The Lancet, Early Online Publication, 23 November 2012
 Antibody-mediated vascular rejection of kidney allografts: a population-based study

Carmen Lefaucheur MD , Dr Alexandre Loupy MD, Dewi Vernerey MPH , Prof Jean-Paul Duong-Van-Huyen MD, Caroline Suberbielle MD, Dany Anglicheau MD, Jérôme Vérine MD, Thibaut Beuscart MPH, Dominique Nochy MD, Prof Patrick Bruneval MD, Prof Dominique Charron MD, Michel Delahousse MD, Jean-Philippe Empana MD, Prof Gary S Hill MD, Prof Denis Glotz MD, Prof Christophe Legendre MD, Prof Xavier Jouven MD

Summary
Background   Rejection of allografts has always been the major obstacle to transplantation success. We aimed to improve characterisation of different kidney-allograft rejection phenotypes, identify how each one is associated with anti-HLA antibodies, and investigate their distinct prognoses.

Methods   Patients who underwent ABO-compatible kidney transplantations in Necker Hospital and Saint-Louis Hospital (Paris, France) between Jan 1, 1998, and Dec 31, 2008, were included in our population-based study. We assessed patients who provided biopsy samples for acute allograft rejection, which was defined as the association of deterioration in function and histopathological lesions. The main outcome was kidney allograft loss—ie, return to dialysis. To investigate distinct rejection patterns, we retrospectively assessed rejection episodes with review of graft histology, C4d in allograft biopsies, and donor-specific anti-HLA antibodies.

Findings   2079 patients were included in the main analyses, of whom 302 (15%) had acute biopsy-proven rejection. We identified four distinct patterns of kidney allograft rejection: T cell-mediated vascular rejection (26 patients [9%]), antibody-mediated vascular rejection (64 [21%]), T cell-mediated rejection without vasculitis (139 [46%]), and antibody-mediated rejection without vasculitis (73 [24%]). Risk of graft loss was 9·07 times (95 CI 3·62—19·7) higher in antibody-mediated vascular rejection than in T cell-mediated rejection without vasculitis (p<0·0001), compared with an increase of 2·93 times (1·1—7·9; P=0·0237) in antibody-mediated rejection without vasculitis and no significant rise in T cell-mediated vascular rejection (hazard ratio [HR] 1·5, 95% CI 0·33—7·6; p=0·60).

Interpretation   We have identified a type of kidney rejection not presently included in classifications: antibody-mediated vascular rejection. Recognition of this distinct phenotype could lead to the development of new treatment strategies that could salvage many kidney allografts.