Despite immunologic challenges, transplanting across human leukocyte antigen (HLA) antibodies may be a significantly better long-term survival option than waiting years for a compatible donor, according to a new Johns Hopkins University School of Medicine study of more than 1,000 incompatible kidney transplants.

Results of the analysis, published in the March 10 issue of The New England Journal of Medicine, concluded that patients with “donor-specific” immune system antibodies against a living donor experience a survival rate of 76.5% if they undergo an incompatible living donor transplant, versus 43.9% if they remain on dialysis waiting for a compatible organ to become available or 62.9%  if such a compatible organ does become available.

There are roughly 20,000 patients at any one time on a donor waiting list who are “highly sensitized and for whom finding a compatible donor is nearly impossible,” says lead author Dorry Segev, MD, PhD, associate professor of surgery at the Johns Hopkins University School of Medicine. “That’s a lot of people who could have a better chance at surviving if they are allowed to move forward with incompatible live donor transplantation.”

“For the first time, we have definitively shown that incompatible live donor kidney transplantation provides almost twice the survival of a patient’s next best option. This is great news for patients who have healthy, willing live donors but who have been relegated to the waiting list because of HLA incompatibilities. Through this study, we now know that those donors can donate today, those transplants can happen and those lives can be saved.”

Incompatible live donor kidney transplantation, says Segev, was championed at The Johns Hopkins Hospital 15 years ago and later adopted by many other transplant centers around the country. This is the first study to evaluate whether this treatment option was working nationally and was beneficial to patients. To study this, Segev and his team looked at the survival rates of 1,025 adult incompatible live donor kidney transplant recipients in 22 centers across the U.S.

The outcomes for the incompatible recipients were then compared to study controls — or patients who looked like the incompatible recipients but remained instead on the waiting list on the day that the incompatible transplant occurred — matched on a variety of factors, including age, sex, ethnicity, blood type and other diseases, such as diabetes. They studied two sets of controls: those who remained on the waiting list but never received a transplant (waitlist-only), matched from a pool of 200,769 patients, and those who remained on the waiting list and eventually received a transplant (waitlist-or-transplant), matched from a pool of 349,844 patients.

They found that survival rates were consistently higher for incompatible live donor kidney transplant recipients at one year — 95% versus 94% waitlist-or-transplant and 89.6 % waitlist-only — three years — 91.7 percent versus 83.6 percent and 72.7%— five years — 86% versus 74.4% and 59.2% — and eight years — 76.5% versus 62.9% and 43.9%— in comparison with the control groups.

Data were analyzed with and without information from transplant patients treated at the highest-volume center in the study, The Johns Hopkins Hospital, to address the possibility that outcomes would not be better at high-volume centers that have more experience with kidney transplantation.  Segev says survival rates were equivalent in high- and low-volume centers, as were survival rates of control groups.

He noted that “significant survival benefit” was seen across all levels of incompatibility, ranging from antibody only detected by the most sensitive testing to antibody that is strong enough to cause a positive flow or cytotoxic cross-match. The eight-year survival rate for those with positive HLA specific antibody detection tests but a negative flow cross-match survival rate was 89.2%, compared to 65% and 47% for control groups; 76.3%, compared to 63.3% and 43% for those with positive flow but negative cytotoxic cross-matches; and positive cytotoxic cross-matches — 71.0% versus 61.5% and 43.7% for those with positive cytotoxic cross-matches.

Segev and donor waitlist organizations say there are more than 32,000 patients awaiting kidney transplantation in the United States who have developed antibodies against HLAs, key components of the immune system. These antibodies make it very difficult to match such “sensitized” patients with a compatible donor, many of whom remain on waitlists for years without a suitable donor ever materializing.

Desensitivity, or HLA treatment, can be expensive. However, Segev notes, dialysis is more expensive.

“Incompatible transplantation is essentially one-tenth of the price of dialysis for a patient stuck on the waitlist,” explains Segev. “This study underscores the importance of innovative treatment options, such as incompatible live donor transplantation.”

The investigators caution that managing immune system incompatibilities in this set of patients is complicated, carrying higher risks of serious side effects and organ failure than compatible transplants.

Segev emphasizes that for most sensitized patients, however, receiving a compatible live donor kidney is rarely an option, and their only choices are to undergo incompatible transplantation or remain on the waiting list, an option associated with a very high mortality rate.

“In other words,” Segev says, “it may be in the best interest of the patient to receive a transplant from an incompatible donor, even though the success rate is lower for such transplants than for those from compatible donors.

“It’s always quicker and better to find family members, co-workers or friends to donate their kidneys, rather than wait on the transplant waiting list for a deceased donor organ,” says Segev. “But all too often, the family member or friend is HLA-incompatible and, during the wait for a compatible organ, the patient gets sicker and sicker. This can become costly — physically, emotionally and financially — for the patient and his or her loved ones.”

Other authors on the paper are Babak J. Orandi, Xun Luo, Allan B. Massie, Bonne E. Lonze, Rizwan Ahmed, Kyle J. Van Arendonk, all of the Johns Hopkins University School of Medicine.