Kidney Allograft Inflammation and Fibrosis, Causes and Consequences

This study assessed the development of allograft interstitial fibrosis and inflammation (GIF+i), a histologic pattern associated with reduced graft survival. Included are 795 adults, recipients of kidney allografts from 2000 to 2006. GIF+i was diagnosed in surveillance and clinical biopsies that had no transplant glomerulopathy. With time, posttransplant increasing number of grafts showed GIF+i and these patients had reduced death-censored graft survival (HR = 4.33 (2.497.53), p < 0.0001). Development of GIF+i was related to prior acute cellular rejection (ACR), BK nephropathy (PVAN), increasing number of HLA mismatches, retransplantation and DGF. However, 46.4% of GIF+i cases had no history of ACR or PVAN. Anti-HLA antibodies at transplant did not relate to GIF+i and these patients had no increased frequency of new antibody formation posttransplant. Post-ACR biopsies showed that GIF+i developed more commonly after clinically and/or histologically more severe ACR. Graft inflammation persisted in 38.7 and 29.6% of grafts 2 and 12 months post-ACR. Twelve months post-ACR, 27.1% of biopsies developed moderate-severe GIF and 51.8% showed GIF and inflammation. Persistent inflammation and progressive GIF is often subclinical but may lead to graft failure. GIF+i can be initiated by multiple etiologies but it is often postinfectious or due to persistent cellular immune-mediated injury.