By Áine Doris

The demand for kidney transplants from living donors has grown exponentially in the U.S. over the last 20 years. The reasons are positive:  Living organs are better tolerated by recipients. Survival rates are excellent at 86% over five years. And because kidney patients are covered by Medicare, taxpayers save around half a million dollars per patient over a lifetime, compared to dialysis. 

But with more patients seeking kidneys, the issue of finding compatible donors is even more pressing. Donors and recipients must be a perfect match in blood and tissue type. And that’s a problem if you are a parent, say, with type A blood looking to make a life-saving kidney donation to your type O child. As a result, there has been a increase in the number of kidney exchange registries—organizations that build databases of donors and patients and use sophisticated algorithms to match cross-compatible pairs. In other words, the type A parent gives a kidney to another needy recipient, and in return the type O child gets a matching organ.

And the principle is sound, says Vahideh Manshadi, assistant professor of operations at Yale SOM. 

“The idea is to overcome incompatibility issues between a donor and recipient pair. Let’s say you have a mother donor and her child who needs a kidney but doesn’t have the same blood or tissue type. The mother-child pair can enter a kidney exchange registry. The exchange registry draws on its database to find multiple potential connections—matches—not just for the child but for the mother too.”

The connections in the registry can be complex, with a series of donations creating a cyclic exchange between the mother and the donor who ultimately provides the kidney that is compatible with her child. 

Exchanges can also be initiated by altruistic individual donors who offer a kidney to anyone in need, Manshadi says. “Such a donation creates a kind of domino effect that frees one donor to be matched with a range of potential recipients at a later time. Exchange registries work by creating multiple cyclic exchanges or pathways—chains—to maximize the number of potential exchanges.”

Growing demand from patients and market competition between these exchange registries have led to an increase in the frequency of their match runs—a hike in the number of searches for matching donors and recipients—that could be undermining the very benefits they claim to offer. 

“The issue is time,” Manshadi explains. “If centers are matching people too frequently, it could be that they’re depleting their databases too fast. In theory, these databases need time to grow in order to function better—you need more people coming in with different blood types to maximize the total number of potential matches. So we were interested in seeing if high-frequency match runs might actually be hurting the total number of transplants a center was able to offer. And if there might also be a tradeoff in terms of longer wait times for patients.”

To test the effects of more frequent match runs, Manshadi and colleagues from Stanford, the University of Toledo, and MIT conducted a number of detailed simulations using clinical data from two prominent kidney exchange registries in the United States: the Alliance for Paired Donation and Methodist San Antonio, which run multi-hospital and single-center exchanges respectively.


Read the study: “Effect of match-run frequencies on the number of transplants and waiting times in kidney exchange”

The researchers simulated different scenarios facing the two registries across a range of variables, feeding the simulation from the registries’ historical pools both of patient-donor pairs and non-directed donors—altruistic individual donors who offer a kidney to anyone in need. They then examined the rates at which people were entering the programs and leaving them following successful (simulated) transplantation. 

The results were surprising, says Manshadi. “We didn’t find any evidence that higher-frequency match runs were reducing the overall number of transplants by depleting the pool of potential donors. The total number of transplants remained stable.” 

What the researchers did find, however, was an unexpectedly high number of patients in both programs whose antibodies made them hard to match—what are called sensitized patients. 

“The majority of patients in these programs are sensitized,” Manshadi says. “These patients have such high levels of antibodies in their blood that they are more likely to reject a donor organ. Frequent or infrequent matching will have little effect on them because it’s so much harder to find a donor whose kidney they can accept.”

The best way of improving the outlook for these patients, says Manshadi, is to ensure they are prioritized when searching for matches. That, and find new ways of increasing—and diversifying—the number and range of donors coming into exchange programs. 

“By working constructively towards greater collaboration, these centers would see considerably greater traction in the number of lives they are able to save each year.”

“Let’s say you have 50 new donor-recipient pairs joining your program every month. If you increase that number to 100, you significantly increase the fraction of potential matches both for easy- and hard-to-match patients. The challenge to exchange programs is finding a way to make this happen.” 

The researchers found another significant benefit in increasing match frequency: it reduces patients’ wait time without hurting their chance of finding donors. “Influenced by our research, many programs have increased their match frequency.” Manshadi says. 

One avenue that the researchers recommend is increased collaboration between centers. With more than half a million Americans suffering from kidney failure, and the waiting list for a transplant expected to grow by 36,000 this year, that’s a key takeaway for policymakers.

“The kidney exchange market in the U.S. is characterized by competition, and that’s not necessarily a bad thing,” Manshadi says. “But our research indicates that by working constructively towards greater collaboration, by combining their efforts to create a unified database, these centers would see considerably greater traction in the number of successful matches and transplants they are able to perform and lives they are able to save each year.”