We and others have shown late DCGF is due to ongoing, most often immune, injury. Though there is general agreement that antibody-mediated injury is a common cause of late DCGF, the impact of cell-mediated immunity remains controversial. In this prospective, multicenter study, 559 pts underwent for-cause biopsies 7.9±5.8 years post-txp for new-onset graft dysfunction or proteinuria, with 235 having both central DSA determination, and biopsy (bx) read by a blinded pathologist according to 2007 Banff criteria. MIA was characterized by quantitative g (glomerulitis) and ptc (peritubular capillaritis) scores; other inflammation by i (interstitial) and t (tubulitis) scores. Pts with DSA, C4d, or both were more likely to have g (p=0.04) and ptc (p<0.001) scores ≥ 1. By univariate analysis, DSA (HR=2.9), C4d (HR=3.1), both DSA/C4d (HR=4.3), g (HR≥1.8), ptc (HR≥2.4), combined g+ptc score (HR≥2.7), i (HR≥1.5), and t (HR≥1.8) were all associated with increased risk for DCGF, as were time after transplantation and serum creatinine at bx. Multivariate analysis demonstrated a significant, independent impact of DSA/C4d classification, MIA, and i, but not t, scores on risk for DCGF.

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