What determines compatibility between a donor and a recipient?

 

Three major factors determine whether a donor and a recipient are compatible: blood type, tissue type, and cross-matching:

  

Blood Type:  A donor and recipient must have either the same or compatible blood types. There are 4 basic blood types: A, B, AB, and O. Type O, the “universal donor,” is compatible with all other types for donation but can receive only Type O blood. Types A and B are compatible with two others, and Type AB can accept only Type AB.

© Johns Hopkins University

 

Although a donor and recipient must have either the same or compatible blood types, fortunately, donors with incompatible blood types can, if they wish, participate in a kidney exchange program. There are two types of kidney exhanges: paired donation and chain donation.

Paired Donation:  In paired donation, 2 sets of incompatible donor/recipient couples cross-exchange kidneys so that each recipient receives a compatible kidney. In other words, the two pairs "swap" kidneys, as illustrated below.

 

Chain Donation:  Sometimes, multiple pairs of donors exchange kidneys in a chain donation. While most domino donations involve only a few pairs, in 2011, the world's longest chain to that date consisted of 60 people: 30 donors and 30 recipients. Thirty lives were saved all because one man wanted to donate a kidney.

 

You can read an excellent news article about domino donation here.

Tissue Type:  This refers to the compatibility of donor and recipient tissue cells. Every person inherits a unique set of certain proteins called antigens. Antigens stimulate the immune system to attack and fight off (or reject) foreign substances that are harmful to the body.  Six of these antigens (3 inherited from each parent) are relevant to kidney transplantation. The more antigens the donor and recipient have in common, the more compatible the match. Thus, a match between 6 out of 6 antigens (6:6) is more compatible than a 5:6 match, a 4:6 match, and so on. The more compatible the match, the lower the chance of rejection, resulting in a longer-lived kidney. A 6-antigen (or “perfect”) match is the single best match that can occur between a donor and recipient. Siblings who have the same mother and father share this ideal match 25% of the time. Six-anitgen matches can occur among the general population, but it is rare.  Regardless of the match, a kidney recipient must take anti-rejection drugs for the rest of his or her life to prevent the immune system from rejecting the foreign kidney.

 

Tissue type has become the least important of the 3 compatibility factors, thanks to stronger anti-rejection drugs that have been developed during the past decade. Stronger drugs can overcome the effects of poor antigen matches such that even 0:6 "matches" do not prevent transplantation. However, anti-rejection drugs make the recipient more susceptible to serious complications, including diabetes, cancer, and fatal infections. The dose of anti-rejection drugs necessary to prevent rejection is directly related to the closeness of the antigen match: the closer the match, the lower the dose. So even though tissue type has become less important than in the past, a close match still has advantages over a poor match. Far more important than the antigen match, however, is the source of the kidney: The most poorly matched live-donor kidney (0:6) has a far better chance of successful transplant than the best-matched (6:6) deceased-donor kidney.  

 

Cross-matching:  Cross-matching is the most important compatibility test. It determines whether the recipient has developed antibodies (proteins that help the body fight infection) that will react against the donor’s kidney. Such antibodies usually develop in response to pregnancy, blood transfusions, or previous transplants. Cross-matching involves 10–15 tests in which the donor’s blood cells are mixed with the recipient’s blood cells. If the recipient’s antibodies react against the donor’s cells, it indicates that the kidney would be rejected immediately and therefore cannot be transplanted. This is known as a positive match, or a “no go.” If no reaction occurs, it is a negative cross-match, or a “go,” and the transplant can be performed. (The language seems a little backward. In this case, “positive” means “present,” and “negative” means “not present.”) The consequence of a positive cross-match is that a recipient must wait much longer for a suitable kidney.

 

"Dave is healthy again, really--you should see the guy, it's a real miracle," Winer wrote in a later blog. "We go out to eat, go to baseball games, take long walks, and kid each other about stuff that doesn't matter, and cheer each other on as we go forward. Dave has three sons and is raising his nephew, each of whom has a 50% chance of having inherited the disease.

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Dave Jacobs’ younger brother, Brandt, had already died of an inherited kidney disease when his own 25-year career was cut short by the same illness. The disease forced Jacobs, a highly successful technology veteran with Macromedia, Inc., to resign his vice-presidency.

Good friend Dave Winer, who pioneered the development of weblogs, RSS, podcasting, and web-content management software, appealed in his  blog for a donor: “I love this guy," he wrote. "Unfortunately, dialysis has not been easy and is wrecking his health. He's a shadow of his former robust self. My friend is dying, and I hope someone can help him.” 

Jacobs spent 3 years on dialysis. "The first day I sat on dialysis, I sat next to a guy my age, my disease. I was scared; he told me, 'Hey, no problem, it's just boring.' Fifteen minutes later, he coded out and died."    

After a 5-year wait during which he nearly died, Jacobs received a kidney. His sister, Cher, who had also inherited the disease, had a transplant the same year. During the time that Dave had been waiting, he identified areas in the medical field that he thought could be improved through technology. (Looks worlds better following his transplant, doesn't he?)

Jacobs founded Silverstone Solutions, Inc., and developed Matchmaker,a software program designed to make better use of available living-donor kidneys by identifying matching pairs among large groups of people. Silverstone is now the leading provider of such software.1

1 Methuselah Foundation

Using complex matching algorithms, Matchmaker connects kidney-donor pairs, finding the optimal match to improve transplant outcomes. Watch as Jacobs--back to his robust self--demonstrates his product.