Accelerated rejection, thrombosis, and graft failure with angiotensin II type 1 receptor antibodies

Angiotensin II type 1 receptor antibodies (AT(1)R-Abs) have been implicated in renal transplant rejection and failure; however, the mechanism of allograft damage, patterns of clinical presentation, and response to desensitization of AT(1)R-Abs have not been clearly established. We present the case of a 7-year-old boy with preformed AT(1)R-Abs who developed accelerated vascular and cellular rejection and renal allograft thrombosis despite desensitization and treatment with angiotensin receptor blockade. Although an association between AT(1)R-Abs and microvascular occlusion has been previously described, we are the first to describe an association between AT(1)R-Abs and renal artery thrombosis, leading to devastating early allograft failure. This case highlights the risk of allograft thrombosis associated with AT(1)R-Abs and illustrates that previous treatments utilized for AT(1)R-Abs may not always be effective. Further studies are needed to better characterize the mechanisms of AT(1)R-Ab pathogenesis and to establish safe levels of AT(1)R-Abs both pre- and post-transplantation. Given the outcome of this patient and the evidence of pro-coagulatory effects of AT(1)R-Abs, we suggest that the presence of AT(1)R-Ab may be a risk factor for thrombosis. The role of treatment with anti-coagulation and novel immunomodulatory agents such as tocilizumab and bortezomib require further investigation.