Acute graft loss secondary to necrotizing vasculitis: Evidence for cytokine-mediated shwartzman reaction in clinical kidney transplantation

A small number of kidney transplant recipients abruptly lose function secondary to acute renal artery or vein thrombosis or more rarely a form of necrotizing vasculitis. We report a group of four kidney transplant recipients who lost renal function and share the following features: (1) diabetes (type I, insulin-dependent diabetes mellitus, type II or steroid-induced); (2) abrupt change/loss of renal function; (3) a concomitant clinical event (fever, viral symptoms, menometrorrha-gia, viremia, bacteremia); (4) severe necrotizing vasculitis with hemorrhagic necrosis on histopathology; (5) patent renal artery and vein at time of transplant nephrectomy (i.e., no vascular thrombosis); and (6) high levels of peripheral serum γ-IFN 1-5 days before transplant nephrectomy (467±175 pg/ml) compared with that of patients experiencing severe rejection (8.4±3.7 pg/ml) (P<0.002). These data support the concept of a cytokine (IFN-γ)-mediated accelerated inflammatory response resulting in graft loss from necrotizing vasculitis—the clinical equivalent of an organ-specific Shwartzman reaction.