It enables more precise assessment of kidney recipient antibodies

Renal transplant specialists have developed an innovative new laboratory technique to improve opportunities and success rates for kidney transplant candidates who are at high risk for organ rejection due to previous exposure to donor antigens.

The technique, described in Transplantation (2008;86:820-824), enables more precise determination of the specificity and strength of a transplant candidate’s antibodies.

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“It is important for physicians to know about this because about 30% of the patients on the waiting list have a problem with antibodies to HLA antigens and can’t have a transplant,” said researcher Stanley C. Jordan, MD, medical director of the Kidney Transplant Program at Cedars-Sinai Medical Center in Los Angeles.

Previous studies have shown that tissue compatibility issues exist for all patients receiving transplanted organs, but risk are  much greater in those with high exposure to “non-self” HLAs. High exposure may be related to blood transfusions, previous transplantation, or even pregnancy. The immune system is then sensitized to those HLA antigens.

Dr. Jordan and his colleagues began studying the use of IV immunoglobulin (IVIG) 20 years ago as a way to modulate the immune system and “desensitize” highly sensitized patients. IVIG therapy became a Medicare-approved therapy in 2004 when it was found effective in a multicenter study. Now, Dr. Jordan and his collaborators have developed laboratory protocols using antigens and patient blood that are useful in predicting which patients are most likely to benefit from desensitization. Known as solid-phase assays, the new technology uses beads coated with specific HLA antigens to determine the strength of a patient’s antibodies more precisely.

“With solid-phase assays, we can tell the physician that a patient has antibodies to a particular antigen because it bound to a specific bead,” said study investigator Nancy L. Reinsmoen, PhD, director of Cedars-Sinai’s HLA Laboratory. “This allows us to do a more quantitative analysis and predict more accurately which patients are the best candidates to have a successful transplant with a low risk of acute rejection. We can also predict which patients are at very high risk for acute rejection. The physicians can then pre-emptively treat patients before they go through a full-blown acute rejection episode, which is a risk factor for chronic rejection.”

The aim of the current study was to determine the level of donor-specific antibody (DSA) that allows for successful transplantation after desensitization with IVIG and rituximab and to identify patients at risk for antibody-mediated rejection. Dr. Jordan said this combination therapy is less costly and appears to offer superior benefits to IVIG alone, improving transplant rates to 80% of treated patients.

In the current study, antibody levels were tested before treatment, before transplantation, and several times after transplantation in 16 sensitized patients. Eight patients received organs from deceased donors and eight received organs from living donors.

“Sixty-three percent of the patients in this study were transplanted despite having a positive crossmatch,” Dr. Reinsmoen explained, noting that because the patients had been desensitized, the crossmatch was at a low enough level to greatly reduce the chance of an acute rejection episode.

“You can transplant [kidneys] with any type of HLA antibodies, which is something that could not be done in the past,” Dr. Jordan told Renal & Urology News. “So clinicians can adopt these protocols. The tests allow for an extra measure of confidence in predicting when patients are ready for transplant.”