For patients with end-stage renal disease (ESRD), kidney transplantation offers a more durable and successful treatment option than dialysis. The transplant recipient, however, is at increased risk of infection because of the concurrent use of potent immunosuppression to prevent rejection of the allograft.
In the past, infections were one of the most common causes of death in this patient population. With improvement in diagnostic methods and treatment, as well as heightened awareness of the complications of over-immunosuppression, there has been a steady decline in the incidence of fatal infections.
However, donor-derived infections— those that are transmitted from organ donor to transplant recipient—have been the focus of increased attention since a November 2007 report documenting the transmission of HIV and hepatitis C from an initially antibody-negative donor to four transplant recipients. The transmission of rabies, West Nile virus, and lymphocytic choriomeningitis virus have also been reported in recent years.
Oftentimes, these infections can be anticipated through pretransplant evaluation of donor serology. Due to the limitations of current screening practices, though, transmission of serious infections that confer significant morbidity and mortality do occur.
Screening Inadequate in Certain Cases
Donor-derived infections may be viral, bacterial, fungal, or parasitic. Screening of potential donors is an essential component of the transplant process. Specific guidelines for such screening have been established by the American Society of Transplantation and other organizations.
A detailed social and medical history of the potential donor is one requirement. However, the history may not be entirely accurate, as it is obtained from relatives of the deceased donor, who may not be completely familiar with the medical and social information. The time interval between the death of the donor and organ procurement is limited, and complete and accurate information may not be available prior to transplantation.
Serological testing is also required. Frequently used screening tests for potential donors are listed in Table 1.
However, the fact that clusters of donor-derived infections occur despite these guidelines suggests that screening methods are inadequate in certain instances and need improvement.
All active infections in the donor should be treated prior to transplantation. It may not always be possible to have complete resolution of the infection, and the decision to use organs from such donors should be based on the urgency of transplantation for the recipient, the severity of end-stage renal disease, and whether another organ offer is forthcoming.
Bacterial infections are treated with appropriate antibiotics, with the duration of therapy depending on the virulence of the organism. Syphilis is not considered a contraindication to transplantation, but it requires treatment of the recipient with an appropriate course of penicillin. Active systemic fungal infections, on the other hand, are a contraindication to transplantation.
Viral infections may be difficult to diagnose given the limitations of current serological methods. Active HIV infection excludes individuals from being organ donors. Hepatitis C- and hepatitis B-positive donors are ruled out expect in special circumstances.
The shortage of deceased donors, coupled with increased wait times and mortality on the transplant waiting list, has resulted in more frequent utilization of expanded-criteria-donor kidneys and the consideration of marginal or high-risk donors.
In 1994, the Centers for Disease Control and Prevention (CDC) established criteria for the designation of donors as high risk (see Table 2). Approximately 8.6% of deceased donors fall into this category. The use of kidneys from these donors remains controversial because of the high-profile cases involving HIV and hepatitis transmission.
Some organ procurement organizations have started to use nucleic acid testing (NAT) in an effort to shorten the window period—the time between infection and detection of the antigen in the serum—and more precisely identify HIV and hepatitis infections.
Window periods for the commonly used enzyme-linked immunosorbent assay (ELISA) are 22 days for HIV, 66 days for hepatitis C, and 44 days for hepatitis B. NAT can reduce this window period to nine days for HIV, seven days for hepatitis C, and 22 days for hepatitis B. The disadvantages of NAT testing, though, include higher cost and more time. False positives are possible, leading to a higher organ discard rate.
For example, a study by Duan and colleagues looking at how CDC-defined high-risk status affected donor utilization demonstrated that 41 otherwise standard kidneys were wasted per year if they had a CDC high-risk label.
A survey of transplant infectious disease physicians by Ison and Stosor showed significant variability in the acceptance and management of organs from high-risk donors in the United States. The authors were of the opinion that the Public Health Service guidelines need to be revised to more accurately reflect the use and impact of newer testing methods and that a central database needs to be created so that current policies and future guidelines can be better understood.
Recent efforts to review current practices and address donor-derived infections have resulted in the formation of the United Network for Organ Sharing (UNOS) Disease Transmission Advisory Group (DTAG). UNOS also requires that special informed consent be obtained before organs classified as high risk by the CDC are transplanted.
More Rigorous and Uniform Screening
Newer testing methods and advances in technology have improved organ screening methods and reduced the incidence of donor-derived infections. However, such infections still occur with sufficient frequency to suggest that more rigorous and uniform screening is required. Policies should be updated, and molecular diagnostic methods that are cost-effective and can be rapidly performed before transplantation need to be developed.
1. Grossi PA, Fishman JA; AST Infectious Disease Community of Practice. Donor-derived infections in solid-organ transplant recipients. Am J Transplantation 2009;9(suppl 4):S19-S26.
2. Fischer SA, Avery RK; AST Infectious Disease Community of Practice. Screening of donor and recipient prior to solid--organ transplantation. Am J Transplantation 2009;9(suppl 4):S7-S18.
3. Duan KI, Englesbe MJ, Volk ML. Centers for Disease Control ‘high-risk’ donors and kidney utilization. Am J Transplantation 2010;10:416-420.
4. Reese PP, Feldman HI, Asch DA, et al. Transplantation of kidneys from donors at increased risk for blood-borne viral infections: recipient outcomes and patterns of organ use. Am J Transplantation 2009;9:2338-2345.
5. Ison MG, Stosor V. Transplantation of high-risk donor organs: a survey of US solid-organ transplant center practices as reported by transplant infectious diseases physicians. Clin Transplantation 2009;23:866-873.
6. Kucirka LM, Alexander C, Namuyinga R, Hanrahan C, Montgomery RA, Segev DL. Viral nucleic acid testing (NAT) and OPO-level disposition of high-risk donor organs. Am J Transplantation 2009;9:620-628.