Early allograft inflammation and scarring associate with graft dysfunction and poor outcomes in renal transplant...

Early histological progression that associates with delayed graft function (DGF) and its relationship to graft outcomes is less well-understood. We systematically evaluated early acute and chronic histological changes associated with DGF through serial biopsies (protocol: 3 and 12 months; for-cause) and related them to graft outcomes. 56/294 (19.04%) of our patients had DGF. DGF was associated with a progressive increase in both Banff 't' and 'i' scores from 2 weeks to 3 and 12 months with a resultant increase in T cell mediated rejection (TCMR) that was significantly greater than those with primary graft function (PGF). This increase in TCMR was predominantly sub-clinical TCMR diagnosed on protocol biopsy. Furthermore, TCMR in patients with DGF was recurrent/persistent at 12 months. Importantly, the combination of DGF and TCMR was associated with significantly worse interstitial fibrosis and tubular atrophy (IFTA) and interstitial fibrosis with inflammation (IF + 'i') as early as 3 months and worse renal function. Finally, DGF with TCMR was associated with significantly worse graft loss. In this regard, DGF without TCMR had comparable chronic histology and outcomes to PGF. Thus, DGF with TCMR (predominantly sub-clinical), represents a high-risk patient group who may benefit from early novel immunosuppression augmentation strategies to improve graft outcomes.