Chronic allograft nephropathy--clinical guidance for early detection and early intervention strategies

Improvements in reducing acute rejection rates following kidney transplantation in the last decade have not been mirrored by improvements in long-term graft survival rates [1,2]. One of the major causes of late graft loss in renal transplant recipients is chronic allograft nephropathy (CAN) [3–5] (Figure 1). CAN is highly prevalent in renal transplant recipients, with moderate to severe CAN present in 24.7% of recipients at 1 year post-transplant and in 89.8% of recipients by 10 years post-transplant [6]. CAN is defined by the histopathological features of interstitial fibrosis and tubular atrophy, but can also be associated with subclinical rejection, transplant glomerulopathy [6–8] or transplant vasculopathy caused by smooth muscle cell proliferation [4,9]. Therefore, the term CAN is being employed quite widely to describe a clinical syndrome instead of defining the presence of interstitial fibrosis or tubular atrophy. In order to avoid misinterpretations of this term, at the most recent ‘Banff’ meeting, it was proposed that pathologists no longer use this term, and simply refer to interstitial fibrosis and tubular atrophy (IF/TA) [10]. The term ‘chronic rejection’ has also been suggested as a possible replacement for CAN. However, this implies the pathology has an immune aetiology. As a pathological change often precedes any deterioration in function, the alternative term ‘chronic allograft dysfunction’ also has limitations. The revised Banff classification now recognizes chronic antibody-mediated rejection, in addition to IF/TA, broadening the underlying pathological lesions and pathophysiology of patients with