Introduction. One year protocol biopsies (PBx) distinguish a large group of grafts with normal histology/mild fibrosis (GIF) and low risk of failure (LwR) from a smaller group of grafts with moderate/severe GIF, inflammation, or chronic antibody-mediated rejection (cAMR) that have high risk (HiR). We investigated causes of graft loss in LwR and HiR and the relationship between 1 year histology and cause of long term death-censored graft loss (GL).
Methods. Included are 818 negative crossmatch, adult recipients of transplants from 1998-2008 with 1 year PBx. Age 52±14; 73% living donors; f/u 84±37 months. Grafts with recurrent disease at 1 year were excluded. 78% received thymoglobulin induction and 85% triple immunosuppression with tacrolimus. GL were classified as alloimmune (GLA, acute rejection (AR) or cAMR) or non-alloimmune (recurrent disease, medical illness, etc.).
Results. At 1 year, 625 of 818 grafts (76.4%) were LwR. Compared to LwR, HiR had higher risk of GL beyond year 1 [HR=6.45 (4.24-9.82), p<0.0001] independently of graft function, AR, HLA mismatches (HLAmm) or donor specific antibodies (DSA). 34 of 95 GL (36%) occurred in LwR and 61 (64%) in HiR. HiR had markedly increased risk of GLA [HR=13.3 (6.60-26.8), p<0.0001). For example, cAMR caused 15% of GL in LwR and 43% in HiR (p<0.0001). In patients with high immunologic risk (i.e. DSA pre-transplant, HLAmm>3, re-transplants, AR) PBx histology also related to risk of GL. Thus, compared to patients without DSA, GLA was markedly increased in patients with DSA and HiR but not in those with DSA and LwR. Similarly, in patients with HLAmm>3, retransplants or AR the risk of GL was increased only in those with HiR in 1year PBx. Of interest, the percent of HiR grafts has declined progressively over time (OR=0.89 (0.84-0.95), p<0.0001) and consequently the %LwR grafts increased from 69.4% to 84.2% since 1998 to present.
Conclusions. Clinical/subclinical noxious events during the 1st year post-transplant result in changes in 1 year graft histology that predicts future risk of alloimmune GL. Still, a relatively large number of low risk grafts are lost largely due to non-alloimmune causes. One year graft histology is a modifiable endpoint that measures success of therapy during the 1st year and predicts future risk of alloimmune graft loss.
To cite this abstract in AMA style:El M, Cornell L, Rodrigo E, Keddis M, Muriithi A, Stegall M, Cosio F. Histology One Year Post-Kidney Transplant Relates to Risk of Alloimmune-Mediated Graft Failure Long Term [abstract]. Am J Transplant. 2013; 13 (suppl 5). http://atcmeetingabstracts.com/abstract/histology-one-year-post-kidney-transplant-relates-to-risk-of-alloimmune-mediated-graft-failure-long-term/. Accessed November 19, 2017.
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