When Survival Benefit Transcends Infection Risk

The 22-year-old single mom flags me down at the dialysis unit. “The transplant team discussed getting my consent for increased risk kidney donors – do you think this is something I should go for?” Disclaimer: I’m not a transplant nephrologist. Worrisome thoughts hit my mind… She is so young. Why take on any risk of contracting HIV or hepatitis C? Patients so young will need at least 2-3 transplants through their lifetime. Will she really get a good quality kidney that will hopefully function for 15-20 years, if it was from an increased risk for disease transmission (IRD) donor? (The “increased risk” refers to behaviors that increase risk of contracting HIV, hepatitis B or hepatitis C.)

Fortunately, transplant outcomes data has been reassuring and shows that organs from IRD donors are non-inferior to non-IRD organs. In fact, a recent report from the American Journal of Transplantation showed a survival benefit in accepting IRD kidneys. In patients who declined an IRD kidney, only 31% later received a kidney transplant (5 year follow up period) and this was of a lower quality than the initial IRD organ offered.
Organ transplantation from a deceased donor is the ultimate paradox of a new lease on life from someone other’s tragedy. But the reality is that most patients waiting for a transplant will die before an organ becomes available. There are ~115,000 people on the UNOS (United Network for Organ Sharing) wait list and the majority are waiting for a kidney transplant (~95,000); average wait-time for a kidney from a deceased donor is 5 years. The longer a wait-listed dialysis patient is living with kidney failure and is exposed to the uremic constellation of metabolic derangements, inflammation, anemia and blood pressure fluctuations – the higher the risk of progressive vascular injury and sudden cardiac death. End stage kidney failure is a huge public health burden, totaling $34 billion per year in Medicare spending.

Thus from the perspective of both the individual patient and tax dollars, optimizing the number and quality of transplants is a big deal. Which brings us back to the topic of IRD donors who have a history of behaviors that put them at risk of having HIV, hepatitis B or hepatitis C. Many of these donors are otherwise young and relatively healthy; this means that there is the potential to transplant high quality organs from 1 donor to as many as 8 recipients. In the U.S. we are seeing an alarmingly fast-growing segment of IRD organ donors in the opioid overdose crisis. In 2016 there were ~42,000 deaths from opioid overdose, a five-fold increase from 1999.

A recent NEJM correspondence states “the drug-abuse epidemic has been associated with a sharp increase in the recovery of organs from brain-dead donors in the United States but not in Europe”. In the U.S., the proportion of organ donors who died from drug intoxication increased from 1.2% of all donors in the year 2000 to 13.7% as of 2016. In contrast, the Eurotransplant registry from 8 European countries showed no significant change (≤1% per year). The outcomes data from this donor population is the silver lining in this tragic crisis. In an Annals of Internal Medicine analysis of almost 20,000 organs transplanted from over 7,000 drug-overdose donors, 5-year patient and graft survival was similar as compared to organs from trauma- or medical-death donors.

The majority of IRD donors who have no prior history of HIV or hepatitis won’t have a transmissible virus. But right now we don’t have tests that allow us to be 100% certain about a donor’s infectious status at time of organ procurement. The concept of “increased risk” refers to the risk of recent acquisition of HIV or viral hepatitis that is missed in the Nucleic Acid Testing (NAT) window period. (Window period = the time between potential infection and the point when the test will give an accurate result, thus you get false-negative results.) Don’t get me wrong, NAT is a remarkable improvement over prior serologic testing; for example, hepatitis C NAT has a window period of 3-5 days as compared to 70 days with traditional antibody (serologic) testing. NAT itself is a controversial topic since false-positive results can occur, and experts have raised concerns that this may result in unwarranted discard of organs. However in IRD donors NAT is a powerful tool for more accurate risk assessment. For example, donors with recent IV drug use with negative serological testing have a risk of undetected hepatitis C of 300.6 per 10,000 donors (3%). Having both negative serology and negative NAT reduces this risk to 32.4 out of 10,000 donors (0.3%).

To summarize: the U.S. is facing an epidemic of drug-overdose deaths. Simultaneously, there is a long list of patients waiting for a life-saving heart, kidney, lung or liver transplant. These two issues have become intertwined. It is an unsettling topic of discussion, but it behooves us to counsel patients that organ transplants from “increased risk” donors are non-inferior and improve survival.

Wei Ling Lau Headshot

Wei Ling Lau, MD is Assistant Professor in Nephrology at University of California-Irvine. She is currently funded by an AHA Innovative Research Grant, and has been a speaker for CardioRenal University and the American Society of Nephrology. Follow her on Twitter @Kidneys1st

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