Longitudinal analysis of chronic allograft nephropathy: clinicopathologic correlations.
BACKGROUND
Loss of the allograft from chronic allograft nephropathy and death of the patient from vascular, malignant, or infective disease are the major problems in renal transplantation today. Protocol biopsy of the long-term kidney has provided new data with which to develop strategies for prevention and treatment of chronic allograft nephropathy.


METHODS
Two series of long-term protocol biopsies are reviewed. In the first, renal biopsies were obtained at time 0, and at 3 months and 12 months, and the recipients of the renal allografts were followed up for up to 15 years. In the second, the kidneys of recipients of simultaneous pancreas kidney transplants were biopsied annually for 10 years, and the results correlated with clinical events.


RESULTS
Chronic allograft nephropathy is caused by acute and chronic immune-mediated damage, as well as by chronic calcineurin inhibitor nephrotoxicity. Both immune and nonimmune mechanisms exacerbate pre-existing donor disease and ischemia-reperfusion injury. Established interstitial fibrosis and arteriolar hyalinosis lead to progressive glomerular sclerosis and eventual loss of the graft.


CONCLUSIONS
Protocol biopsies have shown that clinical parameters of renal function underestimate the severity of chronic graft damage. Strategies for preventing or treating chronic renal allograft dysfunction and subsequent graft loss must better control rejection and simultaneously avoid nephrotoxicity.
Chapman
Jeremy R
JR
Centre for Transplant and Renal Research, Department of Renal Medicine, Westmead Hospital, University of Sydney, Sydney, Australia. jeremy_chapman@wsahs.nsw.gov.au
D001706:Biopsy; D019703:Calcineurin / Q000502:physiology; D065095:Calcineurin Inhibitors; D002908:Chronic Disease; D003404:Creatinine / Q000097:blood; D005355:Fibrosis; D005919:Glomerular Filtration Rate; D005923:Glomerulosclerosis, Focal Segmental / Q000503:physiopathology; D006801:Humans; D007668:Kidney / Q000473:pathology* / Q000503:physiopathology; D007674:Kidney Diseases / Q000209:etiology* / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology; D008137:Longitudinal Studies; D016035:Pancreas Transplantation; D015427:Reperfusion Injury; D012306:Risk; D013997:Time Factors; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000276:immunology
D065095:Calcineurin Inhibitors; D003404:Creatinine; D019703:Calcineurin