Mechanisms of ageing in chronic allograft nephropathy

Denis Susa, Ron W.F. De Bruin*, Jay R. Mitchell, Henk P. Roest, Jan H.J. Hoeijmakers, Jan N.M. Ijzermans

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

1 Citation (Scopus)


Background. Chronic allograft nephropathy (CAN) is the single most important cause of late graft loss. Histologic signs of CAN overlap with the histology of normally ageing kidneys. Clinical observations show an inverse relationship between either donor age or ischemia time and long-term graft survival. The mechanisms by which donor age or ischemia lead to reduced functional lifespan are currently unknown. Material and methods. A review of the current literature on renal transplantation, ageing mechanisms and advances in the molecular pathogenesis of CAN was performed. Results and conclusions. Ischemia time and donor age have been identified as major allo-antigen- independent risk factors. Following transplantation, reactive oxygen species cause oxidative DNA and telomeric damage. Evidence for a molecular connection between oxidative DNA damage and ageing has increased, and suggests that the mechanisms causing normal ageing and long-term organ dysfunction may be fundamentally the same. The accelerated appearance of ageing phenotypes in transplanted organs has been shown in several studies. Together with the deleterious ongoing allogeneic immune response of the recipient, this leads to accelerated exhaustion of the regenerative capacity of the kidney, and eventually to dysfunction of the renal allograft.

Original languageEnglish
Pages (from-to)7-17
Number of pages11
JournalJournal of Organ Dysfunction
Issue number1
Publication statusPublished - 2007


Dive into the research topics of 'Mechanisms of ageing in chronic allograft nephropathy'. Together they form a unique fingerprint.

Cite this