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 (2.49-7.53), 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.
Division of Nephrology and Hypertension, Department of Internal Medicine, and William von Liebig Transplant Center, Mayo Clinic, Rochester, MN, USA.
M
M
Gago
L D
LD
Cornell
W K
WK
Kremers
M D
MD
Stegall
F G
FG
Cosio
D000328:Adult; D005260:Female; D005355:Fibrosis / Q000209:etiology* / Q000401:mortality / Q000473:pathology; D006084:Graft Rejection / Q000209:etiology* / Q000401:mortality / Q000473:pathology; D006085:Graft Survival; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000401:mortality / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009393:Nephritis / Q000209:etiology* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D015996:Survival Rate; D014184:Transplantation, Homologous