at 1 year (P = .005). Graft loss was in the 4.5% to 6.5% range at 3 years and at around 7.0% to 7.5% at 5 years; the differences between the 2 groups were nonsignificant.

When predictors of death-censored graft loss were calculated, COU emerged as the major predictor in the first year after transplantation, with an HR of 2.90 (95% CI, 1.10 to 7.64; P = .031). Current smoking also conferred more than a 2-fold risk (HR, 2.63; P = .002).

A much smaller study, conducted at the University of Chicago, Illinois, by Debra A. Walczak, BSN, and colleagues, was presented at the ATC meeting. Those researchers found that cigarette smoking (n = 9) and alcohol use (n = 22) were associated with a nonsignificant trend toward lower graft survival at 3 and 5 years.

Dr. Barrantes noted that the limitations of the study his team conducted were that it was retrospective, depended on self-reported use of pain medication, and lacked information on opioid use posttransplantation.

In speaking with Medscape Medical News, Dr. Barrantes said that it was not possible to know the specific reasons in each case for opioid use because the study was retrospective. Therefore, he said, the possibility exists that opioid use could be a marker for other morbidities (e.g., diabetes or vascular conditions causing pain) that affect patient or graft survival. Although the multivariate model was designed to adjust for such variables, it might not have eliminated all possibility of their influencing the observed outcomes.

He emphasized that this study should not be interpreted as disqualifying COU patents from consideration for transplantation, but it points to the need for special screenings to identify them early on and to implement targeted follow-up by social workers, and possibly psychologists, especially in the first year after transplantation.

Session moderator James Chon, MD, a transplant nephrologist and assistant professor of medicine at the University of Chicago, who was not involved with the study, said that this investigation is preliminary, and more detail is needed to determine whether it is the opioid use itself or other related factors that contribute to the increased mortality.

"History of pain medication use, whether in the past or active use, does raise a red flag. Being able to monitor these patients closely for compliance or adherence, I think, is very important," Dr. Chon said.

Dr. Barrantes and Dr. Chon have disclosed no relevant financial relationships.

American Transplant Congress (ATC) 2011: Concurrent session 25. Presented May 3, 2011.

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