ABO-Incompatible Living Donor Kidney Transplantation and Patient Survival

As one method of accommodating the increasing shortage of organs available for transplant, blood group ABO-incompatible (ABOi) living donor kidney transplantations have been increasing. However, ABOi transplant recipients are at approximately 2-fold higher risk of antibody-mediated rejection than ABO-compatible (ABOc) transplant recipients.

Among ABOi transplant recipients, the risks of developing other post-operative complications are also higher than among ABOc transplant recipients, including a 2.1-fold higher risk of pneumonia, a 3.5-fold higher risk of a wound infection, a 1.5-fold increase in urinary tract infection/pyelonephritis, and a 1.8-fold higher risk of postoperative hemorrhage. ABO incompatibility also adds $32,000 to the cost of living donor kidney transplantation over the costs of blood group-compatible transplantation.

Data regarding differences in graft survival between the two groups are inconsistent, according to Allan B. Massie, PhD, MHS, and colleagues. Some previous single-center studies have reported comparable graft survival between ABOi and ABOc kidney transplant recipients. ABOi experiences in the United States, Europe, Japan, and Korea have also demonstrated the feasibility of obtaining equivalent graft-survival outcomes. However, a retrospective study of US patients in the Scientific Registry of Transplant Recipients (SRTR) reported higher risk for graft loss within the 2 weeks following transplant in recipients in the ABOi patient population. The 2-week post-operative period is associated with a 2.3-fold higher risk for graft loss in the ABOi group.

Transplantation programs are graded by the SRTR and the Centers for Medicare & Medicaid Services for 1-year patient and graft survival; however, performance grading does not adjust for ABO incompatibility. Dr. Massie and colleagues recently conducted a retrospective cohort study designed to assess the difference in patient survival between ABOi living donor kidney transplantation and waiting for an ABOc living donor kidney transplant or undergoing an ABOc deceased donor kidney transplant. Results were reported in the American Journal of Kidney Diseases [2020;76(5):616-623].

The study participants were 808 ABOi living donor kidney transplant recipients who were matched to 2423 controls; controls were identified from 245,158 adult first-time kidney-only waitlist registrants who did not receive an ABOi living donor kidney transplant and who remained on the waitlist or received either an ABOc living donor transplant or an ABOc deceased donor transplant from 2002 to 2017. The outcome of interest was death.

Cox proportional hazards regression and Cox models that accommodated for changing hazard ratios over time were used to compare mortality among ABOi living donor kidney transplant recipients versus a weighted matched comparison population.

Compared with the control group (general waitlist population), ABOi recipients were slightly younger at the first active date (median age 51 years vs 54 years), more likely to have private insurance, 67.2% vs 48.5%), more likely to list preemptively (52.7% vs 23.8%), less likely to be Black (18.2% vs 29.1%) or Hispanic (15.1% vs 17.2%), and more likely to have blood type O (70.4% vs 50.7%) (P<.001 for all comparisons).

At 30 days following living donor kidney transplantation, cumulative survival was lower in the ABOi group than in the matched controls receiving conservative therapy (99.0% vs 99.6%). At 1-year following living donor kidney transplantation, cumulative survival was comparable  between the two groups: 97.0% in the ABOi living donor recipient group versus 96.4% in the matched controls receiving conservative therapy.

However, at 5 and 10 years post procedure, cumulative survival was substantially higher for ABOi transplant recipients (90.0% vs 81.9% and 75.4% vs 68.4%, respectively). The increase in survival for transplant recipients in the ABOi group during the study period was statistically significant. During the observed follow-up time, results of a stratified Cox model showed a significant association between ABOi living donor kidney transplant and an average 25% lower mortality risk (hazard ratio, 0.67; 95% confidence interval, 0.53-0.84; P<.01).

Among the matched controls who did not undergo ABOi transplantation, median time to kidney transplantation, either living donor or deceased donor, was 4.2 years. Accounting for the competing risk of waitlist mortality, the cumulative incidence of kidney transplantation at 1, 3, and 5 years was 21.2%, 41.4%, and 53,7%, respectively. Accounting for the competing risk of kidney transplantation, cumulative risk of waitlist mortality at 1, 3, and 5 years was 3.3%, 10.8%, and 15.0%, respectively.

The researchers cited some limitations to the study findings, including the unavailability of desensitization regimens and methods to detect and measure ABO antibody titers, and not accounting for the possibility of kidney paired donation (KPD) due to unavailability of KPD registry status.

In conclusion, the researchers said, “We report that ABOi living donor kidney transplantation is associated with a substantial survival benefit compared with waiting for a compatible deceased donor organ. Although these findings are not surprising, we have quantified this survival benefit: ABOi living donor kidney transplantation confers an ~35% reduction in mortality over the long term compared with waiting for ABOc living donor kidney transplant or deceased donor kidney transplant. The survival benefit of ABOi living donor kidney transplant compared favorably with other types of kidney transplantations. ABOi living donor kidney transplantation remains a viable treatment option for patients with a willing  but incompatible living kidney donor.”

Takeaway Points

1. Researchers conducted a retrospective cohort study to examine the difference in patient survival between blood group ABO-incompatible (ABOi) living donor kidney transplantation and waiting for an ABO-compatible (ABOc) living or deceased donor transplantation.
2. In Cox proportional hazards regression and Cox models that accommodated for changing hazard ratios over time, compared with matched controls, there was an association between ABOi living donor kidney transplantation and greater mortality risk in the first 30 days following the procedure.
3. However, mortality was lower in the ABOi group than in the control group beyond 180 days post-transplantation. Patients in the ABOi group had higher cumulative survival at 5 and 10 years post-transplant compared with patients who remained on the waitlist or received an ABOc living or deceased donor transplant.