The impact of C4d and microvascular inflammation before we knew them

It is important to identify prognostically important morphologic criteria in post-transplant management to tailor therapy and improve outcomes. Therefore, using biopsies carried out for cause <1-yr post-transplant, from an era when C4d staining and microvascular inflammation (MVI) were not clinically utilized, we studied the importance of C4d and MVI on graft survival. Snap-frozen first renal allograft biopsy specimens (done for cause) in the first post-transplant year from 1996 to 2001 were stained/examined for C4d, and pathology re-examined by a separate blinded pathologist. Graft outcomes in patients with and without MVI and/or C4d were compared. Of 128 patients, 39 (30.5%) biopsies were C4d+ and 89 (69.5%) were C4d-; 67 (52.3%) had no MVI (MVI-) while 61 (47.7%) had glomerulitis, peritubular capillaritis, or both (MVI+). There were no significant demographic differences between MVI+ and MVI- patients. A greater proportion of C4d+ biopsies was MVI+ (67%) than MVI- (33%; p = 0.004). C4d positivity had no impact on death-censored graft survival (DCGS). In contrast DCGS was worse in MVI+ than MVI- regardless of presence/absence of C4d (p = 0.005). In biopsies for cause carried out <1-yr post-transplant, MVI is associated with decreased DCGS, independent of the presence of C4d.