New Mayo Clinic approach to kidney transplants means more patients can be successfully transplanted

ROCHESTER, Minn. -- The Mayo Clinic kidney transplant team is using a new approach that filters out antibodies prior to surgery to overcome a major barrier to kidney transplantation in some patients. The report appears in this month's American Journal of Transplantation.

These patients have historically been ineligible for transplants because they have high levels of antibodies in their blood that suggest they would reject the organ. Yet the Mayo Clinic team has transplanted kidneys into 29 patients in this most-difficult-to-treat group of patients, with an 80 percent success rate. One to three years following the operations, 23 of the 29 patients have good, healthy functioning kidneys.

Currently 7,000–10,000 people in the U.S. are in this most-difficult-to-transplant group. They often undergo regular dialysis and wait for a compatible donor organ that their antibodies won't attack.

"Sadly, they'll languish on the waiting list," says James Gloor, M.D., a transplant nephrologist on the Mayo Clinic team. "As soon as a donor kidney becomes available, this subset of patients usually turns out to have antibodies against it, so they don't get a transplant and end up going back on the waiting list, waiting for a donated organ that they don't have antibodies against. But because they have such high antibody levels, the desired 'negative cross-match' as it's called, hardly ever happens. This can go on for 10 to 15 years. They often die on the waiting list, waiting for a negative cross-match," says Dr. Gloor.

Adds Mark Stegall, M.D., head of the transplant team: "The irony of this protocol is that some patients have been going to dialysis for 10 years -- and their donor has been driving them there all the 10 years. The presence of the antibodies in the recipient has prevented a transplant from the otherwise-acceptable living donor. Now, with just a little bit of manipulation of the patient's immune system, we've been able to perform the transplant. We basically turned the driver into the living donor."

Mayo Clinic's New Approach

The Mayo Clinic transplant team's key innovations are:

A new approach to blood tests that historically have been used to determine a good match between a patient and a donor. Instead of looking for a simple "yes-antibodies-are-present/no-antibodies-are-not-present" answer to cross-matching tests, the Mayo group considered the amount of a given antibody present in the blood. Says Dr. Gloor, "Maybe the amount of antibody against the donor may really in fact be just a tiny, tiny amount. But it's enough to turn the test to positive. In the past, we would have looked at that positive and it would work against the patient's eligibility. But now we can look at the amount of antibody, not just the presence of it. And we can see the cases when it's not much -- not real positive -- not enough to endanger the transplant."

Filtering out antibodies from the patient's blood to create a less hostile environment for the donor kidney so it can adapt. Using the idea of a wide array of antibodies that have a shallow effect -- amounts that are tiny but still sufficient to turn the cross-match test positive -- the Mayo Clinic team found that through a series of dilutions of a patient's blood, they could get a progressively weaker solution of antibodies. They could get it so weak, in fact, that the cross-match test couldn't pick it up. When they reached this point, the cross-match test would then be negative -- and a kidney transplant could safely proceed.

The Technology

To dilute a patient's antibody profile, doctors used a well-known and easily obtainable technology in a new way. They sent patients through a series of blood-filtering treatments called plasmapheresis. In it, blood is taken from the patient's body and spun in a centrifuge that sends the red blood cells to the periphery. The fluid part of the blood containing most of the antibodies is discarded, and the red blood cells are reconstituted with saline solution, then put back in the patient's body. The next day, this is done again. And again the next day for several days. Each time, the antibody strength is diluted by half. Once the patient's antibody profile is so diluted it registers as a negative cross-match, the patient follows the regular course of all transplant patients of immunosuppressive drugs.

Significance of the Mayo Work

The Mayo Clinic study may change the heart-wrenching cycling through the donor-organ waiting list. Says Dr. Gloor, "The importance of this study is that we take a group of patients, and in a doable fashion with technology that is readily available today, we can now transplant these people who otherwise would never be transplanted."

Adds Dr. Stegall, "We've decided to take on these high-risk, difficult patients and just see if we can improve their outcomes -- and the answer is 'yes.' The results have been surprisingly good. However, we believe that this is only the beginning. These types of protocols are increasing our understanding of the role of antibody in kidney transplantation. We believe that the technology will continue to improve as we know more. There are thousands of patients out there who could benefit from this or similar therapy."

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Journal

American Journal of Transplantation