Chronic Rejection Grading

Rejection Rejection Rejection Rejection Rejection Rejection Rejection Rejection Rejection Rejection Rejection

Obliterative Arteriopathy or Graft Vascular Disease(GVD)

Chronic rejection is the single most significant obstacle to long term organ allograft survival. It similar manifests in all vascularized solid organ allografts as obliterative arteriopathy or graft vascular disease(GVD), interstitial fibrosis and atrophy of parenchymal elements that eventually result in allograft failure. Chronic rejection usually has an insidious onset, although abrupt arterial damage from a severe acute rejection can manifest similar arterial pathology. The principal histopathological finding in GVD is concentric narrowing of the arterial lumen because of fibrointimal hyperplasia. Veins are much less frequently and less severely involved.

Although GVD or OA is similar to atherosclerosis seen in the general population, there also are distinct differences. A comparison of the two is shown below:

Table 1. Comparison of GVD and atherosclerosis in the general population.
Histopathological FindingGraft Vascular Disease Atherosclerosis
Epicardial Coronary arteriesInvolved Preferentially involved
Penetrating intra-myocardial arteriesInvolved Not involved
EndotheliumOften intact, but hypertrophied Usually intact, hypertrophy not as obvious as GVD
Myointimal proliferation and lumenal narrowing Yes, concentricYes, eccentric
Intimal lipid and cholesterol deposits UncommonCommon
Intimal inflammationVariable Variable
Elastic laminaFocally disrupted Focally disrupted
MediaThinned in late stage Thinned in late stage
Medial inflammationVariable Variable
Adventitial InflammationCommon Variable

GVD is thought to be due to direct immunological injury to the allogeneic arterial endothelium, which disrupts intimal homeostasis. In turn, the injury is thought to trigger a cytokine and growth-factor-driven arterial repair response that results in lumenal narrowing. Several excellent reviews of this subject of this subject are suggested (1-7).

Selected References

  1. Hayry P, Isoniemi H, Yilmaz S, et al. Chronic allograft rejection. Immunol Rev 1993;134:33-81.
  2. Adams DH, Russell ME, Hancock WW, et al. Chronic rejection in experimental cardiac transplantation: studies in the Lewis-F344 model. [Review]. Immunol Rev 1993;134:5-19.
  3. Billingham ME. - Pathology and etiology of chronic rejection of the heart. Clin Transplant 1994;8(3 Pt 2): 289-292.
  4. Demetris AJ, Zerbe T, Banner B. Morphology of solid organ allograft arteriopathy: identification of proliferating intimal cell populations. Transplant Proc 1989;21(4):3667-3669.
  5. Ewel CH, Foegh ML. - Chronic graft rejection: accelerated transplant arteriosclerosis. [Review]. Immunol Rev 1993;134:21-31.
  6. Paul LC, Davidoff A, Benediktsson H. Cardiac allograft atherosclerosis in the rat. The effect of histocompatibility factors, cyclosporine, and an angiotensin-converting enzyme inhibitor. Transplantation 1994;57(12):1767-1772.
  7. Matas AJ, Burke JF, Jr., DeVault GA, Jr., Monaco A, Pirsch JD. - Chronic rejection. [Review]. J Am Soc Nephrol 1994;4(8 Suppl): S23-S29.

Last Modified: Mon Aug 24 8:00:00 EDT 2009