H. Regele et al., Endothelial C4d deposition is associated with inferior kidney allograft outcome independently of cellular rejection, NEPH DIAL T, 16(10), 2001, pp. 2058-2066
Background. Capillary deposition of complement split product C4d has been s
uggested to be a valuable marker for humoral rejection. In this retrospecti
ve study we evaluated the clinical impact of C4d deposition in renal allogr
afts with special emphasis on associations between C4d staining patterns an
d histological features of acute rejection.
Methods. One hundred and two allograft biopsies obtained from 61 kidney tra
nsplants (1-532 days after transplantation, median 14 days) were examined b
y immunohistochemistry on routine paraffin sections using a novel anti-C4d
polyclonal antibody (C4dpAb).
Results. Fourty-two of 102 biopsies showed endothelial C4d deposits in peri
tubular capillaries (PTC). Histopathological analysis revealed a significan
tly lower frequency of positive C4d staining in biopsies with rather than i
n those without acute cellular rejection defined by the Banff grading schem
a (P <0.01). For clinical evaluation, patients were classified according to
C4d staining in allografts C4d(PTC) positive in at least one biopsy, n=31
vs C4d(PTC)( negative in all biopsies, n = 30). C4d(PTC) positive patients
had significantly higher serum creatinine levels than C4d negative patients
. Even in the absence of morphological evidence for rejection, differences
in serum creatinine levels between C4dPTC positive and negative recipients
were significant (6 months: 2.01 +/- 0.75 rs 1.41 +/- 0.27 mg/dl; 12 months
: 1.95 +/- 0.60 vs 1.36 +/- 0.34 me dl, 18 months: 1.98 +/- 0.50 vs 1.47 +/
- 0.31 mg, dl. P <0.05). All patients with rejection resistant to conventio
nal therapy (n=4) were in the C4d(PTC) positive subgroup. All recipients wi
th panel reactive antibodies (PRA) > 50% (n = 8) were C4dPTC positive.
Conclusions. Our data indicate that endothelial C4d deposition is associate
d with inferior graft outcome. We provide evidence that this immunohistoche
mical finding and its clinical impact are not associated with morphological
signs of cellular rejection.