Pathophysiology and treatment options of chronic renal allograft damage

Chronic rejection is a poorly understood entity albeit a frequent cause of graft failure. Despite the advent of new immunosuppressive agents, neither the slope of graft destruction nor the frequency is ameliorated. There are a number of hypothesis which try to explain the conundrum of chronic graft destruction: ongoing rejection, antibody-mediated rejection, poor choice of organs, hyperfiltration, calcineurin inhibitors (CNI) nephrotoxicity and non-compliance among them. None of these hypotheses can explain all features of the process, thus, it is likely that they act in combination. What seems to be clear is a beneficial effect of early angiotensin-converting enzyme (ACE)/AT1 blocker treatment. It is less clear, however, whether a reduction or a switch from CNIs to other immunosuppressants prolongs graft survival. This review highlights the pathophysiological aspects that are important for the development of chronic allograft damage in the context of possible treatment options.