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Clinically stable human renal allografts contain histological and RNA-based findings that correlate with deteriorating graft function.

Publication ,  Journal Article
Kirk, AD; Jacobson, LM; Heisey, DM; Radke, NF; Pirsch, JD; Sollinger, HW
Published in: Transplantation
November 27, 1999

BACKGROUND: Chronic rejection (CR) remains idiopathic, difficult to prospectively identify, and once detected, unresponsive to increased immunosuppression. We hypothesized that clinically stable human renal allografts have ongoing evidence of injury and immune activity, and that this correlates with the worsening of allograft function characteristic of CR. METHODS: The allografts of 40 stable renal allograft recipients were biopsied 2-3 years after transplantation. Biopsies were processed for histology and RNA extraction. RNA was evaluated by semi-quantitative RT-polymerase chain reaction for CD3y mRNA (a marker of T cell receptor turnover), and mRNA from cytokine genes previously shown to be transcribed during acute rejection: tumor necrosis factor-alpha, interferon-gamma, interleukin- (IL) 1beta, IL-2, IL-4, IL-6, and IL-8. Clinical parameters including urine protein and glomerular filtration rate were measured the day of biopsy. Findings were then compared with clinical outcome to establish associations between subclinical inflammation and graft dysfunction. Allograft function was measured again 2 years after biopsy and correlated with findings at the time of biopsy. RESULTS: Cytokine transcripts and histological evidence of injury were detected in more than two-thirds of stable grafts. The degree of the lymphocytic infiltrate correlated with the degree of proteinuria (P=0.034) and histological fibrosis (P=0.005). Similarly, the degree of intragraft CD3y transcription correlated with increasing proteinuria (P=0.043). IL-6 and IL-8 transcripts were also correlated with evidence of graft injury. After 2 years, those biopsies originally found to have evidence of fibrosis, tubular atrophy, or CD3gamma transcription had worsening graft function as determined by creatinine and glomerular filtration rate. CONCLUSIONS: These data demonstrate that significant injury and immune activity can be detected in patients who are stable on clinical grounds. Undetected subclinical graft injury may be a cause of chronic allograft rejection.

Duke Scholars

Published In

Transplantation

DOI

ISSN

0041-1337

Publication Date

November 27, 1999

Volume

68

Issue

10

Start / End Page

1578 / 1582

Location

United States

Related Subject Headings

  • Transplantation, Homologous
  • Surgery
  • Reproducibility of Results
  • Receptor-CD3 Complex, Antigen, T-Cell
  • RNA, Messenger
  • Kidney Transplantation
  • Immunosuppressive Agents
  • Humans
  • Glomerular Filtration Rate
  • Drug Therapy, Combination
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kirk, A. D., Jacobson, L. M., Heisey, D. M., Radke, N. F., Pirsch, J. D., & Sollinger, H. W. (1999). Clinically stable human renal allografts contain histological and RNA-based findings that correlate with deteriorating graft function. Transplantation, 68(10), 1578–1582. https://doi.org/10.1097/00007890-199911270-00024
Kirk, A. D., L. M. Jacobson, D. M. Heisey, N. F. Radke, J. D. Pirsch, and H. W. Sollinger. “Clinically stable human renal allografts contain histological and RNA-based findings that correlate with deteriorating graft function.Transplantation 68, no. 10 (November 27, 1999): 1578–82. https://doi.org/10.1097/00007890-199911270-00024.
Kirk AD, Jacobson LM, Heisey DM, Radke NF, Pirsch JD, Sollinger HW. Clinically stable human renal allografts contain histological and RNA-based findings that correlate with deteriorating graft function. Transplantation. 1999 Nov 27;68(10):1578–82.
Kirk, A. D., et al. “Clinically stable human renal allografts contain histological and RNA-based findings that correlate with deteriorating graft function.Transplantation, vol. 68, no. 10, Nov. 1999, pp. 1578–82. Pubmed, doi:10.1097/00007890-199911270-00024.
Kirk AD, Jacobson LM, Heisey DM, Radke NF, Pirsch JD, Sollinger HW. Clinically stable human renal allografts contain histological and RNA-based findings that correlate with deteriorating graft function. Transplantation. 1999 Nov 27;68(10):1578–1582.

Published In

Transplantation

DOI

ISSN

0041-1337

Publication Date

November 27, 1999

Volume

68

Issue

10

Start / End Page

1578 / 1582

Location

United States

Related Subject Headings

  • Transplantation, Homologous
  • Surgery
  • Reproducibility of Results
  • Receptor-CD3 Complex, Antigen, T-Cell
  • RNA, Messenger
  • Kidney Transplantation
  • Immunosuppressive Agents
  • Humans
  • Glomerular Filtration Rate
  • Drug Therapy, Combination