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Kidney research points to ways to more effectively use organs

WINSTON-SALEM, N.C. – Several new studies suggest how transplant surgeons can make more effective use of kidneys from deceased donors – even those that are at the outer limits of acceptance criteria – according to researchers from Wake Forest University Baptist Medical Center.

At the 13th Congress of the European Society for Organ Transplantation held in Prague, Czech Republic, Rajinder Singh, M.D., a fellow in transplantation surgery, presented the results of three studies suggesting not only the potential to expand acceptance criteria, but specific ways to achieve optimum results.

“Our experience suggests that the limits of donor acceptability may continue to expand as we are able to achieve acceptable short-term results with kidneys that once would have been discarded,” said Robert Stratta, M.D., senior researcher. “Our findings point to the importance of matching donor and recipient ages, reducing waiting times for transplantation, and taking steps to reduce delayed graft function and acute rejection.”

The research involved kidneys from deceased donors that met standard criteria for donation (SCD) as well as those from “expanded criteria” donors (ECDs). The ECD category was created by the United Network for Organ Sharing in 2002 so that higher risk donor organs, once considered unsuitable, could be transplanted safely.

The ECD category includes kidneys from deceased donors over age 60 or those over age 50 with health conditions such as high blood pressure, stroke or elevated levels of a protein called creatinine. Levels of creatinine, which is produced by muscle, are used to determine kidney function.

Extreme Donors: In one study, the researchers compared results using ECD organs with what they term “extreme” ECD organs, which included either donors over age 70; donation after cardiac death, which used to be taboo because of the risk of the organ being deprived of oxygen; organs stored more than 30 hours before transplant, or kidneys in which the filtering units were scarred at least 30 percent.

With a mean follow up of 30 months, outcomes with 80 "extreme" ECD kidneys were comparable to 71 conventional ECD kidneys. Both patient survival and survival of the transplanted organs were similar between the two groups.

Age-Matching: In a second study, the group looked at whether there is an advantage to matching the ages of donors and recipients. The study, involving 243 recipients, compared results when ECD kidneys (from donors age 60 and older) were transplanted in older recipients and SCD kidneys from younger donors (under 60) were transplanted into younger recipients to results in donor/recipient combinations in which age-matching did not occur.

Mortality was higher (9.5 percent) in the age-mismatched group than in the age-matched group (3.3 percent). The difference occurred regardless of whether the donors and recipients were older or younger than 60.

“Donor and recipient age-matching in deceased donor kidney transplants may confer a survival benefit independent of recipient age,” said Stratta, director of abdominal transplantation.

Identifying Risk Factors: In another analysis, the researchers sought to identify risk factors for kidney graft failure, which is when a transplanted organ ceases to function. They reviewed 56 cases of graft failure in 390 patients who received kidneys from deceased donors. Twenty-nine of the failed organs were from SCDs and 27 from ECDs. Risk factors for graft loss in both groups included diabetes in the recipient, recipients being over age 60, episodes of acute rejection, or delayed graft function.

Acute rejection is when the body shows early signs of rejecting the transplanted kidney. Delayed graft function is when the recipient requires temporary dialysis to support the transplanted kidney before it begins functioning on its own. Other risk factors for kidney graft failure that approached statistical significance were waiting times greater than 26 months and undergoing dialysis for more than 42 months before a transplant.

Stratta said understanding more about risk factors allows physicians to take preventive measures.

“Delayed graft function was the most important risk factor affecting ECD kidneys, and it can be markedly reduced by using a pump to force fluid through the kidneys before transplant,” said Stratta. “With SCD kidneys, acute rejection was the major risk of organ failure, which suggests the importance of sophisticated compatibility testing and strong anti-rejection medication in an attempt to improve outcomes.”