Kidney allograft inflammation and fibrosis, causes and consequences

Am J Transplant. 2012 May;12(5):1199-207. doi: 10.1111/j.1600-6143.2011.03911.x. Epub 2012 Jan 5.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Fibrosis / etiology*
  • Fibrosis / mortality
  • Fibrosis / pathology
  • Graft Rejection / etiology*
  • Graft Rejection / mortality
  • Graft Rejection / pathology
  • Graft Survival
  • Humans
  • Inflammation / etiology*
  • Inflammation / mortality
  • Inflammation / pathology
  • Kidney Transplantation / adverse effects*
  • Kidney Transplantation / mortality
  • Male
  • Middle Aged
  • Nephritis / etiology*
  • Nephritis / mortality
  • Nephritis / pathology
  • Prognosis
  • Survival Rate
  • Transplantation, Homologous