Background.Antibody(Ab) against the angiotensin II receptor(AT1R) can cause antibody mediated rejection(AMR) and graft failure after transplantation. We evaluated whether circulating AT1R is a potential marker for AMR and graft outcome by comparing levels between patients who were AMR-free or had early or late AMR.

Methods. Blood from 73 Normals and 72 deceased donor renal transplant recipients who lacked DSA was tested. Pre- and serial posttransplant serums were tested for AT1R and AT1R-Ab. AT1R>60 pg/ml and AT1R-Ab>10 U/ml were considered elevated. Patients were divided into GpI (AMR-free, n=27), GpII (AMR< 1 yr, n=26) and GpIII (AMR> 1 yr, n=19). Three year outcomes were compared.

Results. AT1R was present in 20% Normals at low levels (13±26). In contrast, preoperative AT1R was highly elevated (367±537, p<.01) and universal (92%, p<.01) among patients. However, preoperative AT1R levels were equivalent between patient groups (p=ns) and didn't predict risk of AMR. Posttransplant AT1R levels initially declined in all groups and continued to decline among Gps. I and III to 88±10 (p<.01) and 20% incidence (p<.01) by 1-year. In contrast, AT1R spiked during AMR among GpII (p<.01), declined after treatment, but remained elevated (155±58, p<.01) among 50% patients (p<.01). Three year graft survival was superior (p<.01) for GpI vs. GpII or GpIII (100% vs. 70% and 45%). One-year AT1R levels were reexamined and were higher (p<.01) among failed vs. surviving grafts for GpII (209±90 vs. 75±90) and GpIII patients (171±267 vs. 38±50). The prevalence of concurrently elevated AT1R and AT1R-Ab was determined. Both GpII and III patients displayed elevated AT1R-Ab for all failed but also most surviving grafts (97% vs. 65%, p<0.01). However, elevated AT1R either without(69% vs.18%, p<.01) or with simultaneously elevated AT1R-Ab (66% vs. 9%, p<.01) was associated with increased risk of graft failure.

Conclusion. Circulating AT1R is uncommon among healthy individuals but universal among renal patients and may reflect ongoing tissue injury. Circulating AT1R levels increased during AMR which was likely mediated by AT1R-Ab in this study where patients lacked DSA. Persistently elevated AT1R at l-year, particularly when combined with elevated AT1R-Ab, indicated increased risk of graft failure and may be a useful marker to facilitate detection of subclinical or late AMR.

CITATION INFORMATION: Kimball P, Gupta G, McDougan F. Elevated Circulating AT1R Levels Indicate Heightened Risk for Antibody Mediated Rejection and Graft Failure. Am J Transplant. 2017;17 (suppl 3).

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