Indication Biopsies Ten Years after Renal Transplant Frequently Show Antibody-Mediated Mechanisms of Allograft Injury

Abstract

Long-term kidney allograft survival is greatly affected by chronic rejection that occurs through different pathways, mainly antibody-mediated and T cell-mediated. Previously, we demonstrated that 60% of the indication biopsies in patients clinically classified as chronic allograft nephropathy (CAN) were C4d-positive. Mechanistic classification of chronic allograft dysfunction (CAD) is available according to the Banff Classification. In order to evaluate the CAD biopsy findings in the very long-term follow-up, we retrieved indication biopsies obtained 10 or more years after kidney transplantation when C4d was routinely introduced at our center (06/2006) until 7/2011. 387 patients had 10 or more years of kidney transplant during this period. Among them, 43 patients (11.1%) had an indication biopsy after 10 years. The biopsies were blindly reviewed by two nephropathologists. Antibody-mediated rejection (AMR) was a very frequent finding (n=14, 32.5%), being 10 (23.2%) chronic active antibody-mediated rejection (CAMR) and 4 (9.3%) “late” acute antibody-mediated rejection (LAAMR). The LAAMR cases did not show any sign of chronicity, even when analyzed by electron microscopy. Tubular atrophy and interstitial fibrosis of undetermined origin (IFTA) was equally frequent (n=14, 32.5%), followed by de novo/relapsing glomerulopathies (n=5, 11.6%), C4d-negative transplant glomerulopathy (TG) (n=3, 7.0%), acute T cell-mediated rejection (n=1, 2.3%), borderline changes (n=1, 2.3%), chronic active T cell-mediated rejection (n=1, 2.3%), acute tubular necrosis (n=1, 2.3%), and other finding (n=3, 7.0%). The three TG C4d-negative cases were HCV-positive in the serum and one had also circulating donor-speci fi c antibodies (DSAs). This study is one of the rare available in literature that approaches a cohort of indication biopsies performed 10 or more years post-transplant and keeps showing the high frequency (one-third) of AM mechanism impacting in long-term graft survival.