Abstract

Chronic allograft nephropathy is the major cause of late renal allograft loss. This disease is heterogeneous and the diagnosis is nonspecific, with both immune and nonimmune causes. Increasingly, we are able to recognize specific contributors to the disease. Further understanding of chronic allograft nephropathy comes from a large study detailing the natural history of the disease, from protocol biopsies revealing subclinical cellular rejection, and from studies using C4d staining to distinguish antibody-mediated chronic rejection from nonspecific causes. Also made more clear are nonimmune mechanisms of chronic allograft nephropathy, such as the effect of decreased dosing of calcineurin inhibitors, and the concept of senescence as a mechanism of the disease. Chronic allograft nephropathy is a heterogeneous disease with immune and nonimmune causes. Some features recognizable by histology and detected by other laboratory tests can help to categorize specific causes of the disease in particular cases. In addition, recent studies have contributed to our knowledge of the pathogenesis of the disease. In order to advance our understanding, we must be able to distinguish the various recognizable causes of chronic allograft dysfunction. Further research is warranted on the subset of the disease with indeterminate cause.

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