Chronic allograft failure: a disease we don't understand and can't cure?

Abstract

Keywords: donor; kidney transplant; nephropathy;recipientDuring recent decades many new and successfulstrategies have been developed to improve 1-yearrenal allograft survival rates. It has become evident,however, that graft loss after the first year has not beenreduced by the same magnitude. A high percentageof transplanted kidneys develop dysfunction in thefirst few months post-transplantation and ultimatelyfail, despite the use of modern immunosuppressiveregimens. This type of graft failure has been termedchronic rejection. However, as both immune and non-immune mechanisms seem to contribute to its patho-genesis, the term currently used is chronic allograftnephropathy (CAN). The concept of chronic rejectionslowly emerged in the 1950s and 1960s. Acute rejectionwas well known in the late 1950s, but even then onlyfew kidneys survived for months. Initially Hume et al.[1], and later Porter et al. [2] and Jeannet et al. [3],reported arterial intimal fibrosis and obliteration inrenal allografts in the late postoperative period, aprocess thought to be alloantibody mediated. Thislesion with vascular predominance, already presentin the very early stages, is now rare, even though theHume–Porter–Jeannet syndrome remains the basisof the current animal models of chronic rejection,thus limiting their relevance for the human CANproblem [4]. It therefore remains questionable whethersome findings obtained in animal models, such as thereversibility of chronic rejection as described by Tulliuset al. [5] in the F344-Lewis model, can be reproducedin the human setting.It is the major aim of this article to categorize (in theform of specific entities) the variety of factors that havebeen associated with human CAN. Finally, we willattempt to summarize the ideas of several authors on apotential common pathway that may link the diverserange of insults leading to functional and structuraldamage of kidney allografts.