Early Acute Rejection (AR) Initiates Alloimmune Mechanisms Ultimately Leading to Kidney Graft Failure
Nephrology,Transplant Center, Mayo Clinic, Rochester, MN
Surgery, Transplant Center, Mayo Clinic, Rochester, MN
Meeting: 2013 American Transplant Congress
Abstract number: 46
Introduction: AR increases risk of kidney allograft failure. The exact process by which AR leads to graft loss is yet unclear. We examined the causes of graft loss beyond one year in patients with/without AR during first year post-transplant (AR1y).
Methods: Included are 1650 adult, crossmatch negative recipients transplanted between 1998-2010; age 52±14 years; 61% male; 76% living donor recipients; f/u 74±41 months. 77% received thymoglobulin induction and 85% triple immunosuppression including tacrolimus. Death-censored graft loss (GL) was classified as alloimmune (AR, chronic antibody mediated rejection (cAMR)) and non-alloimmune (recurrent disease, non-alloimmune fibrosis/atrophy and medical). Donor specific antibodies (DSA) measured pre-transplant and at 1 year.
Results: 245 of 1650 recipients had AR1y (15%), including 30% borderline, 64% types 1 or 2 and 6% acute AMR. There were 171 GL (12%) after 1 year. AR1y increased the risk of GL (HR=2.39 (1.72-3.33), p<0.0001) even after censoring for DSA pre-transplant (HR=2.04 (1.07-3.92), p=0.03). Compared to no AR1y, those with AR1y had more alloimmune GL (35% vs 62%, p<0.0001). For example, cAMR accounted for 19% of all GL in patients without AR1y and 40% in patients with AR1y (p<0.0001). Of interest, the increased risk of cAMR was present in patients wihout pre-transplant DSA and in those without acute AMR. To explore why AR1y increases the risk of cAMR in DSA- recipients,we assessed new DSA at 1 year. De novo DSA class II was more common in patients with AR1y than in those without (21% vs 10%, p=0.007) but new DSA I was not increased. Protocol biopsies at 1 year identified those patients at risk of alloimmune GL post-AR1y. Thus, compared to patients without AR1y and with a normal biopsy, patients with normal post-AR1y biopsies (19%) had no increased risk of GL. In contrast, patients with persistent inflammation+fibrosis post-AR1y (33%) had a marked increased risk of alloimmune GL (HR=9.84 (3.97-24.4), p<0.0001).
Conclusions: Early acute rejection, even in the absence of DSA pre-transplant, increases the risk of alloimmune GL commonly due to cAMR. We postulate that this is due to new DSA class II formation after AR particularly in grafts with persistent inflammation after AR. Current approach to AR therapy needs to be reconsidered as frequently, AR triggers pathogenic events that ultimately may lead to graft loss.
To cite this abstract in AMA style:
Ters MEl, Keddis M, Rodrigo E, Muriithi A, Stegall M, Cosio F. Early Acute Rejection (AR) Initiates Alloimmune Mechanisms Ultimately Leading to Kidney Graft Failure [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/early-acute-rejection-ar-initiates-alloimmune-mechanisms-ultimately-leading-to-kidney-graft-failure/. Accessed October 6, 2024.« Back to 2013 American Transplant Congress