Histological and immunohistochemical analyses were made of biopsy spec
imens from 50 consecutive patients who experienced putative graft reje
ction, The mean age of the patients was 44.5 years (range, 17-69 years
) and 26 were men. There were 67 evaluable allograft specimens, which
were grouped according to the histological diagnosis: group 1, acute t
ubulointerstitial rejection (n=42); group 2, acute vascular rejection
(n=18); and group 3, diffuse thrombosis (n=7), Over a follow-up period
of 21-57 months, the mean number of rejection episodes was 1.7, 2.8,
and 3.3 in groups 1, 2, and 3, respectively, Allograft loss occurred i
n 7 out of 30, 10 out of 16, and 4 out of 4 patients in groups 1, 2, a
nd 3, respectively. The following histological parameters differed sig
nificantly (P<0,05) among the groups: interstitial edema, congestion o
f peritubular capillaries, glomerular thrombosis, and glomerular ische
mia (group 3 > group 2 > group 1). Interstitial bleeding was seen more
often in group 2 and 3 tissues than in group 1 specimens (P<0,01), Im
munohistochemical analyses showed that vascular rejection was associat
ed with WT14 staining for monocytes and macrophages around the tubuli
and with interstitial deposition of complement factor 3, With regard t
o serology, positive anti-endothelial cell antibody-dependent cellular
cytotoxicity was associated with vascular rejection and thrombosis of
the graft in all patients tested, and with graft loss in 75%. Pre-exi
stent positive anti-IgG immunofluorescence on peritubular capillaries
in pretransplant biopsy specimens incubated with patient serum was fou
nd in only 3 of the 50 patients, but was associated with graft loss in
2 of the 3. Cytomegalovirus infection was associated with a higher pe
rcentage of graft loss, There were significant intergroup differences
in panel reactive antibodies before transplantation (P<0,001), with hi
gher titers in groups 2 and 3, The findings in relation to interstitia
l rejection are compatible with cellular rejection, while the data on
vascular rejection support a humorally mediated pathogenesis.