Necrotizing crescentic glomerulonephritis--a conditional knockout model discloses new therapeutic challenges

Necrotizing extracapillary glomerulonephritis is considered the histological hallmark of pauci-immune renal vasculitis, a potentially life-threatening condition, in which glomerular involvement is mostly rapidly progressive [1]. A timely therapeutic intervention is mandatory to avoid the establishment of endstage renal disease in a short period of time. First-line treatment consists of steroids and immunosuppressive drugs at high dosages that have radically improved the disease’s prognosis, but that remain charged by frequent relapses, the appearance of side-effects, and do not obtain remission in 10% of the cases, with dramatic consequences for the patient [2]. Circulating anti-neutrophil cytoplasmic autoantibodies (ANCAs), present in about 90% of the cases, have been implicated in the pathogenesis of the disease most convincingly by Xiao et al. [3], whereas a compelling pathogenetic hypothesis is still missing for either ANCA-negative cases or for situations in which remission is accompanied by the persistence of high