Kidney nontumor
Diseases of renal allograft
Chronic rejection

Topic Completed: 3 December 2012

Revised: 11 March 2019

Copyright: 2002-2019,, Inc.

PubMed Search: Kidney transplantation chronic rejection [title]

Nikhil Sangle, M.D.
Page views in 2018: 1,507
Page views in 2019 to date: 1,105
Cite this page: Sangle N. Chronic rejection. website. Accessed October 18th, 2019.
Definition / general
  • Also called chronic allograft nephropathy, interstitial fibrosis and tubular atrophy not otherwise specified
  • Irreversible end stage of repeated episodes of acute vascular or interstitial rejection
  • Occurs months to years after transplantation, independent of acute rejection and specific disease
  • Incidence of 55% after 8 years posttransplant in one study (Nephrol Dial Transplant 2011;26:3750)
  • Most common cause of graft failure after 6 - 12 months
  • Transplant arteriopathy / capillaropathy and glomerulopathy are induced by alloantigens - systematic assessment of longitudinal changes in alloantibody levels can identify patients at greater risk (Kidney Int 2011;79:1131)
  • Inflammation (due to various causes) and tissue remodeling may induce autoimmune responses against self antigens, leading to chronic rejection (Discov Med 2010;9:229)
Gross images

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Enlarged kidney with surface hemorrhage

Microscopic (histologic) description
  • Chronic transplant nephropathy: non specific sclerosing changes (no lesions indicative of immunologic injury, thus a diagnosis of exclusion)
  • Resembles nephrosclerosis
  • Severe obliterative fibrointimal proliferation or mucoid widening of intima
  • Reduplication or disruption of elastic lamina and irregular fibrosis of media
  • Variable distribution of vascular lesions; also occasional small thrombi
  • Atrophic tubules, diffusely scarred interstitium
  • Glomerulosclerosis with ischemic glomerular capillary collapse and thickened capillary walls
  • Transplant capillaropathy: peritubular capillary profile with 7+ circumferential basement membrane layers or 3 profiles with 5 - 6 circumferential layers; these findings are specific (except for obstructive uropathy or thrombotic microangiopathy) and sensitive (present in 80%) for chronic rejection; may be due to repeated episodes of endothelial cell damage or death and regeneration
Microscopic (histologic) images

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Various images

Immunofluorescence description
  • Negative, occasional linear or granular deposition of IgM, IgG or complement
Electron microscopy description
  • Thickened capillary walls due to widening of subendothelial space or mesangial interposition
  • Electron microscopy better than light microscopy to identify microvascular changes (Mod Pathol 2001;14:1200)
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