Survival Benefit with Transplants from Incompatible Live Donors

A recent multicenter study validated single-center evidence that patients who received kidney transplants from HLA-incompatible love donors had a substantial survival benefit compared with patients who did not undergo transplantation and those who waited for a kidney from a deceased donor. Babak J. Orandi, MD, R.A. Montgomery, MD, Dorry L. Segev, MD, and colleagues reported results of the 22-center study in the New England Journal of Medicine [2-16;374(10):940-950].

There are more than 32,000 patients waiting for kidneys in the United States who have anti-HLA antibodies (sensitized patients), making it difficult to find a match with a compatible donor. Patients in that population may stay on the transplant waiting list for years without finding a suitable donor.

Because centers that perform transplantations from incompatible living donors may be subjected to regulatory scrutiny and loss of certification from the Centers for Medicare & Medicaid Services, many centers have avoided performing such transplantations. However, for most sensitized patients, it is not possible to receive a compatible kidney; they must either undergo desensitization or stay on the waiting list. Remaining on the waiting list without receiving a kidney is associated with a high mortality rate.

Three of the authors of the current study previously reported a survival benefit at Johns Hopkins University of undergoing desensitization and transplantation with a kidney from an incompatible live donor. It was unclear, however, how generalizable the results were. To quantify the effect of transplantation with kidneys from incompatible live donors on survival among patients at centers across the United States, the researchers compared recipients of such transplants in a multicenter cohort with matched controls who remained on the waiting list for a kidney transplant (waiting-list-only control group) or received a transplant from a deceased donor (waiting-list-or-transplant control group).

The study included 1025 patients at 22 centers who received kidney transplants from incompatible live donors: 185 with a positive Luminex assay but a negative flow-cytometric cross-match, 536 with a positive flow-cytometric cross-match but a negative cytotoxic cross-match, and 304 with a positive cytotoxic cross-match. Among recipients with a positive Luminex cross-match, mean age was 45.4 years; among those with a positive flow-cytometric cross-match, mean age was 45.5 years; and among those with a positive cytotoxic cross-match, mean age was 43.8 years.

In the three subgroups, respectively, the majority of patients were women (67.6%, n=125; 68.1%, n=365; and 64.8%, n=197). Overall, 413 (40.3%) had received a previous kidney transplant (32.4% (n=60), 38.1% (n=204), and 49.0% (n=149), respectively in the subgroups). Of the total cohort of recipients, 16.4% (n=168) were black (17.3% [n=32]; 18.7% [n=100]; and 11.8% [n=36], in the subgroups, respectively).

Median percentage of panel-reactive antibody was 51.0% among recipients with a positive Luminex assay, 57.5% among those with a positive flow-cytometric cross-match, and 85.0% among those with a positive cytotoxic cross-match. The mean duration of renal replacement therapy (RRT) was 5.6, 6.9, and 9.0 years, respectively.

Of the overall group of patients who received a kidney transplant from an incompatible live donor, mean age was 45.0 years, compared with 45.9 years in the waiting-list-or-transplant control group (P=.07) and 46.4 years in the waiting-list-only control group. The difference in mean age between recipients of transplants from incompatible donors and the waiting-list-only group was significant(P=.001), but clinically negligible.

Compared to the waiting-list-or-transplant group and the waiting-list-only group, recipients of transplants from incompatible living donors had a history of slightly more kidney transplants (P=.004 and P=.02, respectively). There were no differences between groups in sex, black race, percentage of panel-reactive antibody, diabetes status, or mean number of years on RRT.

In the waiting-list-or-transplant group, 45.4% (n=2326) of the controls ultimately received a kidney transplant from a deceased donor. Mean follow-up for those patients was 7.3 years from the time of matching and 5.0 years from the time of transplantation. Follow-up for the patients in the waiting-list-or-transplant control group who did not receive a transplant was 4.8 years from the time of matching.

The patients who received kidney transplants from incompatible live donors had a significant survival benefit compared with the two control groups (P<.001 for both comparisons). The improved survival rate was seen at 1 year (95.0% vs 94.0% for the waiting-list-or-transplant control group and 89.6% for the waiting-list only control group); 3 years (91.7% vs 83.6% and 72.7%, respectively); 5 years (80.6% vs 74.4% and 59.2%); and 8 years (76.5% vs 62.9% and 43.9%).

Compared with remaining on the waiting list or receiving a transplant from a deceased donor, receiving a kidney from an incompatible live donor was associated with an absolute increase of 13.6 percentage points in the survival rate at 8 years, and an absolute increase of 32.6 percentage points compared with remaining on the waiting list and not receiving a transplant from a deceased donor. Receipt of a kidney transplant from an incompatible live donor was associated with a survival benefit at all donor-specific antibody levels.

Study limitations included the heterogeneity in antibody testing and in the interpretation of test results among the centers; the change in the measure of sensitization in 2009, when the calculated panel-reactive antibody supplanted the traditional panel reactive antibody system; and variation across centers in desensitization protocols and success rates, induction and maintenance immunosuppressive regimens, and treatment of antibody-mediated rejection.

In summary, the authors said, “This multicenter study validated single-center evidence that patients who received kidney transplants from HLA-incompatible live donors had a substantial survival benefit as compared with patients who did not undergo transplantation and those who waited for transplants from decreased donors.”

Takeaway Points

  1. Researchers conducted a 22-center study to validate results from a single-center study demonstrating improved survival among patients receiving from an HLA-incompatible love donor compared with remaining on the waiting list.
  2. Recipients of kidneys from the incompatible live donors had higher survival rate compared with controls on the waiting-list-only control group and controls in the waiting-list-or-transplant control group at 1 year, 3 years, 5 years, and 8 years.
  3. The survival benefit was significant at 8 years across all levels of donor-specific antibody.