Introduction. Death-censored graft loss (GL) is generally analyzed as a single endpoint. However, GL has multiple causes, alloimmune (GLA, acute rejection, chronic antibody rejection) and non-alloimmune (GLNA, recurrent disease, medical illness, etc.). We postulated that assessing GLA/GLNA separately may reveal previously unrecognized associations of clinical significance.
Methods. Included are 1491 crossmatch negative, adult, kidney recipients from 1996-2007; age 50.7±14; 73% living donors; follow up 84.4±44 months. 77% received thymoglobulin induction and triple immunosuppression (tacrolimus, 76%).
Results. There were 281 GL (19%): 37 (2%) primary non-function, 13 (1%) unknown cause, 97 GLA (7%) and 134 GLNA (9%). Compared to 1996-99 transplants, the risk of GLA declined after 2005 (p=0.048) while the risk of GLNA declined throughout the study period (p=0.001). Table shows variables associated with GLA/GLNA (multivariate). GLA risk declined with increasing recipient age: at 5/10 years GLA were 7.6/17.5% in recipients<40 (N=359) and 1.2/4.6% in those>60 (N=420). Increasing recipient age reduced the impact of GLA risk factors: compared to no DSA, recipients with DSA-II pre-transplant (N=104) and age>50 (N=51) had no increased risk of GLA (p=0.899) while GLA risk increased progressively with decreasing recipient age<50 (p=0.013). Similarly, compared to no acute rejection (AR), AR in recipients age>50 did not increase GLA risk (p=0.135) while in younger recipients AR related to markedly increased GLA risk (p<0.0001). These associations were not aparent when GL was considered as a single endpoint. Increasing donor age related to GLNA (table) due to graft fibrosis/atrophy (HR=1.55, p=0.032) and marginally to GL during medical illness (p=0.072).
Conclusions. Analyses of risk factors for GLA/GLNA suggest that these are distinct events. Analyses revealed previously unappreciated powerful protective effects of recipient age against alloimmune injury. Analyses of GL by cause helps understand risk factors for graft loss and suggests new management strategies.
|Recipient age||0.56 (0.52-0.60) p<0.0001||p=0.356|
|HLA mismatches||1.35 (1.13-1.62) p=0.001||p=0.087|
|DSA class II||2.53 (1.23-5.22) p=0.012||p=0.279|
|Transplant number||1.76 (1.16-2.68) p=0.008||p=0.815|
|Donor age||p=0.078||1.35 (1.29-1.41) p<0.0001|
|Donor type||p=0.163||1.43 (1.19-1.71) p<0.0001|
To cite this abstract in AMA style:Cosio F, Rodrigo E, Ters MEl, Chopra B, Lorenz E, Stegall M. Alloimmune and Non-Alloimmune Kidney Graft Losses, Improving Our Understanding of Factors Associated with Failure [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/alloimmune-and-non-alloimmune-kidney-graft-losses-improving-our-understanding-of-factors-associated-with-failure/. Accessed October 26, 2020.
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