Background. Antibody mediated rejection is the leading cause of renal allograft failure. Membrane-bound angiotensin II receptor(AngII) in the renal allograft can be a target of cellular(ACR) or antibody(AMR) mediated rejection. We questioned whether AngII was released during rejection and might be a useful marker of graft injury and outcome.

Methods. Serum was collected at 0,3,6, 12 months posttransplant from 53 renal transplant recipients and 20 healthy volunteers(Controls). Patients were grouped as: 27 Non-rejectors (NR), 9 ACR and 17 AMR occurring in first year. AngII was measured by elisa. Three year outcomes were compared.

Results. AngII was low among Controls(13±25 pg/ml). Using 60 pg/ml as upper limit, 20% Controls were above limit. In contrast, 90%(p<0.001) renal patients had >60 pg/ml AngII. Pretransplant levels were highly elevated(369±448, p<0.001) compared to Controls but similar between NR and all rejectors (367±537 vs. 372±356, p=ns) and between ACR and AMR groups(427±166 vs. 386±12, p=ns). Among NR, AngII levels and frequency of patients with >60 pg/ml continually declined and at l yr were similar to Controls(88 pg/ml, 20% patients, p=ns). In contrast, AngII levels spiked among rejectors during rejection. Thereafter, AngII level declined among ACR and 1-yr level(96 pg/ml) and frequency(37%) were similar(p=ns) to NR. In contrast, 1-year AngII levels(155 pg/ml) and frequency(50%) among AMR group were greater(p<0.01) than NR. Three year graft survival was equivalent between NR and ACR groups(100% vs. 90%, p=ns) but poor for AMR(60%, p=0.002). One-year AngII levels were reexamined among AMR patients with graft failure(n=7) or surviving grafts (n=10) at 3-years. Among graft-survivors, 1-yr AngII level(75±90 pg/ml) and above-normal frequency(30%) were equivalent (p=ns) to NRs. In contrast, patients with subsequently failed grafts had greater AngII(209±118, p<0.05) and a high frequency of patients with abnormal AngII levels(86%, p<0.05).

Summary. Circulating AngII is uncommon among healthy individuals but prevalent in renal failure. Pretransplant AngII levels didn't predict the potential for rejection. AngII spiked during both ACR and AMR. However, only sustained elevations in AngII after AMR were associated with poorer 3-year graft survival. This suggests systemic AngII may be a marker of tissue injury and may facilitate detection of subclinical or chronic antibody mediated rejection.

CITATION INFORMATION: Kimball P, McDougan F, Gupta G. Circulating Angiotensin II Receptor: Possible Marker for Antibody Mediated Tissue Injury? Am J Transplant. 2016;16 (suppl 3).

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