The main causes of the late dysfunction of renal allografts are chronic rejection
and chronic transplant nephropathy. Both are clinicopathologic entities, with a similar
clinical presentation, but different histologic appearances. Chronic rejection is
characterized by the presence of alloantigen-induced lesions (transplant arteriopathy
and transplant glomerulopathy), and chronic transplant nephropathy by nonspecific
sclerosing changes. The incidence of transplant arteriopathy and transplant glomerulopathy
is relatively low. Electron microscopy (EM) may overcome the limitations In the histologic
diagnosis of chronic rejection, because It verifies alloantigen-Induced chronic microvasculopathy
in the peritubular capillaries (transplant capillaropathy), and identifies transplant
glomerulopathy more precisely than does fight microscopy. To assess the value of EM
in chronic rejection diagnosis, a retrospective search for transplant capillaropathy
and transplant glomerulopathy was performed In a consecutive series of 91 biopsies
performed; greater than or equal to6 months after Implantation (median: 26 months,
range 6-186) and the diagnoses were reclassified on the basis of the ultrastructural
findings. The definitions used were: transplant capillaropathy: a peritubular capillary
profile with seven or more circumferential basement membrane layers, or at least three
profiles with five or six circumferential layers; ultrastructurally verified transplant
glomerulopathy: thickening of the capillary wall in at least three loops in consequence
of the widening of the subendothelial space by abnormal basement membrane material,
and the formation of a new layer(s) of basal lamina; and chronic rejection: the presence
of transplant capillaropathy and/or transplant glomerulopathy and/or transplant arteriopathy.
Histologically, chronic transplant nephropathy, chronic rejection, chronic cyclosporine
nephrotoxicity, glomerulonephritis, acute rejection, "suspicious" for acute rejection,
and "others" were diagnosed In 37%,34%,21%,19%,57%,30%, and 5% of the specimens, respectively.
The results of EM increased the diagnosis of chronic rejection to 69% of the cases,
and decreased chronic transplant nephropathy to 15%. The individual incidence of transplant
capillaropathy and transplant glomerulopathy was 79% and 57%, respectively, and their
cumulative incidence was 92%. Five biopsies exhibited merely transplant arteriopathy.
A late dysfunction typically had more than one cause; the most frequent combination
was chronic rejection and acute rejection. In conclusion, the EM search for transplant
capillaropathy and transplant glomerulopathy doubled the frequency of the diagnosis
of chronic rejection. Currently, the evaluation of renal allograft biopsies from recipients
with a late dysfunction relies on standard light microscopy. Because fight microscopy
per se proved to be insensitive in the diagnosis of chronic rejection, incorporation
of EM into the evaluation of late dysfunction biopsies is strongly recommended.
