Peritubular capillary C4d deposition and renal outcome in post-transplant IgA nephropathy.
BACKGROUND
Immunological staining of the transplanted kidney for C4d in peritubular capillaries (C4d(PTC)) has emerged as a useful method to detect antibody-mediated rejection in situ. In this retrospective study, we evaluated the prevalence of C4d(PTC) deposition in allograft renal biopsies diagnosed of IgA nephropathy (IgAN) and analysed its clinical significance.


METHODS
Sixty-six biopsy specimens of post-transplant IgAN, which were obtained to evaluate azotemia and/or heavy proteinuria, were examined by immunohistochemical staining of the paraffin sections with polyclonal antibody for C4d.


RESULTS
C4d was stained positively in peritubular capillaries in 16 (24%) of the 66 cases. The C4d(PTC)-negative (n=50) and C4d(PTC)-positive groups (n=16) were not different in recipient gender, age, donor age, type of donor (living vs. cadaveric), interval from transplantation to graft biopsy (41.6+/- 21.8 vs. 48.3+/-26.1 months) and post-biopsy follow-up period (60.3+/-23.3 vs. 56.9+/-25.4 months). During the follow-up period, 12 of 50 (24%) although the incidence of graft failure was not different by the C4d deposition in peritubular capillaries, intervals from renal biopsy to graft failure tended to be shorter in C4d(PTC)-positive cases than C4d(PTC)-negative cases. In Kaplan-Meier analysis, the renal allograft function of the C4d(PTC)-positive group deteriorated more rapidly than that of the C4d(PTC)-negative group (p<0.05). Histologically, the C4d(PTC)-positive group had findings suggestive of acute cellular rejection more commonly than the C4d(PTC)-negative group (p<0.01).


CONCLUSIONS
Evidence of humoral rejection, as demonstrated by C4d(PTC) deposition, was concurrently present in significant portions of post-transplant IgAN biopsy specimens and was associated with more rapid deterioration of renal function. These results suggest that C4d(PTC) positivity needs to be determined at the time of biopsy even in cases of post-transplant glomerulonephritis and immunosuppression may need to be modified accordingly.
Choi
Jung
J
Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea.
Cho
Yong Mee
YM
Yang
Won Seok
WS
Park
Tae-Jin
TJ
Chang
Jai Won
JW
Park
Su-Kil
SK
D000328:Adult; D002196:Capillaries / Q000378:metabolism*; D015935:Complement C4b / Q000378:metabolism*; D005260:Female; D005922:Glomerulonephritis, IGA / Q000276:immunology*; D006084:Graft Rejection / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D007684:Kidney Tubules / Q000098:blood supply* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism*; D012189:Retrospective Studies; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d