Chronic renal allograft dysfunction.
The major causes of renal transplant loss are death from vascular, malignant or infectious disease, and loss of the allograft from chronic renal dysfunction associated with the development of graft fibrosis and glomerulosclerosis. Chronic allograft nephropathy (CAN) is the histologic description of the fibrosis, vascular and glomerular damage occurring in renal allografts. Clinical programs rely on monitoring change in serum creatinine for identification of patients at risk of CAN, but this change occurs late in the course of the disease, and underestimates the severity of pathologic change. CAN has several causes: ischemia-reperfusion injury, ineffectively or untreated clinical and subclinical rejection, and superimposed calcineurin inhibitor nephrotoxicity, exacerbating pre-existing donor disease. Once established, interstitial fibrosis and arteriolar hyalinosis lead to progressive glomerulosclerosis over the subsequent years. There have been a number of approaches to treatment aimed at reducing the impact of CAN, mostly centered around avoidance of calcineurin inhibitors through their elimination in all, or just selected, patients. These immunosuppression strategies combine corticosteroids with azathioprine or mycophenolate mofetil, and/or sirolimus and everolimus. Late identification of CAN in individual patients has meant that strategies for intervening to prevent chronic renal allograft dysfunction and subsequent graft loss tend to be "too little and far too late."
Chapman
Jeremy R
JR
Department of Renal Medicine, Westmead Hospital, Westmead, New South Wales 2145, Australia. jeremy_chapman@wsahs.nsw.gov.au
O'Connell
Philip J
PJ
Nankivell
Brian J
BJ
D002908:Chronic Disease; D005355:Fibrosis; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000473:pathology; D017211:Treatment Failure