Activation of final complement components after kidney transplantation as a marker of delayed graft function severity

Abstract

Background. Ischaemia-reperfusion (I/R) damage is a relevant cause of delayed graft function (DGF). Complement activation is involved in experimental I/R injury, but few data are available from kidney transplant (KT) patients. We studied the dynamics of membrane attack complex (C5b-9) as a soluble fraction (SC5b-9) and the histological deposit pattern of C3b, complement Factor H (FH) and C5b-9 in DGF patients. Methods. We evaluated SC5b-9 levels in 59 recipients: 38 with immediate graft function and 21 with DGF. The SC5b-9 was measured at admission for KT and 7 days after KT. DGF-kidney biopsies (n=12) and a control group of 1-year protocol biopsies without tissue damage (n=4) were stained for C5b-9, C3b and FH. Results. SC5b-9 increased significantly in DGF patients (Day 0: 662162202mAU/L versus Day 7: 962664142 mAU/L; P=0.006), while it remained stable in non-DGF patients. Days 0-7 increase >5% was the better cut-off associated with DGF versus non-DGF patient discrimination (sensitivity=81%). In addition, SC5b-9 increase was related to DGF duration and worse graft function, and independently associated with DGF occurrence. SC5b-9, C3b and FH stains were observed in tubular epithelial cells basal membrane. DGF-kidney biopsies showed a more frequently high-intensity stain, a higher number of tubules with positive stain and larger perimeter of tubules with positive stains for SC5b-9, C3b and FH than control patients. Conclusions. Both SC5b-9 levels and SC5b-9, C3b and FH deposits in tubular epithelial cells basal membrane are highly expressed in patients experiencing DGF. SC5b-9 levels increase could be useful as a marker of DGF severity.