C4d deposits in borderline rejection: an early marker for chronic renal dysfunction?

The impact of borderline rejection in renal graft remains controversial. The aim of this study was to analyze the presence of C4d deposits in peritubular capillaries and macrophage infiltration in renal biopsies with diagnosis of borderline rejection ant its effect on graft function. Thirty-one renal transplant recipients with a diagnosis of borderline rejection were included. Initial and sequential biopsies were analyzed for morphology, C4d, and macrophage staining and compared with clinical data. Initial biopsies showed 12 samples to be C4d positive, associated with a higher incidence of delayed graft function, earlier post-transplantation time, higher acute tubular necrosis score, capillaritis, and glomerular macrophage infiltration, and a lower level of tubulitis, interstitial fibrosis, and tubular atrophy compared with the C4d-negative samples. In sequential biopsies, 5 patients from the negative group turned C4d positive. Patients with ≥1 positive C4d biopsy (n = 17) showed lower renal graft function at 6 months (1.8 ± 0.8 vs 1.4 ± 0.5 mg/dL; P < .01), 1 year (2.1 ± 1 vs 1.5 ± 0.5 mg/dL; P < .01), and 2 years (2.3 ± 1.3 vs 1.5 ± 0.7 mg/dL; P < .05) of follow-up. The expression of C4d in peritubular capillaries of renal biopsies classified as borderline rejection was associated with a worse prognosis for the renal allograft.