Increased graft survival of HLA-matched kidney transplants supports national sharing, study finds.

A superior graft outcome with little increase in the duration of cold ischemia justifies national sharing of HLA-matched kidney transplants, according to the results of a study published in the October 12th issue of the New England Journal of Medicine.

Steven Takemoto, MD and colleagues from the University of California at Los Angeles (UCLA) compared the rates of rejection and actuarial graft survival for 7,614 HLA-matched and 81,364 HLA-mismatched cadaveric kidney transplants reported to UNOS between October 1987, when a program for national sharing of HLA-matched kidneys was launched, and September 1999. To assess the effects of the extended period of ischemia associated with shipping HLA-matched kidneys, the investigators identified 3,562 pairs of cadaveric kidneys in which one kidney went to an HLA-matched recipient and the other was transplanted into an HLA-mismatched recipient.

"The estimated 10-year rate of graft survival was 52% for HLA-matched transplants, as compared with 37% for HLA-mismatched transplants," wrote Takemoto and coauthors. "The estimated half-lives of the transplants were 12.5 years and 8.6 years, respectively."

After adjusting for the effects of demographic characteristics, at 10 years, the overall rates of graft survival and the rates of functional-graft survival (with data censored on patients who died with a functioning graft) were 10% and 11% higher, respectively, for HLA-matched transplants than for HLA-mismatched transplants, the researchers reported. Among 3,562 pairs of kidneys, HLA-matched transplants had higher rates of survival, a lower incidence of episodes of rejection, and a reduced risk of loss due to rejection.

"Before the kidney-sharing program was initiated, only 2% of transplants were HLA-matched," the investigators wrote. "After the program was initiated, 5% of kidneys were transplanted in HLA-matched recipients with use of the 6-antigen matching criteria. Use of the phenotypic criteria increased the percentage to 7%, and use of the no-mismatch criteria increased it to 13%. The survival rate of HLA-matched kidney transplants was similar regardless of the criteria by which they were selected." The percentage of HLA-matched transplants could be further increased, according to the authors, by extending the organ-sharing network to include Canada, as many Canadian cities are close to those in the US.

Since UNOS established the national kidney-sharing program in 1987, many have argued that the resultant increased duration of cold ischemia would offset the benefit of shipping kidneys to HLA-matched patients. Indeed, in their analysis of nearly 64,000 cadaveric renal transplants reported to UNOS between 1990 and 1998, researchers at the University of California at San Francisco (UCSF) recently reported that recipients of kidneys with zero mismatches but with cold ischemic time greater than 36 hours had no survival advantage over patients with mismatched kidneys kept cold for less than 24 hours (Transplant News, September 24, 2000).

In the UCLA study, more than 83% of the HLA-matched kidneys were shipped to distant transplant centers, whereas 77% of the HLA-mismatched kidneys were shipped within the local service area of the organ procurement organization. Nonetheless, the mean duration of cold ischemia was comparable-23 hours for patients given HLA-matched kidneys and 22 hours for patients who received HLA-mismatched kidneys-and well within the cut-off point set by the UCSF investigators.

During the study period, the researchers noted that the proportion of kidneys from older cadaveric donors steadily increased in response to the growing demand for transplants. In 1988, 6% of transplanted cadaveric kidneys were from donors over age 55 years; that fraction increased to 13% by 1997. Donor age had a significant effect on 10-year graft survival among recipients of HLA-matched kidneys: 68% in patients whose donor was age 15 years or younger, 32% in those whose donor was older than 55 years. Because an estimated 70% of kidneys from donors older than 60 years of age will be lost within 10 years of transplantation, the authors recommended that "young recipients should not undergo transplantation with organs from older donors, even if they are HLA-matched."

In addition, and for reasons that are unclear, HLA-matching resulted in no significant improvement in long-term graft survival among black recipients. As blacks reportedly have an increased rate of graft loss when blood pressure is uncontrolled after transplantation, Takemoto et al recommended lowering blood pressure in hypertensive black recipients prior to transplantation as one strategy for improving outcome.