Chronic Allograft Nephropathy: The Mechanisms and Strategies

Chronic allograft nephropathy (CAN) is the main cause of long-term renal allograft loss. It is an active but slowly progressive injury mainly caused by alloreactivity to the graft, and further deteriorated by non-immunologic nonspecific factors. After an overview of the pathologic characteristics of CAN based on the Banff Working Classification, the underlying mechanisms and therapies are explored in this review, with an emphasis on novel theories and new findings. With regard to the mechanisms, indirect antigen presentation, ICOS-B7h costimulatory pathways, the roles of immune cells, humoral immunity, epithelial–mesenchymal transition and fibrogenesis are paid more attention than non-immunologic factors including calcineurin inhibitor (CNI) nephrotoxicity, ischemia/reperfusion, senescence and other various factors. With regard to therapeutic strategy, we line up the clinical and experimental proceedings based on the mechanisms. Sufficient immunosuppression, CNI sparing, rapamycin conversion, and administration of mycophenolate mofetil have been applied clinically and are discussed. New experimental therapies on deletion of humoral factors, blockade of costimulation pathway, intervention of fibrogenesis, blockade of signal transduction pathway, protection of endothelium and tissues, and induction of accommodation are introduced together with other nonspecific treatments. [Hong Kong J Nephrol 2007;9(2):58–69]