title: Kidney allograft survival after acute rejection, the value of follow-up biopsies.
abstract: Kidney allografts are frequently lost due to alloimmunity. Still, the impact of early acute rejection (AR) on long-term graft survival is debated. We examined this relationship focusing on graft histology post-AR and assessing specific causes of graft loss. Included are 797 recipients without anti-donor antibodies (DSA) at transplant who had 1 year protocol biopsies. 15.2% of recipients had AR diagnosed by protocol or clinical biopsies. Compared to no-AR, all histologic types of AR led to abnormal histology in 1 and 2 years protocol biopsies, including more fibrosis + inflammation (6.3% vs. 21.9%), moderate/severe fibrosis (7.7% vs. 13.5%) and transplant glomerulopathy (1.4% vs. 8.3%, all p < 0.0001). AR were associated with reduced graft survival (HR = 3.07 (1.92-4.94), p < 0.0001). However, only those AR episodes followed by abnormal histology led to reduced graft survival. Early AR related to more late alloimmune-mediated graft losses, particularly transplant glomerulopathy (31% of losses). Related to this outcome, recipients with AR were more likely to have new DSA class II 1 year posttransplant (no-AR, 11.1%; AR, 21.2%, p = 0.039). In DSA negative recipients, early AR often leads to persistent graft inflammation and increases the risk of new DSA II production. Both of these post-AR events are associated with increased risk of graft loss.
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN.
authors.forename: M
authors.initials: M
authors.lastname: El Ters
authors.forename: J P
authors.initials: JP
authors.lastname: Grande
authors.forename: M T
authors.initials: MT
authors.lastname: Keddis
authors.forename: E
authors.initials: E
authors.lastname: Rodrigo
authors.forename: B
authors.initials: B
authors.lastname: Chopra
authors.forename: P G
authors.initials: PG
authors.lastname: Dean
authors.forename: M D
authors.initials: MD
authors.lastname: Stegall
authors.forename: F G
authors.initials: FG
authors.lastname: Cosio
mesh_terms: D000328:Adult; D000368:Aged; D064591:Allografts / Q000473:pathology; D001706:Biopsy; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology*; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007668:Kidney / Q000276:immunology / Q000473:pathology / Q000502:physiology; D007674:Kidney Diseases; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D014019:Tissue Donors
chemical_list: D006680:HLA Antigens
keywords: Acute rejection; graft histology; graft survival; protocol biopsies