Immunohistochemical characterization of glomerular and tubulointerstitial infiltrates in renal transplant patients with chronic allograft dysfunction

Nephrol Dial Transplant. 2010 Dec;25(12):4071-7. doi: 10.1093/ndt/gfq377. Epub 2010 Jun 30.

Abstract

Background: The term chronic allograft nephropathy (CAN) was deleted in the Eighth Banff Classification and two new categories were introduced: chronic T-cell-mediated rejection (CTMR) and chronic active humoral rejection (CAHR). The aim of this study was to revise our CAN cases diagnosed in the last 4 years, analyse allograft survival rates and identify types of infiltrating cells in the different settings.

Methods: Seventy-nine patients with biopsy-proven CAN were examined and classified into four groups according to the Banff 2005 criteria: CTMR, CAHR, chronic calcineurin inhibitor toxicity (CNITOX) and interstitial fibrosis and tubular atrophy not otherwise specified (NOS). CD4, CD8, CD20, CD68, CD103, Foxp3 and IL-17 protein expression and C4d deposits were investigated.

Results: We diagnosed 20 CTMR, 13 CAHR, 28 CNITOX, and 18 NOS. Death-censored graft survival at 4 years from renal biopsy was worse in CAHR compared with the other types of chronic injury. Glomerular CD8(+) cells were increased in CTMR vs CNITOX and NOS. Interstitial CD4(+) and CD8(+) cells were increased in CTMR vs CNITOX. CD68(+) cells in glomerular and peritubular capillaries were higher in CAHR vs CNITOX, CTMR and NOS. CD103(+) cells were higher in cases with tubulitis than in those without. T regulatory and T helper 17 cells were rarely observed in the different settings.

Conclusions: Graft survival was worse in patients with CAHR. The presence of any grade transplant glomerulopathy and chronic allograft vasculopathy are poorer prognostic factors. Infiltrating CD8(+), CD103(+) and CD4(+) cells may help to differentiate CTMR from other types of chronic injury, thus improving diagnostic/prognostic features of biopsy in patients with chronic allograft dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / metabolism
  • CD4 Antigens / metabolism
  • CD8 Antigens / metabolism
  • Female
  • Forkhead Transcription Factors / metabolism
  • Graft Rejection / metabolism
  • Graft Rejection / pathology*
  • Graft Rejection / physiopathology
  • Graft Survival / physiology
  • Humans
  • Immunohistochemistry
  • Integrin alpha Chains / metabolism
  • Interleukin-17 / metabolism
  • Kidney Glomerulus / metabolism*
  • Kidney Glomerulus / pathology*
  • Kidney Glomerulus / physiopathology
  • Kidney Transplantation / pathology*
  • Kidney Transplantation / physiology
  • Kidney Tubules / metabolism*
  • Kidney Tubules / pathology*
  • Kidney Tubules / physiopathology
  • Male
  • Middle Aged
  • Retrospective Studies
  • Transplantation, Homologous

Substances

  • Antigens, CD
  • CD4 Antigens
  • CD8 Antigens
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Integrin alpha Chains
  • Interleukin-17
  • alpha E integrins