Donor kidneys categorized as high-risk by the Centers for Disease Control and Prevention (CDC) had a low viral transmission risk and good graft function at about one year of follow-up, according to a new prospective study published in Archives of Surgery (2011;146:1261-1266).
“The actual risk of viral transmission through transplant of CDC high-risk [CDCHR] organs is not known,” said senior author Andrew L. Singer, MD, PhD, Assistant Professor of Surgery at the Johns Hopkins University School of Medicine. Given that this risk has not been quantified, patients and transplant providers have been reluctant to use these organs, he added.
The just-published research sought to provide more information.
“Recipients of these organs were tested at multiple times in the year after transplant, which is the first step in quantifying the actual infectious threat,” Dr. Singer said. By testing the viral status of recipients at surgery and serially posttransplant, researchers will eventually have a big enough sample size to make informed decisions about risk, he added.
This study is more rigorous than many others that have looked at CDC high-risk organs, commented Richard B. Freeman Jr., MD, Chair of the Department of Surgery at Dartmouth-Hitchcock Medical Center. However, while the paper was provocative, it did not include enough patients to reach definitive conclusions, he added.
Bonnie E. Lonze, MD, PhD, of the Division of Transplant Surgery at Johns Hopkins University School of Medicine, was the lead author.
Serial Viral Testing
Dr. Singer and colleagues conducted a single-center, longitudinal, observational study of 50 patients, 18 years and older, who received a CDC high-risk donor kidney between Sept. 1, 2008, and Jan. 31, 2010, at the Johns Hopkins Hospital. Outcomes of the recipients of a high-risk kidney were then compared with those of 125 non-high-risk recipients who were transplanted at Johns Hopkins Hospital during the same time period. Preliminary study results were presented at the American Society of Transplant Surgeons 10th Annual State of the Art Winter Symposium in January 2010.
As part of the standard workup, all transplant candidates were screened with enzyme-linked immunosorbent assay (ELISA) testing for HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV). All CDC high-risk donors underwent nucleic acid testing (NAT) for the three viruses before transplant. Recipient baseline NAT for these viruses was obtained on the day of the transplant.
At one, three, six, and 12 months posttransplant, recipients of CDC high-risk kidneys underwent ELISA testing for HIV, HBV surface antigen, and HCV antibody, as well as NAT for HIV, hepatitis B, and hepatitis C.
NAT testing “is not standard across the country right now,” Dr. Freeman said. However, it is more sophisticated than routine serologic testing and detects viral presence at an earlier stage of infection, he explained.
“NAT adds to the level of safety we can provide to our transplant recipients,” noted Jay A. Fishman, MD, Associate Director of the Massachusetts General Hospital (MGH) Transplant Center, Director of the Transplant Infectious Diseases & Compromised Host Program at MGH, and Professor of Medicine at Harvard Medical School.
Additionally, with informed consent, NAT can potentially allow for the use of organs from donors who might have previously been excluded based on being categorized as high risk, he wrote in an email to Nephrology Times.
Universal nucleic acid testing, which was recently recommended by a proposed guideline from the CDC (www.regulations.gov/#!documentDetail;D=CDC-2011-0011-0001 ), is a controversial topic in transplantation, as access to such tests, the tight time frames within which transplants must occur, and other logistical hurdles can pose challenges.
In 2010, consensus conference participants reported insufficient evidence to recommend routine NAT for HIV, hepatitis C, and hepatitis B in donors with no identified risk factors (Am J Transplantation 10:889–899). For donors with identified behavioral risk factors, NAT should be considered to reduce the risk of transmission and increase organ utilization, they reported.
One drawback of NAT is that it's associated with a higher rate of false positives than serologic testing is, Dr. Freeman said.
Transmitting a virus based on a false-negative serologic test in the donor is “extremely rare,” he added. “So is it worth it to spend extra money on a NAT test, which may have a false positive result more often than a serologic test is falsely negative?” he said.
In the study by Dr. Singer and colleagues, NAT indicated no organ recipient seroconversion over a median follow-up period of 11.3 months. Median creatinine levels at one year were the same in each group—1.4 mg/dL.
Patients who accepted CDC high-risk kidneys had a significantly shorter median waiting list time compared with recipients of non-high-risk kidneys—274 days and 736 days, respectively.
NAT showed all donors to be HIV negative. In terms of hepatitis C, 18.0% of CDC high-risk donors were HVC positive, compared with 7.2% of non-high-risk donors. Regarding HBV, 16.7% of CDC high-risk donors were hepatitis B core antibody positive, versus 9.6% of non-high-risk donors.
CDC high-risk donors were significantly younger than non-high-risk donors, with mean ages of 35 and 43, respectively. Additionally, a significantly smaller proportion of CDC high-risk donors were expanded-criteria donors (2.0% vs 24.8%) or had a terminal creatinine level exceeding 2.5 mg/dL (4.0% vs 8.8%).
Generally, CDC high-risk kidneys are more likely to be high quality because the donors are often younger and healthier than average donors, despite high-risk behaviors, Dr. Singer noted. In the study, intravenous drug use was the most common high-risk behavior among the high-risk donors. Being incarcerated at the time of death, having sex with a high-risk partner, or being a sex worker were some of the others.
Patients were counseled about the potential risks and benefits of receiving CDC high-risk kidneys and assessed for their willingness to accept these organs.
In addition to undergoing the United Network for Organ Sharing (UNOS) special informed consent for transplantation of a CDC high-risk organ and a consent approved by the Johns Hopkins Institutional Review Board, Dr. Singer's patients are counseled in explicit terms about the high-risk behaviors of their potential donors.
Counseling starts at the time of their initial evaluation, Dr. Singer said. “We talk to them in the same way we talk to patients about extended-criteria candidates.”
Surgeons generally spend a lot of time explaining the nuances of what high risk actually means to patients, Dr. Freeman said. Patients should understand the possibility of getting a disease from their donor, but this risk must be put into the context of all of the others associated with transplantation, he said, adding that, almost always, the risk of disease transmission is lower. “These are not black-or-white issues,” he said.
Is High Risk a Misnomer?
The term high risk may be a misnomer when used to describe CDC high-risk organs, Dr. Freeman said. “The so-called high-risk donor population does not necessarily correlate with [a] high chance of a virus being present, at least in this study.” However, when presented with the potential of receiving an organ from a donor labeled as high risk, some potential recipients refuse the transplant, he said.
The study by Dr. Singer and colleagues identified characteristics associated with an increased risk for disease transmission, Dr. Fishman said. This is a better description than high risk, a term developed for the 1994 CDC guidelines, which targeted HIV only, he said.
Dr. Freeman hopes the CDC will consider developing a range of risk categories associated with donation of these organs and address the variables that increase the likelihood of a virus being present. The agency's latest draft guideline does not adequately address this, he noted.
“While I understand the CDC is interested in preventing unintended [viral] transmission, you can't throw the baby out with the bathwater,” he said.
Potential for Increased Use
“Until we correctly characterize these donors, this study might not make a whole lot of difference” when it comes to the wider use of CDC high-risk organs, Dr. Freeman said.
Provider fear of using such kidneys is often more common than recipient fear of transplantation with these organs, Dr. Singer said. One of the hurdles to more efficient use of these organs is changing the mind-set of transplant providers. Once this has occurred, patients can be appropriately counseled, he said.
“With continued use of these organs and careful follow-up care, we will be better able to gauge donor risk and match it to recipient need to expand the donor pool and optimize patient benefit,” Dr. Singer and colleagues wrote.
“Demonstrating that the infectious risks of these organs are low will likely lead to more CDCHR organs used, fewer CDCHR organs discarded, and an overall increase in the donor pool, which will ultimately benefit all patients on the waiting list.”