Background: Sensitization to HLA antigens is a major barrier to kidney transplantation. We sought to determine the etiology, incidence and outcomes of kidney transplants performed in highly sensitized patients.

Methods: We examined these questions in an analysis of the UNOS dataset involving all kidney transplants between 1997 and 2014. 7,542 highly sensitized patients (PRA ≥ 98%) were identified and compared to 108,736 non-sensitized patients (PRA=0).

Results: The number of highly sensitized patients waitlisted/year has increased over the study period 817 to 2150 patients/year. 56% of highly sensitized patients on the waitlist were re-transplants. Pregnancy was the only sensitizing event in 18% of patients, and transfusion was the only sensitizing event in 5%. 9% of highly sensitized patients had no cause reported. The average wait-time for highly sensitized patients was significantly longer than non-sensitized patients (511 +/-553 days vs 940 +/- 835 days, p=<0.001)). 17.4% of highly sensitized patients died on the waitlist compared to 11.6% of non-sensitized patients, p<0.001. The 10 –year actuarial graft survival for highly sensitized recipients was 43.9% compared to 52.4% for non-sensitized patients, p<0.001. Highly sensitized patients with a history of previous transplantation had worse actuarial 10-year graft survival (39.4% vs 46.7%, p=0.002). In multivariate analyses the combination of being highly sensitized and re-transplantation increased the risk of graft loss by 43% (HR 1.43, CI 1.33 – 1.52, p<0.001).

Conclusions: Highly sensitized patients make up a growing portion of the kidney transplant waitlist, with the majority being previous transplant recipients. Graft survival in the highly sensitized patient is significantly inferior to non-sensitized patients. Novel therapeutic strategies are needed to improve access to transplantation and long-term outcomes in kidney transplant candidates with a PRA ≥ 98%.

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