Fibrosis with inflammation at one year predicts transplant functional decline.

Department of Surgery, Division of Transplantation Surgery, Mayo Clinic, Rochester, Minnesota, USA.
Journal of the American Society of Nephrology (Impact Factor: 9.47). 11/2010; 21(11):1987-97. DOI: 10.1681/ASN.2010010049
Source: PubMed

ABSTRACT Lack of knowledge regarding specific causes for late loss of kidney transplants hampers improvements in long-term allograft survival. Kidney transplants with both interstitial fibrosis and subclinical inflammation but not fibrosis alone after 1 year have reduced survival. This study tested whether fibrosis with inflammation at 1 year associates with decline of renal function in a low-risk cohort and characterized the nature of the inflammation. We studied 151 living-donor, tacrolimus/mycophenolate-treated recipients without overt risk factors for reduced graft survival. Transplants with normal histology (n = 86) or fibrosis alone (n = 45) on 1-year protocol biopsy had stable renal function between 1 and 5 years, whereas those with both fibrosis and inflammation (n = 20) exhibited a decline in GFR and reduced graft survival. Immunohistochemistry confirmed increased interstitial T cells and macrophages/dendritic cells in the group with both fibrosis and inflammation, and there was increased expression of transcripts related to innate and cognate immunity. Pathway- and pathologic process-specific analyses of microarray profiles revealed that potentially damaging immunologic activities were enriched among the overexpressed transcripts (e.g., Toll-like receptor signaling, antigen presentation/dendritic cell maturation, IFN-γ-inducible response, cytotoxic T lymphocyte-associated and acute rejection-associated genes). Therefore, the combination of fibrosis and inflammation in 1-year protocol biopsies associates with reduced graft function and survival as well as a rejection-like gene expression signature, even among recipients with no clinical risk factors for poor outcomes. Early interventions aimed at altering rejection-like inflammation may improve long-term survival of kidney allografts.

  • Nature Reviews Nephrology 01/2011; 7(1):3. DOI:10.1038/nrneph.2010.161 · 8.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In the last decade, gene expression studies of kidney transplants provided an opportunity to better understand the development and regulation of kidney graft rejection. This review outlines the progress in the definition of biomarkers of rejection and, above all, concentrates on studies of the molecular phenotype of rejection. This phenotype, rather than morphological characterization, may be critical for assessing the ongoing processes in the graft and for the outcome prediction. Copyright (C) 2011 S. Karger AG, Basel
    Kidney and Blood Pressure Research 01/2011; 34(4):291-8. DOI:10.1159/000326895 · 1.82 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: There is a critical need for biomarkers for early diagnosis, treatment response, and surrogate end point and outcome prediction in organ transplantation, leading to a tailored and individualized treatment. Genomic and proteomic platforms have provided multiple promising new biomarkers during the last few years. However, there is still no routine application of any of these markers in clinical transplantation. This article will discuss the existing gap between biomarker discovery and clinical application in the kidney transplant setting. Approaches to implementing biomarker monitoring into clinical practice will also be discussed.
    Expert Review of Molecular Diagnostics 03/2011; 11(2):183-96. DOI:10.1586/erm.10.119 · 4.27 Impact Factor


Available from