Pretransplant angiotensin II type 1-receptor antibodies point to an increase in renal graft sub-intimal fibrosis in living- donor kidney transplant recipients

The association between anti-AT1Rabs and microvascular injury observed in antibody-mediated rejection has been described in kidney graft Biopsies (KGBx). Methods: We herein describe the histopathologic findings of KGBx performed during the first year of transplantation (Tx) in 134 patients tested for pre-Tx anti-AT1Rabs in cryopreserved sera (04/2009 to 09/2013). Protocol KGBx before implantation (time-zero), 1 year after Tx and for cause KGBx were included. 21/134 Tx patients were anti-AT1Rab positive (>= 17 U/mL); 7/21 experienced acute rejection. For comparison a control group with anti-AT1Rabs < 17 U/mL, with (n = 16) and without (n = 31) acute rejection was included. Results: Preimplantation KGBx showed no differences in inflammatory and chronic findings, nor in subintimal fibrosis (25 vs 12.8%, p = .42) between patients with anti-AT1Rabs >= 17 U/mL and those with < 17 U/mL. Follow-up KGBx revealed a significantly greater proportion of arterial sub-intimal fibrosis (52.3 vs. 27.6%, p = .049) and extension (15.7 vs. 5.3, p = .015) in anti-AT1Rabs >= 17 U/mL compared to anti-AT1Rabs < 17 U/mL KGBx. No differences were observed in microcirculation inflammation, nor in interstitial fibrosis or tubular atrophy between groups. Also, anti-AT1Rabs >= 17 U/mL (beta 10.1, 2.3 to 17.8, p = .012) and more importantly anti-AT1Rabs >= 30 U/mL (beta 12.1, 3.1 to 20.9, p < .01), were independent risk factors associated with vascular occlusion resulting from sub-intimal fibrosis. Conclusion: Our study findings have shown that anti-AT1Rab values >= 17 U/mL are significantly associated to sub-intimal fibrosis and a greater percentage of vessel occlusion in kidney graft biopsies obtained during the first year posttransplant, particularly in coexistence with inflammation and de novo DSA.