Proteomic Portrayal of Transplant Pathologies

Abstract

Despite recent improvements in 1-yr outcomes for kidney transplantation, long-term allograft survival has not changed significantly in the past several decades.1 The survival half-life for kidneys from deceased donors is approximately 11 yr, and the pathogenesis of these late graft losses is multifactorial.2 Analyses of graft histology reflected in the revised Banff criteria indicate chronic allograft injury can be subcategorized, in part, on the basis of evidence of local inflammation and the presence or absence of interstitial fibrosis and tubular atrophy (IF/TA).3 Although specific inciting factors are difficult to define in each situation, distinct histopathologic entities often correlate with likely causes. For example, calcineurin inhibitor toxicity frequently manifests as IF/TA without inflammation; ongoing cellular alloimmunity presents histologically with tubulitis with or without IF/TA; C4d staining suggests transplant glomerulopathy with or without IF/TA; and detectable, donor-specific serum antibodies underlie antibody-mediated allograft injury.3 Because only a subset of patients develop chronic injury and because at present physicians do not have the ability to reverse chronic fibrotic kidney damage, it is essential that the transplant community develop reliable and noninvasive approaches to predict which patients are most likely to develop graft failure so that appropriate interventions can be instituted …