Donor-specific antibodies in kidney transplantation: the University of Wisconsin experience.

Abstract

Antibody-mediated rejection (ABMR) is the leading cause of allograft failure in kidney transplant recipients. This article provides a summary of the clinical research relating to donor-specific antibodies (DSA) and ABMR in kidney transplant recipients at the University of Wisconsin-Madison Transplant Center. Over 40% of the kidney transplant candidates on the UNOS waitlist are sensitized, and both preformed and de novo DSA are associated with increased risk of rejection and graft loss. We have developed graded induction-desensitization treatment and monitoring protocols based on the degree of immunologic risk. We have also implemented standard treatment and surveillance strategies for patients with ABMR. Additional important observations from our studies include high rates of ABMR in patients with positive C4d staining in postreperfusion biopsies and rise in DSA at 1 week after transplant, and increased risk of kidney allograft failure in patients with de novo DSA and ABMR, as well as in patients with HLA-DSA undetectable ABMR. We also found worse outcomes with de novo DSA following simultaneous pancreas--kidney and liver--kidney transplantation. Notably, favorable long-term graft outcomes were observed in patients with DSA who do not present the classic histopathological findings of ABMR. In order to improve long-term outcomes for kidney transplant recipients, further research focusing on the pathogenic mechanisms elicited by HLA and non-HLA DSA, and novel therapies targeting these pathways is needed.