FORT LAUDERDALE, Fla.—Highly sensitized renal transplant recipients can have excellent long-term outcomes, but a greater number of genetic mismatches in these patients may lead to higher rates of acute rejection, cytomegalovirus (CMV) infections and worse graft function and survival, according to a 10-year study.

Closer immunologic monitoring may help avoid these complications and improve post-transplant outcomes, researchers said.

“It used to be that the better the HLA match, the better the kidney is,” said lead investigator Anil Paramesh, MD, Assistant Professor of Surgery at Tulane University School of Medicine in New Orleans.

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“However, many people now believe that the quality of the genetic matches is not as important as it used to be because of improvements in anti-rejection medicines. The current kidney allocation system has de-emphasized HLA matching, but this may need re-evaluation, especially for sensitized patients.”

Dr. Paramesh, who presented the study findings here at the American Society of Transplant Surgeons 10th Annual State of the Art Winter Symposium, said the effects of a greater number of HLA mismatches among highly sensitized recipients have not been very well studied.

He and his colleagues looked at long-term graft outcomes in patients transplanted at their center from 1998 to 2007 with panel reactive antibody levels greater than 80%. In one of the largest studies of its kind, the investigators looked at the outcomes in 142 kidney transplant recipients.

They divided patients into three groups (groups 1, 2, and 3) based on the number of HLA mismatches with their kidney allograft (0-2, 3-4, and 5-6 mismatches, respectively). All patients received the same immunosuppression regimens. The groups were similar with respect to time spent on a waiting list.

Groups 2 and 3 had a significantly higher incidence of acute rejection than group 1. The incidence was 4.4% in group 1, 11.4% in group 2, and 31.3% in group 3. In addition, in groups 2 and 3, the researchers observed a trend toward higher rates of CMV infection and worse graft function.

The five-year graft survival estimates were 100% in group 1 compared with 81% in group 2 and 73% in group 3. Adjusted analyses showed that acute rejection was the only significant factor associated with graft loss.

“What was significant in this study was the number of rejections,” Dr. Paramesh told Renal & Urology News. “The number of rejections was three to seven times higher in the more mismatched group than the well matched group.”

These findings suggest that highly sensitized patients may need to be managed more aggressively and immunosuppression regimens should be individualized.

Dr. Paramesh said the United Network for Organ Sharing should rethink its policy for allocating organs for these patients.

“The current allocation scheme for kidneys has taken out a lot of the priority for genetic matching because in the general population it has been shown that it doesn’t make that much difference. But they are including all patients. When you look at this specific group [of highly sensitized patients], we believe it does make a difference.”

This issue is gaining in importance, Dr. Paramesh said, because the number of highly sensitized kidney transplant recipients is increasing.