Do alloreactivity and prolonged cold ischemia cause different elementary lesions in chronic allograft nephropathy?

Am J Pathol. 2003 Jan;162(1):127-37. doi: 10.1016/S0002-9440(10)63804-7.


This study assesses the individual contributions of the nonalloreactive factor, cold ischemia (CI), and alloreactivity to late functional and structural renal graft changes, and examines the effect of the association of both factors on the progression of chronic allograft nephropathy. Lewis rats acted as receptors of kidneys from either Lewis or Fischer rats. For CI, kidneys were preserved for 5 hours. The rats were divided into four groups: Syn, syngeneic graft; SynI, syngeneic graft and CI; Allo, allogeneic graft; AlloI, allogeneic graft and CI. Renal function was assessed every 4 weeks for 24 weeks. Grafts were evaluated for acute inflammatory response at 1 week and for chronic histological damage at 24 weeks. Only when CI and allogenicity were combined did immediate posttransplant mortality occur, while survivors showed accelerated renal insufficiency that induced further mortality at 12 weeks after transplant. Solely ischemic rats developed renal insufficiency. Renal structural damage in ischemic rats was clearly tubulointerstitial, while significant vasculopathy and glomerulosclerosis appeared only in the allogeneic groups. There was increased infiltration of macrophages and expression of mRNA-transforming growth factor-beta1 in the ischemic groups, irrespective of the allogeneic background. The joint association of CI plus allogenicity significantly increased cellular infiltration at both early and late stages, aggravating tubulointerstitial and vascular damage considerably. In summary, CI is mainly responsible for tubulointerstitial damage, whereas allogenicity leads to vascular lesion. The association of both factors accelerates and aggravates the progression of experimental chronic allograft nephropathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chronic Disease
  • Cold Temperature / adverse effects*
  • Graft Rejection / immunology*
  • Immunohistochemistry
  • Inflammation / pathology
  • Ischemia / immunology
  • Ischemia / pathology*
  • Kidney / immunology
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Diseases / immunology*
  • Kidney Diseases / pathology*
  • Kidney Function Tests
  • Kidney Transplantation / adverse effects
  • Macrophages / pathology
  • Male
  • Monocytes / pathology
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Inbred Lew
  • Renal Insufficiency / immunology
  • Renal Insufficiency / pathology
  • Survival Rate
  • Time
  • Transforming Growth Factor beta / analysis
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta1
  • Transplantation, Homologous / immunology
  • Transplantation, Homologous / pathology


  • RNA, Messenger
  • Tgfb1 protein, rat
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1